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To compare the effectiveness and safety of a single injection of subconjunctival triamcinolone acetonide (TA) with that of postoperative topical prednisolone acetate (PA) with and without nonsteroidal anti-inflammatory drugs (NSAIDs) for cataract surgery prophylaxis. Retrospective, comparative effectiveness cohort study. Patients at Kaiser Permanente Northern California from 2018 through 2021. Exposure groups included topical PA with or without NSAID and subconjunctival injection of TA (Kenalog; Bristol-Myers-Squibb) 10 mg/ml or 40 mg/ml in a low dose (1.0–3.0 mg) or high dose (3.1–5.0 mg). The adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of postoperative macular edema (ME) and iritis diagnoses 15 to 120 days after surgery (effectiveness measures) and a glaucoma-related event (safety measure) between 15 days and 1 year after surgery. Of 69 832 eligible patient-eyes, postoperative ME, iritis, and a glaucoma-related event occurred on average in 1.3%, 0.8%, and 3.4% of eyes in the topical groups and 0.8%, 0.5%, and 2.8% of eyes in the injection groups, respectively. In multivariable analysis, compared with the PA reference group, the PA plus NSAID group had a lower OR of ME (OR, 0.88; 95% CI, 0.74–1.04; P = 0.135). and all injection groups had even lower odds, with the high-dose TA 10-mg/ml group reaching statistical significance (OR, 0.64; 95% CI, 0.43–0.97; P = 0.033). A trend of lower odds of a postoperative iritis diagnosis was noted in the high-strength (40 mg/ml) groups. For postoperative glaucoma-related events, compared with PA, the TA 10-mg/ml low-dose group showed lower odds (OR, 0.69; 95% CI, 0.55–0.86; P = 0.001), the TA 10-mg/ml high-dose group showed similar odds (OR, 0.90; 95% CI, 0.70–1.15; P = 0.40), and the TA 40-mg/ml low-dose and high-dose groups showed higher odds of an event occurring (OR, 1.46 [95% CI, 0.98–2.18; P = 0.062] and OR, 2.14 [95% CI, 1.36–3.37; P = 0.001], respectively). The TA 10-mg/ml high-dose (4 mg) group was associated with a lower risk of postoperative ME and a similar risk of glaucoma-related events compared with the topical groups. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

The permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz diffusion cell. The delivery systems composition and ethyl cellulose (EC) backing layer, on drug permeability, were assessed. Three TA-loaded films were tested; hydroxypropyl methylcellulose (HPMC K4M; bilayer [F1] and monolayer), HPMC K4M/Polyvinylpyrrolidone (PVP): 90/10 [F2], and HPMC K15M film [F3]. All films contained propylene glycol (PG-plasticiser). TA solution alone was used as a control. TA permeability via a Permeapad™ barrier, simulating buccal mucosa, was assessed over 8 h using a Franz diffusion cell. TA permeated into the receptor compartment, released in the donor compartment, and located on/within the Permeapad™ barrier were analysed using UV-spectrophotometer. 45.7 % drug retention within the Permeapad™ barrier was delivered from F1 (highest). F1, F2, and F3 significantly improved the TA's permeability through Permeapad™, compared to TA solution alone (e.g., 8.5 % TA-solution, 21.5 %-F1), attributed to the synergy effect of HPMC and propylene glycol acting as penetration enhancers. F1 displayed a significant increase in drug permeability (receptor compartment; 21.5 %) compared to F3 (17.0 %). PVP significantly enhanced drug permeability (27.5 %). Impermeable EC backing layer controlled unidirectional drug release and reduced drug loss into the donor compartment (e.g., ∼28 % for monolayer film to ∼10 % for bilayer film, F1). The mucoadhesive films demonstrated improved TA permeability via Permeapad™. The findings suggest that these bilayer mucoadhesive films, particularly F1, hold promise for the effective topical treatment of oral mucosa disorders, such as recurrent aphthous stomatitis and oral lichen planus. • Bilayer mucoadhesive buccal films to enhance TA permeability through Permeapad™. • F1-highest TA retention in Permeapad™ for potentially treating oral mucosa disorders. • EC backing layer minimized the loss of TA into the donor compartment. • The biomimetic membrane, Permeapad™ was successfully used for TA permeation assay. • Franz cell was used to predict the amount of drug permeating across Permeapad™. [ABSTRACT FROM AUTHOR]

To review the evidence on the effectiveness and complications of periocular and intraocular corticosteroid therapies for noninfectious uveitic macular edema. A literature search of the PubMed database was conducted last in December 2021 and a post-assessment search was conducted in March 2023. The searches were limited to articles published in English and no date restrictions were imposed. The combined searches yielded 739 citations; 53 articles were selected for inclusion because the studies (1) evaluated periocular corticosteroid injection, intraocular corticosteroid injection or implant, suprachoroidal corticosteroid injection, or a combination thereof for uveitic macular edema; (2) had outcomes that included visual acuity (VA) or macular edema assessed clinically or imaged by OCT or fluorescein angiography; and (3) included more than 20 patients. This assessment reviewed 23 articles that provided level I or level II evidence from 18 studies on the use of periocular, suprachoroidal, and intravitreal triamcinolone acetonide injections and intravitreal dexamethasone and fluocinolone acetonide implants or inserts in noninfectious uveitic macular edema. These reports consistently demonstrated that all investigated periocular and intraocular corticosteroid therapies improved VA, macular structure, or both. One comparative study showed that intravitreal triamcinolone acetonide injection and the dexamethasone intravitreal implant had effectiveness superior to that of periocular triamcinolone acetonide injection for these outcomes. As a group, the studies highlighted the potential for these therapies to elevate intraocular pressure and to accelerate cataract formation. The published literature provides high-quality evidence that periocular and intraocular corticosteroid therapies are effective and safe for the treatment of noninfectious uveitic macular edema. However, information on the relative effectiveness and complication rates across the different therapies is limited. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Recurrent aphthous stomatitis (RAS) is a painful disorder that commonly appears as ulcers on the oral mucosa, lasting ∼two weeks (minor) to months (major and herpetiform). Current treatment often necessitates the use of topical steroids in the form of pastes, mouthwashes, or gels, but these forms are often ineffective due to inadequate drug contact time with the ulcers. In this study, the performance of novel bilayer mucoadhesive buccal films loaded with triamcinolone acetonide (TA) has been evaluated for targeted drug delivery. Experimental mucoadhesive films of hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), and polyvinyl pyrrolidone (PVP) were prepared by the solvent casting method, and ethyl cellulose (EC) was applied as the backing layer. The films were characterized for their physical properties, including swelling index (SI), folding endurance, adhesion force with porcine buccal mucosa, residence time and in-vitro drug release. The data showed that the films were flexible with folding endurance> 300 times. With porcine buccal mucosa i) suitable adhesion forces were obtained (between 2.72 and 4.03 N), ii) residence times of> 24 h, and iii) surface pH between 6.8 and 7.1 indicating they would be non-irritant. All films released 100% TA over 6 h, but with varying profiles. The release of TA (over 6 h) from PVP-free films followed Fickian diffusion kinetics (diffusion-controlled release of drug), whereas the mechanism of release from PVP-containing films was found to be a superposition of diffusion-controlled and erosion-controlled release (anomalous). The developed films hold great promise for potentially treating RAS and other oral conditions. • Oral bilayer-mucoadhesive films with triamcinolone acetonide for treating RAS. • Films presented with appropriate characteristics for oral mucosal application. • Polymer films with improved residence time and adhesion force on porcine mucosa. • Sustained drug release (6 h) from films with Fickian and/or anomalous diffusion. • HPMC films show potential for oral, topical triamcinolone acetonide delivery. [ABSTRACT FROM AUTHOR]

[Display omitted] The objectives of this study were to expand and implement a Computational Fluid Dynamics (CFD)-Dissolution, Absorption and Clearance (DAC)-Pharmacokinetics (PK) multi-physics modeling framework for simulating the transport of suspension-based nasal corticosteroid sprays. The mean CFD-predicted peak plasma concentration (C max) and area under the curve (AUC) of the plasma concentration–time profile, based on three representative nasal airway models (capturing low, medium and high posterior spray deposition), were within one standard deviation of available in vivo PK data for a representative corticosteroid drug (triamcinolone acetonide). The relative differences in mean C max between predictions and in vivo data for low dose (110 µg) and high dose (220 µg) cases were 27.8% and 10.1%, respectively. The models confirmed the dose-dependent dissolution-limited behavior of nasally delivered triamcinolone acetonide observed in available in vivo data. The total uptake from the nasal cavity decreased from 68.3% to 51.3% for the medium deposition model as dose was increased from 110 to 220 µg due to concentration-limited dissolution. The modeling framework is envisioned to facilitate faster development and testing of generic locally acting suspension nasal spray products due to its ability to predict the impact of differences in spray characteristics and patient use parameters on systemic PK. [ABSTRACT FROM AUTHOR]

Objectives: Suprachoroidal injection of triamcinolone acetonide is the first Food and Drug Administration-approved treatment for macular edema associated with uveitis. A cost-effectiveness analysis was performed comparing this treatment with best supportive care (BSC) for the management of this indication from US Medicare and commercial payer perspectives.Methods: A patient-level simulation was developed per the patient characteristics and changes in best-corrected visual acuity letter scores observed in a phase III study of triamcinolone acetonide (PEACHTREE). The wholesale acquisition cost of triamcinolone acetonide was $1650/injection; suprachoroidal injection cost was assumed at $200/injection. Healthcare costs were informed by a US claims-based analysis. Mortality risk associated with severe vision loss and blindness was modeled by applying a hazard ratio to all-cause mortality rates of the US general population. Health-related quality of life weights, obtained from a regression model fitted to the Visual Function Questionnaire-25 data from PEACHTREE, were applied based on the best-corrected visual acuity scores of both eyes. Costs (2020 US dollar) and benefits were discounted at 3% annually. Incremental cost-effectiveness ratios were estimated over a 10-year horizon.Results: In the base-case, the incremental cost-effectiveness ratio comparing triamcinolone acetonide with BSC was $28 479 per quality-adjusted life-year gained. The wholesale acquisition cost for triamcinolone acetonide for suprachoroidal use was ∼68%, ∼56%, and ∼27% below the willingness-to-pay thresholds of $150 000, $100 000, and $50 000 per quality-adjusted life-year gained, respectively. Results were robust in sensitivity and scenario analyses.Conclusions: Triamcinolone acetonide for suprachoroidal use is cost-effective compared with BSC for patients with macular edema associated with uveitis. [ABSTRACT FROM AUTHOR]

Uveitis is among the leading causes of visual loss in the working age population. In noninfectious uveitis, corticosteroids are the first line therapy. We sought to review systematically the evidence regarding the regional corticosteroid delivery modalities in the treatment of noninfectious uveitis. A 5-database search (Pubmed, ISI Web of Science, Cochrane, ClinicalTrials.gov, and Scopus) was performed from inception to February, 2021. Nineteen studies with a total of 1,935 eyes of 1,753 patients were selected from 8,922 abstracts retrieved by the initial search. The most frequently compared regimens were intravitreal triamcinolone acetonide injection and orbital floor triamcinolone acetonide injection (2 studies), intravitreal triamcinolone acetonide injection and posterior sub-Tenon triamcinolone acetonide injection (2 studies), and posterior sub-Tenon triamcinolone acetonide injection with the intravitreal dexamethasone implant (2 studies). Our results show that the intravitreal injection of corticosteroids is more effective, but is associated with more adverse events, than periocular injection. Some evidence supports the use of subconjunctival triamcinolone acetonide over intravitreal/periocular triamcinolone acetonide. Moreover, the overall results of 0.59 mg dosage of the intravitreal fluocinolone acetonide implant were superior to those from the 2.1 mg dose. The evidence, however, is not robust, and further studies with standardized outcomes are warranted. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effectiveness of triamcinolone acetonide in suppressing inflammation after blepharoptosis surgery. The study was designed as prospective, randomized, two medical centers' clinical trial. Thirty-two patients with involutional blepharoptosis of the same degree in both eyelids underwent bilateral transcutaneous levator advancement. At the end of the surgery, 4 mg/0.1 ml of triamcinolone acetonide was injected into a randomly selected upper eyelid. The fellow eyelid was not injected and was used as control. Facial photographs were taken on day 1, week 1, month 1, and month 3, and the degree of inflammation, the margin reflex distance 1 (MRD-1), and levator function (LF) between the two eyelids of each patient were compared. The primary outcome was the selection of the less inflamed eyelid decided by the majority of three individuals unrelated to the study. MRD-1 and LF were analyzed for secondary outcomes. As a result, the injected eyelid was judged to be the less inflamed eyelid in all cases. The MRD-1 in the postoperative period less than 1 month was significantly larger in the injected eyelids than the control eyelids (P <0.03). The postsurgical MRD-1 at month 3, the postsurgical LF at all postsurgical examination times were not statistically different. Adverse complications by the injection, including ptosis, levator dysfunction, increase of the intraocular pressure, and visual disturbance were not observed. In conclusion, a triamcinolone acetonide injection after ptosis surgery is both safe and effective in reducing the early postsurgical inflammation and helpful in an earlier return to a daily routine for the patients. [ABSTRACT FROM AUTHOR]

[Display omitted] Intratympanically applied treatments are of increasing interest to the otologic community to treat sudden sensorineural hearing loss or vestibular disorders but also to deliver gene therapy agents, or biologics to the inner ear. Further diversion from the middle ear and perilymph to blood circulation and cerebrospinal fluid via the cochlear aqueduct are one of the limiting factors and so far not understood well enough. In this study, intratympanically applied triamcinolone acetonide was determined in cerebrospinal fluid. Additionally, perilymph was sampled through the round window membrane as well as at the lateral semicircular canal to determine drug levels. Of the twenty-one included patients, triamcinolone acetonide was quantifiable in cerebrospinal fluid in 43% at very low levels (range 0 ng/ml–6.2 ng/ml) which did not correlate with perilymph levels. Drug levels at the two different perilymph sampling sites were within a range of 13.5 ng/ml to 1180.0 ng/ml. Results suggest an equal distribution of triamcinolone acetonide to semicircular canals, which might support the use of triamcinolone acetonide as a treatment option for vestibular pathologies such as Menièrés disease. On the other hand, the distribution to cerebrospinal fluid might be limiting current approaches in gene therapy where a central distribution is unwanted. [ABSTRACT FROM AUTHOR]

Background: The objective of this systematic review and meta-analysis was to examine the effect and safety of multimodal cocktail protocols implemented with or without glucocorticoids on periarticular infiltration analgesia (PIA) in patients undergoing total knee arthroplasty (TKA).Methods: We comprehensively searched the PubMed, Medline, Embase, and Cochrane Library databases up to November 2020 for randomized controlled trials on glucocorticoids as a component of the cocktail protocol used in PIA for patients with TKA.Results: Our meta-analysis included 11 randomized controlled trial studies with 1051 primary TKAs (930 patients). Visual analog scale scores at postoperative day (POD) 1 and POD 2 in the glucocorticoid groups were significantly lower than those in the control group (95% CI [-1.01--0.10], P = .02; 95% CI [-0.51--0.13], P = .001). Furthermore, the glucocorticoid group was associated with a statistically significant improvement in the range of motion at POD 1 (95% CI [3.20-8.05] P < .00001), reduction in total morphine consumption at 24 hours, and lower levels of C-reactive protein on POD 2/3 compared with the control group. However, neither the length of hospital stays nor the long-term Knee Society Knee Score showed any differences between the two groups. In addition, the results of subgroup analyses favored triamcinolone acetonide over betamethasone, methylprednisolone, and dexamethasone regarding the postoperative visual analog scale scores and range of motion.Conclusion: Glucocorticoid supplementation in PIA is effective and does not increase complications or side effects for patients with either unilateral or bilateral TKA. Moreover, triamcinolone acetonide could be recommended in multimodal cocktail protocols for glucocorticoid supplementation. [ABSTRACT FROM AUTHOR]

Background: Triamcinolone acetonide (TAC) is widely used for hypertrophic scars and keloids; however, TAC has variable efficacy and safety in different individuals.Purpose: To evaluate the efficacy and safety of intralesional TAC for treatment of hypertrophic scars and keloids.Data Sources: Searches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov prior to 25 March 2020.Study Selection: Randomized controlled trials in English that compared TAC with a placebo or other medications that are commonly used for intralesional injection in hypertrophic scars and keloids.Data Extraction: Primary outcomes were reduction in scar height, vascularity, pliability, pigmentation, total scores on the Vancouver Scar Scale (VSS) or patient and observer scar assessment scale (POSAS), telangiectasia, and skin atrophy. Secondary outcomes included overall scar improvement.Data Synthesis: Fifteen trials met the inclusion criteria. In the short term, TAC was associated with a significant improvement in vascularity (MD: -0.22, 95% CI: -0.42 to -0.02) and pliability (MD: -0.25, 95% CI: -0.44 to -0.06) compared to verapamil. In the medium term, compared to TAC, 5-FU showed a significant improvement in scar height (SMD: 0.95, 95% CI: 0.15-1.75), while TAC led to a significant improvement in vascularity compared to 5-FU (MD: -0.45, 95% CI: -0.76 to -0.14). Compared to TAC, TAC+5-FU showed a significant improvement in pliability (SMD: 0.98, 95% CI: 0.17-1.78) and pigmentation (MD: 0.45, 95% CI: 0.12-0.78). Botulinum toxin type A resulted in significantly better pliability (SMD: 1.99, 95% CI: 0.98-3.00) compared to TAC. In the long term, compared to TAC, 5-FU led to a significant improvement in scar height (MD: 0.55, 95% CI: 0.17-0.93), but significantly less vascularity (MD: -0.35, 95% CI: -0.65 to -0.05). Compared to TAC, TAC+5-FU produced a significant improvement in scar height (MD: 1.50, 95% CI: 1.12-1.88), pliability (MD: 0.45, 95% CI: 0.10-0.80), and pigmentation (MD: 0.55, 95% CI: 0.24-0.86).Conclusion: TAC may be beneficial for the short-term treatment of hypertrophic scars and keloids; however, 5-FU, 5-FU+TAC, and verapamil may produce superior results for medium- and long-term treatments. TAC injections at concentrations of 20 mg/ml or 40 mg/ml are more likely to result in skin atrophy compared to 5-FU or verapamil, and are more likely to cause telangiectasia than 5-FU, 5-FU+TAC, or bleomycin. [ABSTRACT FROM AUTHOR]

Inflammation and neovascularization are key pathological events in human age-related macular degeneration (AMD). Activated microglia/macrophages (mi/ma) and retinal pigmented epithelium (RPE) play an active role in every stage of disease progression. Systemic therapies that can target these cells and address both inflammation and neovascularization will broaden the impact of existing therapies and potentially open new avenues for early AMD where there are no viable therapies. Utilizing a clinically relevant rat model of AMD that mirrors many aspects that of human AMD pathological events, we show that systemic hydroxyl-terminated polyamidoamine dendrimer-triamcinolone acetonide conjugate (D-TA) is selectively taken up by the injured mi/ma and RPE (without the need for targeting ligands). D-TA suppresses choroidal neovascularization significantly (by >80%, >50-fold better than free drug), attenuates inflammation in the choroid and retina, by limiting macrophage infiltration in the pathological area, significantly suppressing pro-inflammatory cytokines and pro-angiogenic factors, with minimal side effects to healthy ocular tissue and other organs. In ex vivo studies on human postmortem diabetic eyes, the dendrimer is also taken up into choroidal macrophages. These results suggest that the systemic hydroxyl dendrimer-drugs can offer new avenues for therapies in treating early/dry AMD and late/neovascular AMD alone, or in combination with current anti-VEGF therapies. This hydroxyl dendrimer platform but conjugated to a different drug is undergoing clinical trials for severe COVID-19, potentially paving the way for faster clinical translation of similar compounds for ocular and retinal disorders. [Display omitted] • In AMD, dendrimer-TA targets activated macrophages/microglia in choroid/retina and RPE. • Systemic D-TA therapy profoundly suppresses CNV, and retinal/choroidal inflammation. • Systemic therapies can enable transformative early treatments for AMD and DR. [ABSTRACT FROM AUTHOR]

Contact lenses (CLs) constitute an advantageous platform for the topical release of corticosteroids due to their prolonged contact with the eye. However, the lipophilic nature of corticosteroids hampers CLs' ability to release therapeutic amounts. Two approaches to improve loading and release of triamcinolone acetonide (TA) from poly(2-hydroxyethyl methacrylate)-based hydrogels were investigated: adding 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to the monomers solution before polymerization (HEMA/i-CD) and an hydrogels' post-treatment with HP-β-CD (HEMA/p-CD). The effect of HP-β-CD and sterilization by high hydrostatic pressure (HHP) on the hydrogel properties (water content, oxygen and ion permeability, roughness, transmittance, and stiffness) was evaluated. The HEMA/i-CD hydrogels had stronger affinity for TA, sustaining its release for one day. HHP sterilization promoted the formation of cyclodextrin-TA complexes within the hydrogels, improving their drug-loading capacity »60 %. Cytotoxicity and irritability tests confirmed the safety of the therapeutic CLs. TA released from the hydrogels permeated through ocular tissues ex vivo and showed anti-inflammatory activity. Finally, a previously validated mathematical model was used to estimate the ability of the TA-loaded CLs to deliver therapeutic drug concentrations to the posterior part of the eye. Overall, HP-β-CD-containing CLs are promising candidates for the topical ocular application of TA as an alternative delivery system to intraocular injections. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Developing a novel electrochemical sensor for detection of triamcinolone acetonide. • Electrochemical sensor based on Ag nanoparticles and a reduced graphene. • A promising sensor for practical applications in sports and anti-doping regulations. The use of performance-enhancing drugs in sports is a major concern for athletes, coaches, and sports organizations. To address this issue, researchers have been developing advanced doping agent surveillance techniques, including the use of sensors for detecting prohibited substances in athletes' samples. The aim of this work was to create Ag nanoparticles and a reduced graphene oxide paste electrode (Ag-rGOPE) that could be used as an electrochemical sensor to measure the amounts of triamcinolone acetonide (TAA) in athlete blood serum samples for the purpose of detecting doping. The combination of Ag nanoparticles on rGO nanosheets was validated by the findings of structural investigations. The potential of Ag-rGOPE as a promising substitute for the analysis of TAA in actual samples was underlined by the electrochemical investigations. Ag-rGOPE was reported to have a sensitivity value of 0.67522 μA/μM, a linear range of 10 to 300 μM, and a limit of detection of 0.005 μM. High electrochemical reactivity, a broad linear range, and a small limit of detection were all characteristics of the Ag-rGOPE toward TAA. With considerable recovery values (above 96.00 %) and acceptable precision (RSD less than 4.37 %), the sensor showed outstanding performance for detecting TAA in serum samples. Overall, Ag-rGOPE demonstrated potential as an electrochemical sensor for measuring TAA levels in athlete serum samples that is both dependable and accurate. [ABSTRACT FROM AUTHOR]

[Display omitted] Inflammation of the posterior segment of the eye is a severe condition and hard to cure as delivery of drugs to the inflammation site is inefficient. Currently, the primary treatment approach is ocular surgery or invasive ocular injections. Herein, we designed and developed a topically self nano-emulsifying drug delivery system (SNEDDs) to deliver triamcinolone acetonide (TCA) to the posterior segment of the eye. A screening based on TCA solubility was conducted on each excipient followed by preparation of various formulations using different ratios of the selected excipients. Vesicles of optimized SNEDDs had less than 100 nm size and spherical morphology. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay showed self-emulsified vesicles have relatively high safety on retinal pigment epithelium (RPE) cell line. Furthermore, efficient cellular uptake of coumarin 6-loaded SNEDDs in RPE using confocal laser scanning microscopy (CLSM) was confirmed. In addition, an in-vivo study using hematoxylin and eosin (H&E) staining revealed that 14 days of topical treatment of albino rabbit eyes with TCA-loaded SNEDDs was safe and no sign of tissue destruction and inflammation was detected in different parts of the eye sections including cornea, sclera, retina, and optic nerve. Also, the CLSM images from topically treated eyes with coumarin 6 (a hydrophobic, fluorescent drug model) loaded SNEDDs, showed that the optimized SNEDDs could properly penetrate toward the posterior segments of the eye especially the retina, posterior parts of the choroid, and sclera. Considering the outstanding results obtained by ocular tissue penetration and low toxicity, prepared SNEDDs, have the potential to be used as a topical administration for treating posterior segment disorders of the eye through an utterly non-invasive route and TCA-loaded SNEDDs could be an alternative for TCA intravitreal and intra conjunctival injections. [ABSTRACT FROM AUTHOR]

Open globe trauma is the major cause for single eye blindness that stem from subsequent proliferative vitreoretinopathy (PVR). Though biomaterials and tissue engineering have significantly advanced drug delivery and management of human diseases, currently there is no effective drug formulation or device to pharmacologically mitigate PVR formation after open-globe eye trauma. This highlighted the challenge we are facing to bring the technology from bench to bedside. The current study reported an engineered episcleral drug film using biodegradable material, Poly(L-lactide)- co -poly(ɛ -caprolactone), and triamcinolone acetonide (TA) as a model drug. The film can be conveniently sized into any shape to fit the configuration of the eye globe trauma and easily installed onto the ruptured sclera during primary trauma repair surgery. The film allows therapeutic TA to slow release for at least 6 months without toxicity and demonstrated a significant benefit to reduce the odds of developing severe PVR by 5.7 times when compared with a no-drug film control on a rabbit trauma PVR model. Our results suggested this micro episcleral drug film as promising drug delivery carrier for the targeted treatment of various unwanted retinal proliferation diseases. [Display omitted] • P(LLA-CL) film provides 4-month zero-order release of triamcinolone acetonide (TA) • The film can be tailored to any configuration to cover eye globe trauma at sclera • Duration of drug release may be customized by altering thickness of the film • The film self-degrades from sclera surface over time without adverse effect • The episcleral TA-film mitigates open-globe trauma induced PVR formation. [ABSTRACT FROM AUTHOR]

There are emerging reports of the effectiveness of in-office awake vocal-fold corticosteroid injection in the treatment of exudative vocal-fold lesions. The aim of this study was to review this therapy and specify indications, practical modalities and outcomes. Systematic review of the literature without meta-analysis. A systematic review by PubMed search for the period January 2000 to December 2018 was carried out. Nine articles were included, for a total of 502 lesions: nodules (46.4%), polyps (31.7%), and Reinke's edema (21.9%). Submucosal injection of low-dose triamcinolone acetonide (0.1 to 0.3 mL) was transoral, transcutaneous or transnasal via flexible endoscope with operating channel. Lesion volume was significantly reduced in more than 90% of cases, with significant vocal improvement in all studies. Relapse rates ranged between 4% and 31%, with time to relapse of 1 to 40 months. First-line treatment of exudative glottic lesions by submucosal corticosteroid injection provides at least transient significant reduction in lesion volume and vocal improvement. It is consensually reserved to moderate-sized mainly exudative lesions without fibrosis. In-office injection provides an immediate therapeutic response in case of vocal impairment, enabling surgery under general anesthesia to be postponed. [ABSTRACT FROM AUTHOR]

Lichen planus is a benign inflammatory disorder of unknown etiology that may affect the skin, mucosae, scalp, and nails. When the nails are affected, it may lead to permanent destruction with severe functional and psychosocial consequences. Therefore, prompt diagnosis and early treatment are essential, even in mild cases. There are currently no guidelines for the management of nail lichen planus and the published literature on treatment is limited. The aim of this review is to provide practical management recommendations for the classical form of nail lichen planus, especially when restricted to the nails. Topical treatment has poor short-term efficacy and may cause long-term side effects. Instead, intralesional and intramuscular triamcinolone acetonide should be considered first-line therapies. Oral retinoids are second-line choices, and immunosuppressive agents may also be considered. [ABSTRACT FROM AUTHOR]

To evaluate whether the therapeutic effect of ultrasound-guided injections with 10 mg or 40 mg triamcinolone acetonide (TA) was dose-dependent in patients with idiopathic mild to moderate carpal tunnel syndrome (CTS). Prospective, double-blind, randomized controlled study with 12 weeks of follow-up. Rehabilitation outpatient clinic of a single medical center. Patients with CTS (N=56). Participants were randomly assigned to 2 treatment groups for injection: (A) 40 mg TA+2% lidocaine hydrochloride or (B) 10 mg TA+2% lidocaine hydrochloride. Participants were evaluated using visual analog scale (VAS) and Boston Carpal Tunnel Questionnaire (BCTQ, including Symptom Severity Scale [SSS] and Functional Status Scale [FSS]) at baseline and 6 and 12 weeks after injection). Nerve conduction studies, including parameters of distal motor latency, amplitude of compound motor action potential, amplitude of sensory nerve action potential and sensory nerve conduction velocity of median nerve, and the patient's subjective impression of improvement, were recorded before injection and 6 and 12 weeks after injection. No significant differences were observed in baseline demographic characteristics and clinical evaluations. The parameters in group A and B at baseline, 6 weeks, and 12 weeks were (1) SSS: 2.17±0.14, 1.19±0.04, and 1.34±0.09 and 1.87±0.11, 1.21±0.07, and 1.26±0.04; (2) FSS: 1.63±0.07, 1.27±0.06, and 1.33±0.08 and 1.50±0.10, 1.18±0.05, and 1.26±0.05; (3) VAS: 6.4±0.3, 2.2±0.3, and 3.0±0.1 and 6.7±0.3, 2.0±0.3, and 3.1±0.3, respectively, and significantly decreased after 6 and 12 weeks in both treatment groups (P <.05). All parameters of nerve conduction studies improved in both groups after 12 weeks (P <.05). VAS, BCTQ, and nerve conduction studies did not show significant intergroup differences after 6 and 12 weeks. In patients with idiopathic mild to moderate CTS, ultrasound-guided injection with 10 and 40 mg TA yield similar improvements in BCTQ, VAS, and nerve conduction studies at the 12-week follow-up. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a synovial inflammatory condition characterized by cartilage destruction and osteophyte formation. Macrophages play a central role in OA pathogenesis by producing proinflammatory cytokines. Intra-articular corticosteroid administration can relieve refractory pain and inflamed effusion of knee joints. However, limitations, such as rapid clearance from the joint space, potential damage to articular cartilage, and accelerated joint degeneration, may hamper the clinical application of corticosteroids. In this study, we reported the design and preparation of dextran sulfate-triamcinolone acetonide conjugate (DS-TA) nanoparticles (NPs) for treating OA by specifically targeting scavenger receptor class A (SR-A) on activated macrophages. We verified the excellent targeting specificity of DS-TA NPs to SR-A by flow cytometry and confocal laser scanning microscopy. DS-TA NPs were found to effectively reduce the viability of activated macrophages (RAW 264.7 cells) and the expression of proinflammatory cytokines. Intra-articular injection of DS-TA NPs effectively alleviated the structural damages to the joint cartilage, as confirmed in histopathological analysis. Additionally, DS-TA NPs decreased the expression of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, in the cartilage tissue. Thus, DS-TA NPs are a potential therapeutic nanomedicine for the targeted treatment of OA. • Dextran sulfate-triamcinolone acetonide conjugate (DS-TA) is synthesized and self-assembled into micellar nanoparticles. • The obtained DS-TA NPs specifically targeted scavenger receptor class A (SR-A) on the surface of activated macrophages • DS-TA NPs inhibited the proliferation of activated macrophages and decreased the expression of proinflammatory cytokines. • DS-TA NPs effectively alleviated the structural damage of joint cartilage and the loss of subchondral bone. • DS-TA NPs are promising for targeted treatment of OA. [ABSTRACT FROM AUTHOR]

Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME). Phase 3 masked, randomized trial. One hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye. Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week 12. The primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfield thickness (CST) at week 24. In the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P < 0.001), meeting the primary end point. Mean reductions in CST from baseline were 153 μm versus 18 μm (P < 0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of the CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%, respectively). Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder. [ABSTRACT FROM AUTHOR]

Drug delivery to the posterior eye is limited by epithelial and mucosal barriers limiting the topical administration of drugs leading to invasive modes of repeated long-term painful administration of drugs. Several constructs of liposomes have been prepared to counter this challenge yet are often limited by size and surface charge resulting in poor encapsulation efficiency, low retention time, and poor permeability. In the present study, chitosan coated liposomes (CCL) were prepared to address these challenges. Conventional liposomes encapsulating Triamcinolone Acetonide (TA) were compared with their chitosan coated counterpart for drug loading and release studies. CCL showed a higher encapsulation efficiency (74%), and a highly positive surface charge (+41.1Mv), increased retention time and sustained release. Choroidal neovascularization (CNV) rat models were generated to assess the efficiency of CCLs as nanocarriers in drug delivery. Significant amount of TA was found to be present and retaining in the eye after fifteen days of treatment with CCL, as shown by HPLC analysis. The results showed successful penetration of the construct via corneal mucosal barrier and its accumulation in vitreous body. The analysis shows that this chitosan based liposomal construct can be employed as a potential topical delivery system for treating posterior segment diseases. [ABSTRACT FROM AUTHOR]

Oral mucosal drug delivery systems have been developed to expedite the regeneration of oral mucosa, there are still many challenges related to residence time for drugs because the ceaseless changes of saliva, mouth movement, and involuntary swallowing prevent robust adhesion of drugs and/or drug-loaded biomaterials. Thus, it is highly desirable to develop the delivery platforms exhibiting robust, stable adhesion within oral cavities. Herein, we have developed an adhesive polysaccharide oral patch called 'Chitoral' that utilizes chemical principles shown in wet-resistant mussel adhesion. Chitoral plays an important role as an adhesive layer in wet environments. We unexpectedly found that Chitoral instantly dissolves upon contact with saliva and a labial mucous layer, and then the dissolved Chitoral compounds forms an insoluble adhesion layer with mucins at Chitoral/mucous interface nearly immediate actions. Later, Chitoral gradually converts into adhesive hydrogels by the cooperative actions of covalent crosslinking and physical entanglement. The instant, robust muco-adhesion properties of Chitoral provides long-lasting therapeutic effects of drugs resulting enhanced healing of oral ulcer. Thus, mussel-inspired, mucous-resistant adhesive platforms, Chitoral, can be a platform for oral mucosal drug delivery systems. Unlabelled Image • Mussel-inspired, chitosan-catechol adhesive patches (Chitoral) for mucosal drug delivery. • Chitoral formed hydrogel-like adhesive layers upon contact with saliva. • Cooperative actions of covalent bonds and physical entanglement at mucosal interfaces. • Ability to promote healings of oral ulcer by a release of triamcinolone acetonide. [ABSTRACT FROM AUTHOR]

Triamcinolone Acetonide (TA , Steroid Medication) solubility in supercritical carbon dioxide (ScCO 2) was determined for the first time at 308, 318, 328, and 338 K and pressures of 120–270 bar. The results showed that mole fractions of TA dissolved in ScCO 2 ranged from 6.90 × 10−6 to 2.13 × 10−4, and the solubility ranged from 0.052 to 1.650 g/L. Four different types of models were examined; (1) seven known density-based models, with 3–6 adjustable parameters, namely Sung-Shim, Chrastil, Kumar–J and Bian et al., MST, Bartle, and Sodeifian; (2) Equation of state (EoS) based model, specifically Peng-Robinson (PR) EoS, coupled with two conventional types of van der Waals mixing rules; (3) a Solid-Liquid Equilibrium (SLE) based model, developed by Soedifian et al. ,; (4) several machine learning-based models, namely Ridge Regression, Huber Regression, Random Forest, and Gaussian Process. Based on the results, all applied models accurately described TA solubility in ScCO 2 , although Sodeifian et al. model led to superior results based on AARD% and Kumar–Johnston model based on Bayesian Information Criterion (BIC). Finally, thermodynamic enthalpies of TA were estimated for the first time. [Display omitted] • The solubility of Triamcinolone Acetonide (TA) in ScCO 2 was measured for the first time. • Mole fractions ranged from 6.90 × 10−6 to 2.13 × 10−4, for solubilities of 0.052–1.650 g/L. • The solubility data of TA were correlated by different models (Sodeifian model is the best). • Different machine learning algorithms were examined. • The different enthalpies of Triamcinolone Acetonide (TA) drug were determined. [ABSTRACT FROM AUTHOR]

Applied materials from bio-wastes are becoming the center of attention for researchers due to convincing concerns for their effectiveness, bio-sustainability, affordability, and environmental friendliness. In this research, different forms of carbon particles (CP) were produced from walnut shells to check their response against acne. Surface chemistry of CPs was modified in two steps: first, by thermal or oxidative-thermal treatment, and second, by biochemical treatment with the drugs triamcinolone acetonide (TA) or hydrocortisone sodium succinate (HSS) at pH 4 and 7. Prepared CPs have been analyzed for their surface chemistry, morphology and bioactivity. With the exception of GTOT, surface modifications have decreased oil absorption capacity and drug release pattern while increasing dispersion, pH and base contents. The GTOT and PTOT-N1 samples exhibited highest oil absorption capacities of 0.137 g/0.05 g and 0.130 g/0.05 g, respectively. Additionally, thermal and thermo-chemical modifications have slightly decreased in-vitro anti-inflammatory activity but substantially decreased cytotoxicity (almost 5–6 folds in comparison to unmodified particles). Anti-inflammatory response has been checked against P. acnes. Among various prepared samples, it was observed that Bio-PUT-4 and Bio-PTOT-7 exhibited the most significant levels of anti-inflammatory activity, at 94.19 % and 93.54 % respectively. Thermally modified samples, additionally, have shown magnetic behavior. [Display omitted] • Bio-waste (Walnut shell) as source of carbon particles. • Thermal, Thermo-chemical, Biochemical surface modification. • Preparation of eco-friendly skincare product. • Promoting environmental sustainability through the recycling of bio-waste materials. [ABSTRACT FROM AUTHOR]

• DBD treatment is effective for GC removal in various water matrices. • Rate constant and energy yield were measured at various factors. • Roles of HO and e aq − generated during DBD treatment were verified. • O 3 , H 2 O 2 , and UV generated during DBD treatment also contribute to GC removal. • Degradation pathway and mechanism of FA, TA, and CP were proposed. Performance and mechanism of non-thermal plasma (NTP) technology in removing glucocorticoids (GCs) was investigated using a dielectric barrier discharge (DBD) reactor with fluocinolone acetonide (FA), triamcinolone acetonide (TA) and clobetasol propionate (CP) as representative compounds. Effects of discharge power, plasma-working gases, initial pH, coexistence of ions, and various water matrices (ultrapure water, lake water, drinking water, wastewater effluent) on GC removal and energy yield were evaluated. The results confirm that DBD treatment could efficiently remove FA, TA, and CP, achieving efficiency of 72% (k = 0.0126 min−1), 71% (k = 0.0096 min−1), and 74% (k = 0.0116 min−1), respectively in air-DBD system at 45.2 W, with the process following the first order kinetics and energy yield of 6 mg kW−1h−1. The removal efficiency decreased when adding radical scavengers, indicating that hydroxyl radicals played an important role in GC degradation, while other active species (such as solvated electrons (e aq −), ozone (O 3), hydrogen peroxide (H 2 O 2) and ultraviolet photolysis (UV)) also contribute to GC degradation. The intermediates generated during the process were analyzed using quadrupole time-of-flight mass spectrometry (QTOF-MS). A total of 23 transformation products of FA, TA and CP were identified, and it was noted that substitution of halogen atoms with OH, oxidation of hydroxyl group to keto acid, decarboxylation of the keto acid, addition of OH, intramolecular cyclization, and hydrolysis of esters occurred during GC degradation by DBD treatment. [ABSTRACT FROM AUTHOR]

Nowadays the use of sustainable polymers as poly-lactic acid (PLA) and poly-δ-decalactone (PDL) in drug delivery is advantageous compared to polymers derived from fossil fuels. The present work aimed to produce microparticles (MPs) derived from novel sustainable polymers, loaded with triamcinolone acetonide (TA) for treatment of rheumatoid arthritis via intra-articular (IA) delivery. PDL was synthesized from green δ-decalactone monomers and co -polymerized with methoxy-polyethylene glycol (mPEG) forming PEG-PDL with different molecular weights. The Hansen's solubility parameters were applied to select the most compatible polymer with the drug. An o/w emulsion/solvent evaporation technique was used for MPs fabrication, using 3 [ 3 ] full factorial design. Selection of the optimized MPs was performed using Expert Design® software's desirability function. The optimized formulations were characterized using scanning electron microscope, powder X-ray diffraction, differential scanning calorimetry, infrared spectroscopy and in vitro release studies. The inhibition percents of inflammation and histopathological studies were assessed in complete Freund's adjuvant-induced rats' knee joints evaluating the effect of IA injections of selected MPs compared to the free drug suspension. Solubility studies revealed high compatibility and miscibility between TA and PEG-PDL 1700 , which was blended with PLA for convenient MPs formation. The in vitro characterization studies confirmed the formation of drug-copolymer co-crystals. The in vivo studies ensured the superiority of the newly designed composite MPs in inflammation suppression, compared to the free drug suspension and PLA MPs as well. The present study proved the advantage of using sustainable polymers in a novel combination for effective drug delivery and suggesting its usefulness in designing versatile platforms for therapeutic applications. Unlabelled Image • Six different PEG-PDL copolymers were synthesized using ring opening polymerization. • Hansen's solubility parameters confirmed high drug–copolymer compatibility. • TA-loaded PLA/PEG-PDL MPs were developed and optimized via a statistical design. • In vitro characterization studies endorsed the formation of TA-copolymer co-crystal. • The composite MPs showed a sustained anti-inflammatory action in rats' arthritic joints. [ABSTRACT FROM AUTHOR]

• Bis-imidazolium amphiphile forms supramolecular gels with anti-psoriatic drugs. • Drugs remain inside and outside the fibers, and can be released from both sites. • Speed of release from either site depends on drug physicochemical properties. • Gels promote drug permeation and retention within human skin. • Gels effectively prevent psoriasis signs in vivo , better than drugs in solution do. Supramolecular hydrogels were synthesized using a bis-imidazolium based amphiphile, and incorporating chemically diverse drugs, such as the cytostatics gemcitabine hydrochloride and methotrexate sodium salt, the immunosuppressive drug tacrolimus, as well as the corticoid drugs betamethasone 17-valerate and triamcinolone acetonide, and their potential as drug delivery agents in the dermal treatment of Psoriasis was evaluated. The rheological behavior of gels was studied, showing in all cases suitable viscoelastic properties for topical drug delivery. Scanning electron microscopy (SEM) shows that the drugs included have a great influence on the gel morphology at the microscopic level, as the incorporation of gemcitabine hydrochloride leads to slightly thicker fibers, the incorporation of tacrolimus induces flocculation and spherical precipitates, and the incorporation of methotrexate forms curled fibers. 1H NMR spectroscopy experiments show that these drugs not only remain dissolved at the interstitial space, but up to 72% of either gemcitabine or methotrexate, and up to 38% of tacrolimus, is retained within the gel fibers in gels formed with a 1:1 gelator:drug molar ratio. This unique fiber incorporation not only protects the drug from degradation, but also importantly induces a Two Phase Exponential drug release, where the first phase corresponds to the drug dissolved in the interstitial space, while the second phase corresponds to the drug exiting from the gel fibers, and where the speed in each phase is in accordance with the physicochemical properties of the drugs, opening perspectives for controlled delivery. Skin permeation ex vivo tests show how these gels successfully promote the drug permeation and retention inside the skin for reaching their therapeutic target, while in vivo experiments demonstrate that they decrease the hyperplasia and reduce the macroscopic tissue damage typically observed in psoriatic skin, significantly more than the drugs in solution. All these characteristics, beside the spontaneous and easy preparation (room temperature and soft stirring), make these gels a good alternative to other routes of administration for Psoriasis treatment, increasing the drug concentration at the target tissue, and minimizing side effects. [ABSTRACT FROM AUTHOR]

A hypertrophic scar (HS) is a cutaneous condition characterized by deposits of excessive amounts of collagen that produces a raised scar, causing physical, psychological, and cosmetic problems for the patient. The therapeutic efficacy of conventional transdermal drug delivery systems is often limited because the HS tissue is more compact than normal skin. At present, intralesional multi-injection of triamcinolone acetonide (TA) using a syringe is one of the most commonly used treatments for HS. However, the efficacy of this treatment is highly dependent on the skill of the medical professionals administering the injection. Even with co-administration of local anesthetics, traditional injection still causes pain to the patients, resulting in poor compliance. The purpose of this study was to provide an alternative treatment for HS by establishing a novel intradermal delivery system with a dissolving microneedle array (DMNA). To produce needles of higher mechanical strength for successful insertion into the compact and hard HS tissue, hydroxypropyl-β-cyclodextrin (HP-β-CD) was added into sodium hyaluronic acid (HA), the needle material. The hydrogen interaction between HP-β-CD and HA restricted the mobility of the molecular chains, and subsequently increased the elastic modulus of the complex materials. The HP-β-CD also contributed to improved loading of the hydrophobic drug molecules into the DMNA needle tips. To assess the delivery of TA to the HS site via DMNA, an HS model was established in the ventral skin of New Zealand rabbits' ears. It was found that the value of the scar elevation index was decreased to normal, together with the down regulation of mRNA expressions of Collagen I and transforming growth factor-β1 (TGF-β1) following the administration of DMNA containing TA (TA-DMNA). Western blotting results also revealed decreased protein expressions of both Collagen I and TGF-β1. Hence, TA-DMNA appears to be a promising alternative to multi-injection of TA injection, providing a convenient and low-pain therapeutic strategy for HS treatment. Unlabelled Image [ABSTRACT FROM AUTHOR]

• Fluticasone propionate and triamcinolone acetonide led to physiological effects. • Glucocorticoids altered expression of target genes encoding important pathways. • Glucocorticoid mixtures were additive. • Mixture activity supports the concentration addition concept. • Additive action of glucocorticoids may have adverse consequences. Many synthetic glucocorticoids from medical applications occur in the aquatic environment. Whether they pose a risk for fish health is poorly known. Here we investigate effects of glucocorticoids fluticasone propionate (FLU) and triamcinolone acetonide (TRI) as single steroids and as ternary mixtures with clobetasol propionate (CLO) in zebrafish embryos. Exposure to FLU and TRI in a range of concentrations between 0.099 and 120.08 μg/L led to concentration-related decrease in muscle contractions and increase in heart rate at 0.98 and 1.05 μg/L, respectively, and higher. Genes encoding for proteins related to glucose metabolism (g6pca , pepck1), immune system regulation (fkb p5 , irg1l, socs3 , gilz) and matrix metalloproteinases mmp-9 and mmp-13 showed expressional alterations, as well as genes encoding for the progestin receptor (pgr) and corticosteroid dehydrogenase (hsd11b2). FLU accelerated hatching and led to embryotoxicity (immobilization and edema). Ternary mixtures (FLU + TRI + CLO) induced the same physiological and toxicological effects at concentrations of individual glucocorticoids of 11.1–16.37 μg/L and higher. Heart rate was increased in the mixture at concentrations as low as 0.0885−0.11 μg/L of each steroid. Glucocorticoids in mixtures showed additive activity; the fold-changes of transcripts of 19 target genes were additive. Together, our data show that glucocorticoids act additively and their joint activity may be of concern for developing fish in contaminated environments. [ABSTRACT FROM AUTHOR]

After application to the skin surface, a topical formulation is submitted to changes in composition produced by evaporation of volatile components, penetration of components into the skin and extraction of skin components ("vehicle metamorphosis"). The aim of this work was to study the effect of vehicle metamorphosis on skin delivery from microemulsions containing triamcinolone acetonide. The microemulsions were prepared and characterized for water evaporation kinetics, in vitro release and skin permeation and retention. Skin retention experiments were performed on full thickness pig ear skin, in both occluded infinite and un-occluded finite dose conditions. For comparison purposes, two creams, the commercial Ledercort® and a vanishing cream, were tested. With triamcinolone acetonide water evaporation does not modify skin retention, probably for the lipophilic nature of the drug. However, if water is eliminated from the microemulsions, the performance is reduced, probably because drug partitioning from vehicle to stratum corneum is disfavored. If a water-soluble drug (methyl prednisolone sodium succinate) is used, infinite dose application in occlusive conditions increases in a significant way the amount of drug retained in the skin. The involved mechanisms are probably stratum corneum swelling and increase of stratum corneum/viable epidermis partitioning. [ABSTRACT FROM AUTHOR]

Pharmaceutical emulsions contain multiple components, such as micellar, aqueous, and oil phases, leading to complex drug transfer and equilibrium phenomena. These complex components present challenges for the bioequivalence assessment of the drug products. The objective of the study was to develop a method that can probe the underlying mechanism and process of drug distribution. The concept of drug partitioning into biphasic systems was used to simplify the complex transfer phenomenon. A kinetic method was developed taking into account the biphasic diffusion. Using this approach, both the rate (kinetics) and the extent (equilibrium) of distribution can be determined. For method development purpose, 3 model compounds (triamcinolone acetonide, difluprednate, and cyclosporine), with expected partition coefficient values ranging from 2 to 6, were tested using the kinetic method and the traditional shake-flask method. The values obtained by the 2 methods for all compounds correlated well (r2 = 0.825). Various organic and aqueous solvents which are commonly encountered in formulations were also tested to determine the impact of phase composition on drug distribution. The kinetic method was found to offer more flexibility in terms of solvent composition and can lead to better understanding for drug distribution and potential drug release in complex biphasic systems. [ABSTRACT FROM AUTHOR]

Abstract Triamcinolone acetonide (TCA) abuse in cosmetics is a common phenomenon. A rapid lateral flow immunochromatographic assay (ICA) was developed for the quantitative detection of TCA using a probe based on upconversion luminescence nanoparticles. Lanthanide-doped upconversion nanoparticles (UCNPs) were synthesized in a system comprising water and ethylene glycol, and a silicon dioxide layer was covered at the carboxyl site. A binding site protection strategy was used to decrease the background signal of UCNPs-ICA. Using dexamethasone derivative as a coating antigen, the optimal UCNPs–ICA exhibits good dynamic linear detection for TCA in the range 1.0–100 ng mL−1 with a median inhibitory concentration of 9.8 ng mL−1. The detection limits for TCA in a cosmetic sample are 20 μg kg−1. The pretreatment of samples only needs dilution with water, suggesting the assay can quantitate TCA on-site using a portable upconversion luminescence reader with a cumulative analysis time of only 10 min. Graphical abstract Unlabelled Image Highlights • SiO 2 covered sensitive UCNPs were explored as probes in the competitive strip assay. • New method allowed easy and controlled preparation of antibody-UCNPs conjugates. • TCA was quantitatively detected by the novel fluorescent reader-based strip test. [ABSTRACT FROM AUTHOR]

Background Context: Local corticosteroids have been used to relieve symptoms of chronic low back pain, although treatment effects have been shown to wear off relatively fast. Prolonging corticosteroid presence by controlled release from biomaterials may allow for longer pain relief while circumventing adverse effects such as high bolus dosages.Purpose: The purpose of this study was to evaluate the safety and efficacy of intradiscal controlled release of triamcinolone acetonide (TAA) by poly(esteramide) microspheres in a canine degenerated intervertebral disc (IVD) model.Study Design: In a preclinical experimental large animal model, the effect of prolonged glucocorticoid exposure on disc degeneration was evaluated.Methods: Degeneration was accelerated by nucleotomy of lumbar IVDs of Beagle dogs. After 4 weeks, microspheres loaded with 8.4 µg TAA, and 0.84mg TAA were administered to the degenerated IVDs by intradiscal injection (n=6 per group). Empty microspheres (n=6) and all adjacent non-nucleotomized noninjected IVDs were included as controls (n=24). Immediately prior to TAA administration and after 12 weeks, magnetic resonance imaging was performed. Degenerative changes were evaluated by disc height index, Pfirrmann grading, T1ρ and T2 mapping values, postmortem CT scans, macroscopic and microscopic grading, and biochemical/immunohistochemical analysis of inflammation and extracellular matrix content. In addition, nerve growth factor (NGF) protein expression, a biomarker for pain, was scored in nucleus pulposus (NP) tissues. The study was funded by a research grant from Health Holland (1.3million euros = 1.5million US dollars).Results: Macroscopic evaluation and CT images postmortem were consistent with mild disc degeneration. Other abnormalities were not observed. Nucleotomy-induced degeneration and inflammation was mild, reflected by moderate Pfirrmann grades and PGE2 levels. Regardless of TAA dosage, local sustained delivery did not affect disc height index nor Pfirrmann grading, T1ρ and T2 mapping values, PGE2 tissue levels, collagen, GAG, and DNA content. However, the low dosage of TAA microspheres significantly reduced NGF immunopositivity in degenerated NP tissue.Conclusions: This is the first in vivo application in a preclinical large animal model of a controlled release formulation of corticosteroids in mild IVD degeneration. Sustained release of TAA locally in the IVD appeared safe and reduced NGF expression, suggesting its potential applicability for pain relief, although beneficial effects were absent on tissue degeneration.Clinical Significance: The present platform seems to be promising in extending the local controlled delivery of TAA with the potency to provide long-standing analgesia in the subset of LBP patients suffering from discogenic pain. [ABSTRACT FROM AUTHOR]

Idiopathic orbital inflammation developed in the right orbit of a woman in her mid-thirties, causing tearing, photophobia, diplopia, altered depth perception, proptosis, and pain on eye movements. Computed tomography disclosed a mass involving the intraconal and extraconal nasal right orbit, extending to the orbital apex with anterior displacement of the globe, effacement of the medial rectus muscle, portions of the fat plane, and the superior oblique muscle, and bone destruction with extension of the mass through the orbital floor into the superior maxillary sinus and through the lamina papyracea into the ethmoid sinus. Orbital biopsy disclosed dense fibrous connective tissue with numerous lymphocytes and macrophages. Immunohistochemical stains supported a diagnosis of idiopathic inflammatory pseudotumor involving the orbit and sinus mucosa. Treatment with a prednisone taper and a retrobulbar injection of triamcinolone acetonide have relieved her symptoms and diminished her proptosis. This patient highlights the rare potential of idiopathic orbital inflammation to erode though bone into adjacent cranial structures. [ABSTRACT FROM AUTHOR]

Highlights • ZnO-decorated SnO 2 spheres were synthesized via a facile solvothermal method. • ZnO decoration led to greatly enhanced NO 2 gas sensing performance. • A high response of 258 to 100 ppm NO 2 was achieved for ZnO/SnO 2 composite. Abstract In this work, ZnO was decorated onto SnO 2 microspheres via a facile solvothermal method, and the gas sensing characteristics of the ZnO/SnO 2 composites was systematically studied. Results showed that the ZnO/SnO 2 composites was highly responsive to NO 2 , with much lower response to interfering gases such as ethanol and acetone. At the optimum temperature (200 °C), the response of the ZnO/SnO 2 composite to 100 ppm NO 2 was about 3 times higher than that of pristine SnO 2 microspheres. Furthermore, ZnO decoration on SnO 2 microspheres led to significant reduction in the response time. The improvement of gas-sensing performance may be ascribed to the formation of more surface adsorption sites on the ZnO/SnO 2 composite. [ABSTRACT FROM AUTHOR]

Purpose: To report the one-year outcomes of diabetic macular edema (DME) treated with ranibizumab under a real-life setting in Taiwan, and to identify the prognostic factors.Methods: Between July 2013 and January 2015, 119 eyes receiving intravitreal ranibizumab for DME were retrospectively recruited. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) measured with optical coherence tomography were collected at baseline and at Month 3, 6, and 12. Linear regression was used to identify the predicting factors for changes in BCVA and CFT at Month 12.Results: The average number of ranibizumab given within one year was 4.36 ± 1.87. The BCVA (logMAR) improved from 0.74 ± 0.30 at baseline to 0.64 ± 0.37 at Month 12 (p = 0.002). A better improvement in BCVA at Month 3 was significantly correlated with a better visual improvement at Month 12 (p < 0.001). The existence of subretinal fluid at baseline (p = 0.02) and a greater reduction in CFT at Month 3 (p < 0.001) were both correlated with a greater reduction in CFT at Month 12. Previous subtenon injection of triamcinolone acetonide was associated with fewer additional IVR after Month 3 (odds ratio = 0.35, 95% CI = 0.14-0.89).Conclusion: Compared with existing prospective studies, the one-year real-life data in Taiwan showed fewer ranibizumab injections for DME and a less prominent yet still significant visual improvement. Both visual and anatomical improvements at Month 3 were correlated with the level of improvements at Month 12. Previous subtenon steroid injection might reduce the need of additional ranibizumab injections. [ABSTRACT FROM AUTHOR]

[Display omitted] • Polymeric lipid hybrid nanoparticles (PLHNPs) of triamcinolone acetonide (TAA) were prepared for topical ocular administration. • The principles of design of experiments were used to optimize the TAA PLHNPs. • The optimized TAA-PLHNPs were evaluated on various physicochemical parameters. • The optimized TAA-PLHNPs were loaded in a dual responsive in situ gel. • TAA PLHNPs loaded in situ gel achieved significantly higher vitreous humor concentrations compared to aqueous suspension of TAA. Posterior uveitis (PU), which often has an autoimmune origin, can be treated effectively with synthetic glucocorticoid triamcinolone acetonide (TAA). Due to the limitations of topical TAA administration reaching the posterior segment of the eye, the drug is injected directly into the eye through an intravitreal injection. In this study, we prepared TAA loaded poly(lactic-co-glycolic acid) phosphatidylcholine hybrid nanoparticles (TAA-PLHNPs) using the principles of design of experiments (DoE) for topical ocular administration. The mean particle size (nm) and drug loading efficiency (LE%) for the optimized formulations were 163 ± 2.8 nm and 39 ± 1.9%, respectively. The TAA-PLHNPs were then loaded into the dual responsive in situ gel that we reported in our previous work. In vitro assessments were done to show that the formulations are safe for ocular administration. Finally, in vivo ocular pharmacokinetic studies were performed to compare pharmacokinetic parameters of TAA-PLHNPs and TAA-PLHNPs loaded in situ gel with each other and with the previously reported conventional formulation of TAA (aqueous suspension of TAA with 20% hydroxypropyl β-cyclodextrin (TAA-HP-β-CD-Susp)). TAA-PLHNPs loaded dual responsive in situ gel (TAA-PLHNP-ISG) achieved higher concentrations of TAA in the vitreous humor (C max of 946.53 ng/mL) and sustained (MRT 0–∞ of 16.26 h) the drug concentrations for longer period of time compared to aqueous suspension of TAA-PLHNPs (TAA-PLHNP-Susp) and TAA-HP-β-CD-Susp. [ABSTRACT FROM AUTHOR]

[Display omitted] The expression of inflammatory markers and vascular endothelial growth factor (VEGF) was found to be upregulated in various posterior ocular disorders, including diabetic retinopathy (DR). Effective delivery of therapeutic agents to the retina poses a significant challenge in ophthalmic drug delivery due to biological ocular barriers. Triamcinolone acetonide (TA) was selected as the model corticosteroid drug targeting cytokines and VEGF in DR. However, despite TA's low molecular weight and hydrophobicity, which enable it to bypass the conjunctival epithelial barrier, it doesn't efficiently exert its effect at the target site. Nanocarriers have emerged as a solution to enhance drug delivery to the retina and improve bioavailability. This study aimed to compare the effects of Triamcinolone-loaded cubic liquid crystalline nanoparticles (TA-cubic LCNPs) and TA-Suspension in an experimental DR model administered via the subconjunctival (SCJ) route. The results demonstrated that TA-cubic LCNPs enhanced TA periocular delivery efficacy by reducing inflammatory and VEGF markers through the advanced glycation end products (AGE)/protein kinase C pathway. They were identified as promising nano-carriers, exhibiting potential for targeted delivery to the retina. [ABSTRACT FROM AUTHOR]

Oral ulcers are common in the oral mucosa. Frequent occurrences of oral ulcers commonly afflict patients, seriously impacting their daily life. Treatments with good anti-inflammatory and antibacterial properties are important for promoting the healing of oral ulcers. In this study, a multifunctional, soluble hyaluronic acid (HA) microneedle (MN) patch was prepared to promote oral ulcer healing. The tip layer of the MN patch was loaded with triamcinolone acetonide (TA) and epidermal growth factor (EGF) to inhibit inflammation and promote angiogenesis. Zeolitic imidazolate framework-8 (ZIF-8) was loaded onto the base layer of the MN patch, which effectively released Zn2+ to mediate antibacterial effects. In addition, HA exerts a protective effect on the mucous membrane. Owing to these properties, the multifunctional MN patches were found to have good anti-inflammatory, antibacterial, and tissue-healing abilities, indicating that the multifunctional MN patch design successfully promoted the healing of oral ulcers. [ABSTRACT FROM AUTHOR]

Triamcinolone acetonide (TAA), a long-acting synthetic glucocorticoid, is commonly used for the management of posterior uveitis (PU) because of its anti-inflammatory and immunosuppressive characteristics. The commercially available formulation is in the suspension form advised for intravitreal injection, which has a number of serious problems. In the present research work, we prepared TAA nanocrystals (TAA-NCs) using the principles of design of experiments (DoE). The optimized TAA-NCs had a particle size of 243.0 ± 6.5 nm and a yield (%) of 89.4 ± 4.3%. The optimized TAA-NCs were suspended in a dual-responsive in situ gelling system, which has been previously reported by our team. The TAA-NCs loaded in situ gel (TAA-NC-ISG) formulations were evaluated for rheology, stability, in vitro and in vivo characteristics. The ocular pharmacokinetic investigations revealed that TAA-NCs loaded in situ gel achieved higher concentrations (C max of TAA-NC-ISG = 854.9 ng/mL) of the drug in vitreous humor and sustained (MRT 0–∞ of TAA-NC-ISG = 11.2 h) the drug concentrations for longer duration compared to aqueous suspension of TAA-NCs (TAA-NC-Susp) and aqueous suspension of TAA with 20% hydroxypropyl β-cyclodextrin(TAA-HP-β-CD-Susp) reported in our previous work. This higher exposure of TAA by TAA-NC-ISG is due to the combined effect of the nanometric size of the TAA nanocrystals and the in situ gelling properties of the formulation. • Triamcinolone acetonide (TAA) nanocrystals were prepared for topical ocular administration. • Hybrid design of experiments (DoE) approach was employed to optimize the TAA nanocrystals. • Physicochemical characterization of the optimized nanocrystal was performed. • The optimized nanocrystals were loaded in a dual responsive in situ gelling system. • The TAA nanocrystals loaded in situ gel showed significantly higher vitreous humor concentrations compared to aqueous suspension of TAA with 20% hydroxypropyl β-cylcodextrin. [ABSTRACT FROM AUTHOR]

[Display omitted] • Triamcinolone acetonide-loaded glycerospanlastics were successfully fabricated. • Glycerospanlastics showed a high drug entrapment and tympanic membrane permeation. • Ototopical glycerospanlastics displayed proficient otitis media treatment. • Safety and tolerability of ototopical glycerospanlastics were evidenced. The purpose of this research was to design innovative nanovesicles for ototopical conveyance of triamcinolone acetonide (TA) for otitis media (OM) treatment via incorporating glycerol into nanospanlastics to be termed "Glycerospanlastics". The glycerospanlastics were formulated employing ethanol injection procedure, and central composite design (CCD) was harnessed for optimization of the vesicles. Various attributes of the nanovesicles, viz. particle size distribution, surface charge, TA entrapment efficiency, morphology as well as ex-vivo permeation across the tympanic membrane (TM) were characterized. In vivo implementation of the optimized glycerospanlastics loaded with TA was appraised in OM-induced rats via histopathological and biochemical measurements of the tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) levels in ear homogenates. The safety and tolerability of optimized TA glycerospanlastics was also investigated in non-OM induced animals. The results demonstrated that the optimized TA-glycerospanlastics were in a nanometer range (around 200 nm) with negative charges, high TA entrapment (>85%), good storage properties and better TM permeation relative to TA suspension. More importantly, TA-glycerospanlastics performed better than marketed drug suspension in OM treatment as manifested by restoration of histopathological alterations in TM and lowered values of IL-1β and TNF-α. Glycerospanlastics could be promising safe ototopical nanoplatforms for OM treatment and other middle ear disorders. [ABSTRACT FROM AUTHOR]

The fully dissolving polymer solution is homogeneously mixed with the TA powder, forming a drug-loaded polymer solution. Subsequently, the polymer solution loaded in the syringe is successfully expelled through the needle into the joint cavity. When it contacts body fluid, the water-miscible solvent (NMP) dissipates instantaneously, and water penetrates the system, leading to polymer precipitation at the injection site. That is a solvent exchange process, contributing to the drug being trapped in a porous structure. A long-acting ISFI is finally established, and the drug is released from this porous polymer implant in a fashion of diffusion, dissolution, and erosion. In this way, TA inhibits inflammatory responses in arthritis models for several months. TA: triamcinolone acetonide; PLGA: Poly (lactic-co-glycolic acid); NMP: N-methyl-2-pyrrolidone; BB: benzyl benzoate. [Display omitted] Arthritis is a syndrome characterized by inflammation in the joints. Triamcinolone acetonide (TA) was used as an anti-inflammatory agent in the treatment of this disease. However, there are limitations to its clinical application, including rapid clearance from the joint cavity, potential joint damage from multiple injections, and adverse joint events. To address these drawbacks, we developed a tunable in situ forming implant loaded with TA. This injectable polymer solution utilized poly (lactic-co-glycolic acid) (PLGA) as an extended-release material. When injected into the joints, the solution solidifies into implants through a solvent exchange in the aqueous environment. The implants demonstrated robust retention at the injection site and released TA over several weeks even months through diffusion and erosion. By adding different proportions of low water-miscible plasticizers, the release period of the drug could be precisely adjusted. The plasticizers-optimized implants exhibited a tough texture, enhancing the therapeutic efficiency and drug safety in vivo. In arthritic model studies, the tunable TA-loaded implants significantly reduced swelling, pain, and motor discoordination, and also showed suppression of arthritis progression to some extent. These findings suggested that TA-loaded ISFI holds promise for managing inflammatory disorders in individuals with arthritis. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract In this paper, we presented a simple yet versatile strategy to generate a high drug payload nanoparticles by the combination with small molecular assembly and polymeric assembly for topical suppression of ocular inflammation. Upon physical mixing of the succinated triamcinolone acetonide (TA-SA) supramolecular hydrogel with the poly (ethylene glycol)-poly (ɛ-caprolactone)-poly (ethylene glycol) (PECE) aqueous solution at 37 °C, TA-SA/PECE nanoparticles formed spontaneously and characterized thoroughly by transmission electron microscopy (TEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The formed TA-SA/PECE nanoparticles displayed a comparable in vitro anti-inflammatory efficacy to that of native triamcinolone acetonide (TA), through a significant downregulation of various proinflammatory cytokines levels (e.g., NO, TNF-α) in a lipopolysaccharide (LPS) actived RAW264.7 macrophage. Meanwhile, the enhanced transcorneal drug permeability of TA-SA/PECE nanoparticles over that of TA suspension was clearly observed in an isolated rabbit cornea. Intraocular biocompatibility test demonstrated that TA-SA/PECE nanoparticles presented good biocompatibility after topical instillation during entire study period. More importantly, the TA-SA/PECE nanoparticles displayed superior therapeutic efficacy over that of the TA suspension in the endotoxin-induced uveitis (EIU) rabbit model via decreasing neutrophil infiltration in anterior chamber. Overall, the proposed TA-SA/PECE nanoparticles might be a promising candidate for uveitis therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract This study investigated short duration transscleral iontophoretic delivery of four triamcinolone acetonide (TA) amino acid ester prodrugs (TA-AA) (alanine, Ala; arginine, Arg; isoleucine, Ile and lysine, Lys) using whole porcine eyes globes in vitro. Post-iontophoretic biodistribution of TA was quantified by UHPLC-MS/MS in the different ocular compartments (cornea, aqueous humor, sclera, ciliary body, choroid and retinal pigmented epithelium (RPE), neural retina and vitreous humor). Transscleral iontophoresis (3 mA/cm2 for 10 min) increased total drug delivery of the TA-AA prodrugs by 14-30-fold as compared to passive diffusion. The TA-AA prodrugs had distinct biodistribution profiles – the penetration depth achieved was dependent on their physicochemical properties (e.g. lipophilicity for TA-Ile) and susceptibility to hydrolysis (e.g. TA-Arg). Intraocular drug distribution was also influenced by prodrug binding to melanin (TA-Lys). Interestingly, under conditions of equivalent charge (6 mA/cm2 for 5 min vs. 1.5 mA/cm2 for 20 min, i.e. 1.44 C respectively) the longer duration (20 min) at lower current density resulted in ∼6 times more TA delivery into the vitreous humor. Overall, the study provided further evidence of the potential of transscleral iontophoresis for the non-invasive treatment of posterior segment inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: The ear is the common site for keloid formation especially in women after ear piercing. Surgery is the main stay of treatment in these lesions but there are large numbers of treatment failures in surgery alone.Objective: The objective of this study was to compare the efficacy of post-excision intralesional 5-fluorouracil/triamcinolone acetonide (5-FU/TAC) and post-excision radiotherapy in the treatment of ear keloids.Study Design: A randomized controlled trial.Setting: The study was conducted from May 2014 to January 2015 at Jinnah Burn and Reconstructive Surgery Centre, Allama Iqbal Medical College, Lahore.Subject& Methodology: After approval from the hospital ethical committee, 60 patients presented in the outpatient department fulfilling the inclusion criteria were selected and randomly assigned in two groups with the help of the random number table. Patients in group A had excision followed by intralesional 5-FU/TAC injections while patients of group B had excision followed by radiotherapy. Patients were assessed at 6 months after completion of treatment for efficacy (no recurrence within 6 months of treatment).Results: In our study total of 60 patients completed the study, with 30 patients in each group. 7 patients (23.34%) in Group-A and 9 patients (30%) in Group-B were males while 23 patients (76.67%) in Group-A and 21 patients (70%) in Group-B were females i.e. male to female ratio is 1:2.75. Mean age was 31.8+6.48years. The comparison of frequency of efficacy in both groups showed that 73.33% (n=22) in Group-A and 43.33% (n=13) in Group-B had efficacy, p value was calculated as 0.01, showing a significant statistical difference.Conclusion: Excision and intralesional 5-FU/TAC is an effective treatment for keloids on the ears. [ABSTRACT FROM AUTHOR]

There are numerous studies identifying the presence and toxicity of glucocorticoids (GCs) in water; however, limited studies reported effective GC removal technologies. This study researched the efficiency of calcium peroxide (CaO 2 ) in removing GC in wastewater treatment plants (WWTPs) with triamcinolone acetonide (TA) as the representative. Effects of CaO 2 dosage, initial pH, and water matrix were investigated. The functional reactive oxygen species (ROS) during TA removal was tested. Specifically, TA degradation intermediates by CaO 2 oxidation were identified for the first time. GC toxicity change during TA removal was deduced. The results indicated that CaO 2 treatment can be an effective method for TA removal and toxicity decrease. At the reaction time of 60 min, more than 78% of TA can be degraded with CaO 2 at 0.05–4 g L −1 . The TA removal efficiency increased with the increase of CaO 2 dosage. The optimal initial pH value is 6.8. HCO 3 − , Cl − , and NO 3 − had inhibitive effects on TA removal while SO 4 2− had no effect and PO 4 3− had positive effect. Humic acid (HA) had positive effects on TA removal because of its obvious adsorption effects. The HO and O 2 − released by CaO 2 are the functional ROS for TA removal, among which HO is the most important one. Besides the oxidation of HO and O 2 − , the adsorption effects of CaO 2 and Ca(OH) 2 and the hydrolysis at alkaline conditions may also contribute to TA removal. Six intermediates were revealed during TA degradation, indicating the decrease in GC activity. [ABSTRACT FROM AUTHOR]

Corticosteroids are widely used in topical formulations such as creams (aqueous) and ointments (non-aqueous). The generally used corticosteroids show large molecular resemblance, where especially the 20-keto-21-hydroxyl group bound to the 17 carbon is important for their chemical stability. Oxidation in both aqueous and non-aqueous environment occurs for triamcinolone acetonide (TCA), hydrocortisone (HC) and desoximethasone (DS). Besides the 20-keto-21-hydroxyl group, TCA, HC and DS have different other moieties attached to the same C17. These moieties are shown to influence not only the type of degradation product formed but also the degradation kinetics. Seven degradation products are found in total and a degradation mechanism is proposed. Furthermore the transesterfication of betamethasone-17-valerate to betamethasone-21-valerate is shown to occur both in aqueous and non-aqueous environment. Finally, a comprehensive scheme of degradation pathways is presented that is applicable for both aqueous and non-aqueous formulations. [ABSTRACT FROM AUTHOR]