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This study presents the synthesis and optimization of Methylene polyethyl glycol −Polystyrene (mPEG-PS) Diblock (DIP) copolymer-based solid lipid nanoparticles (SLNs) using ultrasonication for advanced drug delivery systems targeting the human immunodeficiency virus (HIV-1). The mPEG-PS block copolymer was synthesized by ring opening polymerization mechanism under nitrogen atmosphere for 24hrs and characterized using Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy and NMR, confirming the formation of DIP polymers. Optimization of SLNs formulation was achieved through a systematic approach, utilizing response surface methodology, optimal conditions for SLNs synthesis were determined, resulting in nanoparticles with a particle size of 198 nm and an entrapment efficiency of 67.42 %. Cell viability assays, quantitative PCR for viral DNA analysis, caspase-3 enzyme assays, and quantitative uptake studies using High Performance Liquid Chromatography (HPLC) provided quantitative insights into the efficacy and biocompatibility of the synthesized nanoparticles. The experimental data demonstrate that nanoparticle treatments significantly influence cellular responses, providing valuable insights into their therapeutic potential and underlying mechanisms. By employing precise experimental methods alongside rigorous analytical techniques, this study enhances our understanding of nanoparticle-based drug delivery systems, particularly in the context of HIV treatment. These findings pave the way for optimizing therapeutic strategies to improve patient outcomes.

A binary blend of rosuvastatin (ROS) and teneligliptin (TEN) used for the management of cardiovascular complications require a simple, analytical process for the quality assurance of this formulation. UV absorption spectra of ROS and TEN showed overlapping spectra. Hence, the overlapped spectra of ROS and TEN were separated by ratio difference, ratio first derivative; constant extraction coupled with exponentiation with division spectrum, and induced dual-wavelength methods. The proposed methods were authenticated by following the international council for harmonization criteria. A good linear relationship was demonstrated by all four methods, in 2–15 and 2–30 µg/mL for ROS and TEN, respectively. The high percentage retrieval of 98.96–100.22 and 98.72–99.73% for ROS and TEN, respectively, with small relative error, assured the correctness of the techniques. The validated techniques were employed for concurrent evaluation of ROS and TEN from binary formulation and laboratory-prepared mixture. The standard addition process verified the reliability of the projected procedures. The developed methods showed same accuracy and precision when compared to the HPLC methods along with safer solvent. Finally, the environmental sustainability of the presented UV spectroscopic procedures was found to be better than the reported HPLC method. Hence, eco-friendly, simple, and accurate mathematically processed UV spectroscopic procedures can be employed for simultaneous quantification of ROS and TEN for routine quality control study.

Ovarian cancer is a malignant tumor that primarily forms in the ovaries. It often goes undetected until it has spread to the pelvis and abdomen, making it more challenging to treat and often fatal. Historically, natural products and their structural analogues have played a pivotal role in pharmacotherapy, especially for cancer. Numerous studies have demonstrated the therapeutic potential of Linum usitatissimum against ovarian cancer, but the specific molecular mechanisms remain elusive. This study combines data mining, network pharmacology, and molecular docking analysis to pioneer an innovative approach for ovarian cancer treatment by identifying potent phytochemicals. Findings of current study revealed that Apigenin, Vitamin E, Palmitic acid, Riboflavin, Isolariciresinol, 5-Dehydro-avenasterol, Cholesterol, Pantothenic acid, Nicotinic acid, Campesterol, Beta-Sitosterol, Stigmasterol, Daucosterol, and Vitexin suppress tumor growth by influencing AKT1, JUN, EGFR, and VEGFA. Kaplan–Meier survival analysis spotlighted AKT1, JUN, EGFR, and VEGFA as potential diagnostic and prognostic biomarkers for ovarian cancer. However, it is imperative to conduct in vivo and in vitro examinations to ascertain the pharmacokinetics and biosafety profiles, bolstering the candidacy of L. usitatissimum in ovarian cancer therapeutics.

Diabetes mellitus is one of the most concerning conditions, and its chronic consequences are almost always accompanied by infection, oxidative stress, and inflammation. Reducing excessive reactive oxygen species and the wound’s inflammatory response is a necessary treatment during the acute inflammatory phase of diabetic wound healing. Malva sylvestris extract (MS) containing nanofibers containing neomycin sulfate (NS) were synthesized for this investigation, and their impact on the healing process of diabetic wounds was assessed. Using Design Expert, the electrospinning process for the fabrication of NS nanofibers (NS-NF) was adjusted for applied voltage (X1), the distance between the needle’s tip and the collector (X2), and the feed rate (X3) for attaining desired entrapment efficacy [EE] and average nanofiber diameter (ND). The optimal formulation can be prepared with 19.11 kV of voltage, 20 cm of distance, and a flow rate of 0.502 mL/h utilizing the desirability approach. All the selected parameters and responses have their impact on drug delivery from nanofibers. In addition, M. sylvestris extracts have been added into the optimal formulation [MS-NS-NF] and assessed for their surface morphology, tensile strength, water absorption potential, and in vitro drug release studies. The NS and MS delivery from MS-NS-NF has been extended for more than 60 h. M. sylvestris-loaded nanofibers demonstrated superior antibacterial activity compared to plain NS nanofibers. The scaffolds featured a broad aspect and a highly linked porous fibrous network structure. Histomorphometry study and the in vitro scratch assay demonstrate the formulation’s efficacy in treating diabetic wound healing. The cells treated with MS-NS-NF in vivo demonstrated that wound dressings successfully reduced both acute and chronic inflammations. To improve the healing of diabetic wounds, MS-NS-NF may be regarded as an appropriate candidate for wound dressing.

Breast cancer is a silent killer disorder among women and a serious economic burden in healthcare management. Every 19 s, a woman is diagnosed with breast cancer, and every 74 s, a woman worldwide passes away from the disease. Despite the increase in progressive research, advanced treatment approaches, and preventive measures, breast cancer rates continue to increase. This study provides a combination of data mining, network pharmacology, and docking analysis that surely could revolutionize cancer treatment by exploiting prestigious phytochemicals. Crataegus monogyna is a small, rounded deciduous tree with glossy, deeply lobed leaves and flat sprays of cream flowers, followed by dark red berries in autumn. Various studies demonstrated that C. monogyna is therapeutically effective against breast cancer. However, the particular molecular mechanism is still unknown. This study is credited for locating bioactive substances, metabolic pathways, and target genes for breast cancer treatment. According to the current investigation, which examined compound–target genes–pathway networks, it was found that the bioactive compounds of C. monogyna may operate as a viable solution against breast cancer by altering the target genes implicated in the disease pathogenesis. The expression level of target genes was analyzed using GSE36295 microarray data. Docking analysis and molecular dynamic simulation studies further strengthened the current findings by validating the effective activity of the bioactive compounds against putative target genes. In summary, we propose that six key compounds, luteolin, apigenin, quercetin, kaempferol, ursolic acid, and oleanolic acid, contributed to the development of breast cancer by affecting the MMP9 and PPARG proteins. Integration of network pharmacology and bioinformatics revealed C. monogyna’s multitarget pharmacological mechanisms against breast cancer. This study provides convincing evidence that C. monogyna might partially alleviate breast cancer and ultimately lays a foundation for further experimental research on the anti-breast cancer activity of C. monogyna.

The therapeutic effectiveness of paliperidone in the treatment of schizophrenia has been limited by its poor oral bioavailability; hence, an alternative route could be appropriate. This study investigates the feasibility of developing a buccal film impregnated with paliperidone-loaded nanostructured lipid carriers (NLCs) and assesses the potential to enhance its bioavailability. Box–Behnken-based design optimization of NLCs was performed by examining the particles’ physical characteristics. The polymeric film was used to load optimized NLCs, which were then assessed for their pharmaceutical properties, permeability, and pharmacokinetics. The optimization outcomes indicated that selected formulation variables had a considerable (p < 0.05) impact on responses such as particle size, entrapment efficiency, and % drug release. Desired characteristics such as a negative charge, higher entrapment efficiency, and nanoparticles with ideal size distribution were shown by optimized NLC dispersions. The developed film demonstrated excellent physico-mechanical properties, appropriate texture, good drug excipient compatibility (chemically stable formulation), and amorphous drug nature. A sustained Weibull model drug release (p < 0.0005) and superior flux (~5-fold higher, p < 0.005) were seen in NLC-loaded film compared to plain-drug-loaded film. The pharmacokinetics profile in rabbits supports the goal of buccal therapy as evidenced by significantly higher AUC0–12 (p < 0.0001) and greater relative bioavailability (236%) than the control. These results support the conclusion that paliperidone-loaded NLC buccal film has the potential to be an alternate therapy for its effective administration in the treatment of schizophrenia.

Leflunomide (LEF), a disease-modifying anti-rheumatic drug, has been widely explored for its anti-inflammatory potential in skin disorders such as psoriasis and melanoma. However, its poor stability and skin irritation pose challenges for topical delivery. To surmount these issues, LEF-loaded solid lipid nanoparticles (SLNs) integrated with hydrogels have been developed in the present investigation. SLNs developed by microemulsion techniques were found ellipsoidal with 273.1 nm particle size and −0.15 mV zeta potential. Entrapment and total drug content of LEF-SLNs were obtained as 65.25 ± 0.95% and 93.12 ± 1.72%, respectively. FTIR and XRD validated the successful fabrication of LEF-SLNs. The higher stability of LEF-SLNs (p < 0.001) compared to pure drug solution was observed in photostability studies. Additionally, in vitro anti-inflammatory activity of LEF-SLNs showed good potential in comparison to pure drugs. Further, prepared LEF-SLNs loaded hydrogel showed ideal rheology, texture, occlusion, and spreadability for topical drug delivery. In vitro release from LEF-SLN hydrogel was found to follow the Korsmeyer-Peppas model. To assess the skin safety of fabricated lipidic formulation, irritation potential was performed employing the HET-CAM technique. In conclusion, the findings of this investigation demonstrated that LEF-SLN hydrogel is capable of enhancing the photostability of the entrapped drug while reducing its skin irritation with improved topical delivery characteristics.

The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1–E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol®) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol®, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (p-0.0001) and enhancer concentration (p-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (p < 0.0001) enhancement in the permeation (~78.59 µg/cm2) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of Trichophyton mentagrophyte. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis.

Background: The combination of two drugs celecoxib + tramadol and diclofenac sodium + tramadol with different mechanisms of action is better for achieving effective pain control. Materials and Methods: The simple reproducible mathematically modified UV spectroscopic methods were established for concomitant evaluation of the binary combination of celecoxib + tramadol and diclofenac sodium + tramadol formulations. The first technique is predicated on separating the pure zero-order spectra of TDL and CCB from the mixture spectra and quantification at their lambda max. The second and third method involves the ratio absorption difference and ratio first derivative spectroscopic method for quantification of DFS and TDL. Additionally, we followed ICH guidelines to validate these approaches for specificity, accuracy, and precision. Results: Both formulations were effectively analyzed using the proposed methods, with results falling into the series of 2-50 μg/mL for TDL, and 1-30 μg/mL for DFS and CCB. The good recovery of 98.56% -101.48% with low relative error and percentage relative standard deviation verified the methodologies' correctness and repeatability. Finally, proposed mathematically modified spectroscopic procedures were exploited for quality control of analytes from formulation and manually prepared mixtures. The determination of % of retrieval of an added known quantity of authentic medications of CCB, TDL, and DFS to the powdered pill served as additional evidence of correctness. Conclusion: The established UV spectroscopic techniques are simple, rapid, and perfect for simultaneous quantification of CCB, DSF, and TDL from the solid dosage forms. The assay results also confirmed the nonexistence of tablet adjuvants intervention in the quantification of medicines in the tablets Therefore, these approaches can be utilized for systematic quantification of these drugs in the binary formulations without chemical separation. [ABSTRACT FROM AUTHOR]

A series of 1,2,3-trisubstituted indolizines (2a–2f, 3a–3d, and 4a–4c) were screened for in vitro whole-cell anti-tubercular activity against the susceptible H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 2b–2d, 3a–3d, and 4a–4c were active against the H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas the indolizines 4a–4c, with ethyl ester group at the 4-position of the benzoyl ring also exhibited anti-MDR-MTB activity (MIC = 16–64 µg/mL). In silico docking study revealed the enoyl-acyl carrier protein reductase (InhA) and anthranilate phosphoribosyltransferase as potential molecular targets for the indolizines. The X-ray diffraction analysis of the compound 4b was also carried out. Further, a safety study (in silico and in vitro) demonstrated no toxicity for these compounds. Thus, the indolizines warrant further development and may represent a novel promising class of InhA inhibitors and multi-targeting agents to combat drug-sensitive and drug-resistant MTB strains.

Administration of almotriptan as an oral therapy is largely limited because of poor aqueous solubility and rather low bioavailability. The aim of present investigation was to formulate oral mucoadhesive film of almotriptan to improve the drug delivery and desired therapeutic effects. Placebo films (F1-F8) were prepared by varying the concentrations of Proloc 15 (7.5-15% w/v) and Eudragit RL 100/RS 100 (15-30% w/v) polymers. Physicomechanical and pharmaceutical characteristics of drug loaded films (FA1-FA4) were examined. Selected FA4 film was evaluated in vivo by assessing the pharmacokinetic profile and compared with oral therapy in rabbits. FA1-FA4 films exhibited excellent physicomechanical properties and rapid hydration. A biphasic and considerably greater drug release (p 2 folds, p

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has thrown a challenge to the scientific community. Several interventions to stop or limit the spread of infection have failed, and every time the virus emerges, it becomes more contagious and more deadly. Vaccinating a significant proportion of the population is one of the established methods to achieve herd immunity. More than 100 COVID-19 vaccines have been designed and tested against the virus. The development of a new vaccine takes years of testing, but due to the pandemic, healthcare authorities have given emergency use authorization for a few vaccines. Among them are BioNTech and Moderna vaccines (mRNA based); ChAdOx1, Gam-COVID-Vac, Janssen vaccines (vector-based); CoronaVac, COVAXIN (virus inactivated); and EpiVacCorona vaccine (viral peptide). Mixtures of vaccines are also being tested to evaluate their efficacy against mutant strains of SARS-CoV-2. All these vaccines in clinical trials have shown robust production of neutralizing antibodies sufficient to prevent infection. Some of the vaccinated people reported serious complications. However, no definitive relationship could be established between vaccination administration and the occurrence of these complications. None of the COVID-19 vaccines approved to date have been found to be effective against all of the SARS-CoV-2 variants.

A series of previously synthesized 5-benzyliden-2-(5-methylthiazole-2-ylimino)thiazoli- din-4-one were evaluated for their anti-inflammatory activity on the basis of PASS predictive outcomes. The predictive compounds were found to demonstrate moderate to good anti-inflammatory activity, and some of them displayed better activity than indomethacin used as the reference drug. Structure–activity relationships revealed that the activity of compounds depends not only on the nature of the substituent but also on its position in the benzene ring. The most active compounds were selected to investigate their possible mechanism of action. COX and LOX activity were determined and found that the title compounds were active only to COX-1 enzymes with an inhibitory effect superior to the reference drug naproxen. As for LOX inhibitory activity, the derivatives failed to show remarkable LOX inhibition. Therefore, COX-1 has been identified as the main molecular target for the anti-inflammatory activity of our compounds. The docking study against COX-1 active site revealed that the residue Arg 120 was found to be responsible for activity. In summary, the 5-thiazol-based thiazolidinone derivatives have been identified as a novel class of selective COX-1 inhibitors.

Sesamol (SES) possesses remarkable chemotherapeutic activity, owing to its anti-inflammatory and antioxidant potential. However, the activity of SES is mainly hampered by its poor physicochemical properties and stability issues. Hence, to improve the efficacy of this natural anti-inflammatory and cytotoxic agent, it was loaded into β-cyclodextrin nanosponges (NS) prepared using different molar ratios of polymer and crosslinker (diphenyl carbonate). The particle size of SES-laden NS (SES-NS) was shown to be in the nano range (200 to 500 nm), with a low polydispersity index, an adequate charge (−17 to −26 mV), and a high payload. Field emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the bioactive-loaded selected batch (SES-NS6). This batch of nanoformulations showed improved solubilization efficacy (701.88 µg/mL) in comparison to bare SES (244.36 µg/mL), polymer (β-CD) (261.43 µg/mL), and other fabricated batches. The drug release data displayed the controlled release behavior of SES from NS. The findings of the egg albumin denaturation assay revealed the enhanced anti-inflammatory potential of SES-NS as compared to bare SES. Further, the cytotoxicity assay showed that SES-NS was more effective against B16F12 melanoma cell lines than the bioactive alone. The findings of this assay demonstrated a reduction in the IC50 values of SES-NS (67.38 μg/mL) in comparison to SES (106 μg/mL). The present investigation demonstrated the in vitro controlled release pattern and the enhanced anti-inflammatory and cytotoxic activity of SES-NS, suggesting its potential as a promising drug delivery carrier for topical delivery.

A brand-new nano-crystal (NC) version of the hydrophobic drug Paclitaxel (PT) were formulated for cancer treatment. A stable NC formulation for the administration of PT was created using the triblock co-polymer Pluronic F127. To achieve maximum entrapment effectiveness and minimal particle size, the formulation was improved using the central composite design by considering agitation speed and vacuum pressure at five levels (coded as +1.414, +1, 0, −1, and −1.414). According to the Design Expert software’s predictions, 13 runs were created and evaluated for the chosen responses. The formulation prepared with an agitation speed of 1260 RPM and a vacuum pressure of 77.53 mbar can meet the requirements of the ideal formulation in order to achieve 142.56 nm of PS and 75.18% EE, according to the level of desirability (D = 0.959). Folic acid was conjugated to Pluronic F127 to create folate receptor-targeted NC. The drug release profile of the nano-crystals in vitro demonstrated sustained release over an extended period. Folate receptor (FR)-targeted NC (O-PT-NC-Folate) has also been prepared by conjugating folic acid to Pluronic F127. MTT test is used to validate the targeting efficacy on the FR-positive human oral cancer cell line (KB). At pharmacologically relevant concentrations, the PT nano-crystal formulation did not cause hemolysis. Compared to non-targeted NC of PT, the O-PT-NC-Folate showed a comparable but more sustained anti-cancer effect, according to an in vivo anti-tumor investigation in NCI/ADR-RES cell lines. The remarkable anti-tumor effectiveness, minimal toxicity, and simplicity of scale-up manufacturing of the NC formulations indicate their potential for clinical development. Other hydrophobic medications that are formulated into nano-systems for improved therapy may benefit from the formulation approach.

Currently, gastro-retentive dosage forms achieved a remarkable position among the oral drug delivery systems. This is a broadly used technique to hold the drug delivery systems for a long duration in the gastro intestine (GI) region, slow drug delivery, and overcome other challenges related to typical oral delivery such as low bioavailability. The current work aimed to formulate and characterize a new expandable gastro-retentive system through Itopride Hydrochloride (IH)’s unfolding process for controlled release. The IH-loaded unfolding film formulation was optimized using the Box-Behnken design for folding endurance and length of tested layer (LTL). Initially, the formulation was made using several anti-adhesive additives to promote the unfolding mechanism. Citric acid and sodium bicarbonate were selected as anti-adhesives based on these results. The enfolded film in a capsule shell was shown to unroll in the stomach fluids and render drug delivery up to 12 h in acidic conditions. A fabricated system should have dimensions more than the size of the relaxed pyloric sphincter, and as required, >20 mm LTL was identified. This further confirms that the residence period in the stomach is irrelevant to the fed or fasted condition. Based on desirability criteria, the formulation containing 143.83, 0.7982, and 14.6096 Eudragit L100, PEG, and sodium bicarbonate are selected as optimized formulations (O-IH-UF). The optimized formulation was further analyzed for various parameters such as tensile strength, mechanical strength, unfolding nature, degradability, and in vitro release studies. The pharmacokinetic study revealed greater AUC (area under the curve) and long half-life with the designed O-IH-UF formulation, confirming that the unfolding film type can be a favorable drug system for enhancing the bioavailability of low soluble drugs. The results showed that unfolding types of gastro retentive systems could potentiate the drugs with stability issues in an alkaline medium or those with absorption in acidic conditions.

As regulatory and technical landscapes for pharmaceutical formulation development are rapidly evolving, a risk-management approach using multivariate analysis is highly essential for designing a product with requisite critical quality attributes (CQA). Efinaconazole, a newly approved poorly water-soluble antifungal triazole drug has poor permeability. Spanlastics, new-generation surfactant nanovesicles, being fluidic, help improve the permeability of drugs. Therefore, we optimized efinaconazole spanlastics using the concepts of Formulation-by-Design (FbD) and explored the feasibility of transungual delivery for the management of onychomycosis. Using the Ishikawa fishbone diagram, the risk factors that may have an impact on the CQA of efinaconazole spanlastic vesicles were identified. Application of the Plackett–Burman experimental design facilitated the screening of eight different formulation and process parameters influencing particle size, transmittance, relative deformability, zeta potential, entrapment efficiency, and dissolution efficiency. With the help of Pareto charts, the three most significant factors were identified, viz., vesicle builder (Span), edge activator (Tween), and mixing time. The levels of these three critical variables were optimized by FbD to reduce the particle size and maximize the transparency, relative deformability, encapsulation efficiency, and dissolution efficiency of efinaconazole spanlastic nanovesicles. Bayesian and Lenth’s analysis and mathematical modeling of the experimental data helped to quantify the critical formulation attributes required for getting the formulation with optimum quality features. The optimized efinaconazole-loaded spanlastic vesicles had a particle size of 197 nm, transparency of 91%, relative deformability of 12.5 min, and dissolution efficiency of 81.23%. The spanlastic formulation was incorporated into a gel and explored ex vivo for transungual delivery. This explorative study provides an example of the application of principles of risk management, statistical multivariate analysis, and the FbD approach in developing efinaconazole spanlastic nanovesicles.

A series of 2,3-dihydroquinazolin-4(1H)-one derivatives (3a–3m) was screened for in vitro whole-cell antitubercular activity against the tubercular strain H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 3l and 3m with di-substituted aryl moiety (halogens) attached to the 2-position of the scaffold showed a minimum inhibitory concentration (MIC) of 2 µg/mL against the MTB strain H37Rv. Compound 3k with an imidazole ring at the 2-position of the dihydroquinazolin-4(1H)-one also showed significant inhibitory action against both the susceptible strain H37Rv and MDR strains with MIC values of 4 and 16 µg/mL, respectively. The computational results revealed the mycobacterial pyridoxal-5′-phosphate (PLP)-dependent aminotransferase (BioA) enzyme as the potential target for the tested compounds. In vitro, ADMET calculations and cytotoxicity studies against the normal human dermal fibroblast cells indicated the safety and tolerability of the test compounds 3k–3m. Thus, compounds 3k–3m warrant further optimization to develop novel BioA inhibitors for the treatment of drug-sensitive H37Rv and drug-resistant MTB.

Considering the importance of benzothiazepine pharmacophore, an attempt was carried out to synthesize novel 1,5-benzothiazepine derivatives using polyethylene glycol-400 (PEG-400)-mediated pathways. Initially, different chalcones were synthesized and then subjected to a cyclization step with benzothiazepine in the presence of bleaching clay and PEG-400. PEG-400-mediated synthesis resulted in a yield of more than 95% in less than an hour of reaction time. Synthesized compounds 2a–2j were investigated for their in vitro cytotoxic activity. Moreover, the same compounds were subjected to systematic in silico screening for the identification of target proteins such as human adenosine kinase, glycogen synthase kinase-3β, and human mitogen-activated protein kinase 1. The compounds showed promising results in cytotoxicity assays; among the tested compounds, 2c showed the most potent cytotoxic activity in the liver cancer cell line Hep G-2, with an IC50 of 3.29 ± 0.15 µM, whereas the standard drug IC50 was 4.68 ± 0.17 µM. In the prostate cancer cell line DU-145, the compounds displayed IC50 ranges of 15.42 ± 0.16 to 41.34 ± 0.12 µM, while the standard drug had an IC50 of 21.96 ± 0.15 µM. In terms of structural insights, the halogenated phenyl substitution on the second position of benzothiazepine was found to significantly improve the biological activity. This characteristic feature is supported by the binding patterns on the selected target proteins in docking simulations. In this study, 1,5-benzothiazepines have been identified as potential anticancer agents which can be further exploited for the development of more potent derivatives.

The present research was aimed to develop a terbinafin hydrochloride (TH)-encapsulated solid lipid nanoparticles (SLNs) hydrogel for improved antifungal efficacy. TH-loaded SLNs were obtained from glyceryl monostearate (lipid) and Pluronic® F68 (surfactant) employing high-pressure homogenization. The ratio of drug with respect to lipid was optimized, considering factors such as desired particle size and highest percent encapsulation efficiency. Lyophilized SLNs were then incorporated in the hydrogel prepared from 0.2–1.0% w/v carbopol 934P and further evaluated for rheological parameters. The z-average, zeta potential and polydispersity index were found to be 241.3 nm, −15.2 mV and 0.415, respectively. The SLNs show a higher entrapment efficiency of about 98.36%, with 2.12 to 6.3602% drug loading. SEM images, XRD and the results of the DSC, FTIR show successful preparation of SLNs after freeze drying. The TH-loaded SLNs hydrogel showed sustained drug release (95.47 ± 1.45%) over a period of 24 h. The results reported in this study show a significant effect on the zone of inhibition than the marketed formulation and pure drug in Candida albicans cultures, with better physical stability at cooler temperatures. It helped to enhance skin deposition inthe ex vivostudy and improved, in vitro and in vivo, the antifungal activity.

In situ gels have been extensively explored as ocular drug delivery system to enhance bioavailability and efficacy. The objective of present study was to design, formulate and evaluate ion-activated in situ gel to enhance the ocular penetration and therapeutic performance of moxifloxacin in ophthalmic delivery. A simplex lattice design was utilized to examine the effect of various factors on experimental outcomes of the in situ gel system. The influence of polymers (independent variables) such as gellan gum (X1), sodium alginate (X2), and HPMC (X3) on gel strength, adhesive force, viscosity and drug release after 10 h (Q10) were assessed. Selected formulation (MH7) was studied for ex vivo permeation, in vivo irritation and pharmacokinetics in rabbits. Data revealed that increase in concentration of polymers led to higher gel strength, adhesive force and viscosity, however, decreases the drug release. MH7 exhibited all physicochemical properties within acceptable limits and was stable for 6 months. Release profile of moxifloxacin from MH7 was comparable to the check point batches and followed Korsmeyer-Peppas matrix diffusion-controlled mechanism. Ocular irritation study signifies that selected formulation is safe and non-irritant for ophthalmic administration. In vivo pharmacokinetics data indicates significant improvement of moxifloxacin bioavailability (p < 0.0001) from MH7, as evidenced by higher Cmax (727 ± 56 ng/ml) and greater AUC (2881 ± 108 ng h/ml), when compared with commercial eye drops (Cmax; 503 ± 85 ng/ml and AUC; 978 ± 86 ng h/ml). In conclusion, developed in situ gel system (MH7) could offers a more effective and extended ophthalmic therapy of moxifloxacin in ocular infections when compared to conventional eye drops.

The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the feasibility of brain targeting through the intranasal route. Preliminary batches (F1–F9) were prepared and evaluated for various pharmaceutical characteristics. A full factorial design of the experiment was applied to optimize and assess the effect of two influencing variables (Carbopol 934P (X1) and Poloxamer 407 (X2)) on the response effects (gelation temperature (Y1) and % drug release (Y2) at 8 h). The data demonstrate that both influencing variables affect the response variables significantly (p < 0.05). The optimized formulation (F7) exhibited favorable rheological properties, adequate mucoadhesion, sustained drug release, and greater permeation across the nasal mucosa. An in vitro ciliotoxicity study confirms the nontoxicity of the optimized in situ gel (D7) on the nasal mucosa. An in vivo pharmacokinetic study in rats was performed to assess drug targeting to the brain following the nasal application of the selected in situ gel (D7). Significantly higher (p < 0.0001) Cmax (~4-fold) and AUC0-α (~3.5-fold) values were noticed in the brain after nasal application, as compared to the intravenous route. However, less systemic exposure to darunavir was noticed with nasal therapy, which confirms the low absorption of the drug into the central compartment. Overall, the data here demonstrate that the optimized in situ mucoadhesive nasal gel is effective in targeting darunavir to the brain by the nasal route and could be a viable option for the treatment of NeuroAIDS.

A rapid and reproducible hydrophilic liquid chromatography (HILIC) process was established for concomitant determination of remogliflozin etabonate (RE), vildagliptin (VD), and metformin (MF) in a formulation. A face-centered central composite experimental design was employed to optimize and predict the chromatographic condition by statistically studying the surface response model and design space with desirability close to one. A HILIC column with a simple mobile phase of acetonitrile (65% v/v) and 20 mM phosphate buffer (35% v/v, pH 6, controlled with orthophosphoric acid) was used to separate RE, VD, and MF. RE, VD, and MF were separated in 3.6 min using an isocratic mode mobile phase flow at a flow rate of 1.4 mL at room temperature, and the analytes were examined by recording the absorption at 210 nm. The developed HILIC method was thoroughly validated for all parameters recommended by ICH, and linearity was observed in the ranges 20–150 µg/mL, 10–75 µg/mL, and 50–750 µg/mL for RE, VD, and MF, respectively, along with excellent regression coefficients (r2 > 0.999). The calculated percentage relative deviation and relative error ascertained the precision and accuracy of the method. The selectivity and accuracy were further confirmed by the high percentage recovery of added standard drugs to the formulation using the standard addition technique. The robustness of the HILIC processes was confirmed by developing a half-normal probability plot and Pareto chart, as the slight variation of a single factor had no significant influence on the assay outcomes. Utilization of the optimized HILIC procedure for concurrent quantification of RE, VD, and MF in solid dosage forms showed accurate and reproducible results. Hence, the fast HILIC method can be regularly employed for the quality assurance of pharmaceutical preparations comprising RE, VD, and MF.

Non-small cell lung cancer, a molecularly diverse disease, is the most prevalent cause of cancer mortality globally. Increasing understanding of the clinicopathology of the disease and mechanisms of tumor progression has facilitated early detection and multimodal care. Despite the advancements, survival rates are extremely low due to non-targeted therapeutics and correspondingly increased risk of metastasis. At some phases of cancer, patients need to face the ghost of chemotherapy. It is a difficult decision near the end of life. Such treatments have the capability to prolong survival or reduce symptoms, but can cause serious adverse effects, affecting quality of life of the patient. It is evident that many patients do not die from burden of the disease alone, but they die due to the toxic effect of treatment. Thus, increasing the efficacy is one aspect and decreasing the toxicity is another critical aspect of cancer formulation design. Through our current research, we tried to uncover both mentioned potentials of the formulation. Therefore, we designed actively targeted nanoparticles for improved therapeutics considering the overexpression of adenosine (ADN) receptors on non-small cell lung cancer (NSCLC) cells. Docetaxel (DTX), an essential therapeutic as part of combination therapy or as monotherapy for the treatment of NSCLC, was encapsulated in biodegradable poly(lactic-co-glycolic acid) nanoparticles. ADN was conjugated on the surface of nanoparticles using EDC-NHS chemistry. The particles were characterized in vitro for physicochemical properties, cellular uptake, and biocompatibility. The size and zeta potential of DTX nanoparticles (DPLGA) were found to be 138.4 ± 5.45 nm and −16.7 ± 2.3 mV which were found to change after ADN conjugation. The size was increased to 158.2 ± 6.3 nm, whereas zeta potential was decreased to −11.7 ± 1.4 mV for ADN-conjugated DTX nanoparticles (ADN-DPLGA) indicative of surface conjugation. As observed from transmission electron microscopy (TEM), the nanoparticles were spherical and showed no significant change in encapsulation efficiency even after surface conjugation. Careful and systematic optimization leads to ADN-conjugated PLGA nanoparticles having distinctive characteristic features such as particle size, surface potential, encapsulation efficacy, etc., that may play crucial roles in the fate of nanoparticles (NPs). Consequently, higher cellular uptake in the A549 lung cancer cell line was exhibited by ADN-DPLGA compared to DPLGA, illustrating the role of ADN receptors (ARs) in facilitating the uptake of NPs. Further in vivo pharmacokinetics and tissue distribution experiments revealed prolonged circulation in plasma and significantly higher lung tissue distribution than in other organs, dictating the targeting potential of the developed formulation over naïve drug and unconjugated formulations. Further, in vivo acute toxicity was examined using multiple parameters for non-toxic attributes of the developed formulation compared to other non-targeted organs. Further, it also supports the selection of biocompatible polymers in the formulation. The current study presents a proof-of-concept for a multipronged formulation technology strategy that might be used to maximize anticancer therapeutic responses in the lungs in the treatment of NSCLC. An improved therapeutic and safety profile would help achieve maximum efficacy at a reduced dose that would eventually help reduce the toxicity.

Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito Anopheles arabiensis, a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion. A preliminary study of the structure–activity relationship indicated that the electron-withdrawing substituent in the para position of the 4-phenyl-pyrimidinone moiety enhanced the molecules’ potency. A docking study of these derivatives revealed favorable binding affinity for the sterol carrier protein-2 receptor, a protein present in the intestine of the mosquito larvae. Being effective insecticides against the malaria-transmitting Anopheles arabiensis, 1,2,3-triazole-based pyrimidinones represent a starting point to develop novel inhibitors of insect growth regulators.

A combination of antibiotics and antiprotozoal and antisecretory medicines has been prescribed for the treatment of diarrhea. A rapid, reproducible liquid chromatographic procedure was established for the concurrent analysis of metronidazole (MET), ofloxacin (OFL), and racecadotril (RAC) in suspension. The Box–Behnken design, a full factorial multivariate optimization technique, was utilized to optimize chromatographic parameters with fewer runs. The separation of MET, OFL, and RAC was accomplished within 3.2 min, using a Zorbax C18 high-performance liquid chromatography column with a simple mobile phase comprising acetonitrile (55 vol.%): methanol (10 vol.%):20 mM phosphate buffer (35 vol.%, pH 6, regulated with ortho-phosphoric acid). The mobile phase was pumped in the isocratic mode at a rate of 1.4 mL/min at ambient temperature. Analytes were monitored by adjusting the wavelength at 295 nm for MET and OFL and 231 nm for RAC. Validation of the proposed HPLC method exhibited linearity in the concentration of 20–250 µg/mL, 10–150 µg/mL, and 5–80 µg/mL for MET, OFL, and RAC respectively, along with an excellent regression coefficient (r2 > 0.999). The accuracy and precision of the chromatographic procedure were also evidenced by the low percent relative error and relative standard deviation. A Pareto chart developed by the two-factor interaction (2FI) study confirmed that the method was robust, as the slight variation in a single factor had no significant influence on the assay outcomes. Lastly, the developed HPLC process was utilized for the concurrent quantification of MET, OFL, and RAC in liquid oral preparation. Furthermore, when the assay results were compared to the described techniques, it was discovered that there was no significant difference in the accuracy and precision of the results. Hence, the developed rapid HPLC method could be employed for the quality control study of a preparation comprising of MET, OFL, and RAC in industries and regulatory authority laboratories.

The present investigation demonstrates renewable cardanol-based polyol for the formulation of nanocomposite polyurethane (PU) coatings. The functional and structural features of cardanol polyol and nanoparticles were studied using FT-IR and 1H NMR spectroscopic techniques. The magnetic hydroxyapatite nanoparticles (MHAPs) were dispersed 1–5% in PU formulations to develop nanocomposite anticorrosive coatings. An increase in the strength of MHAP increased the anticorrosive performance as examined by immersion and electrochemical methods. The nanocomposite PU coatings showed good coating properties, viz., gloss, pencil hardness, flexibility, cross-cut adhesion, and chemical resistance. Additionally, the coatings were also studied for surface morphology, wetting, and thermal properties by scanning electron microscope (SEM), contact angle, and thermogravimetric analysis (TGA), respectively. The hydrophobic nature of PU coatings increased by the addition of MHAP, and an optimum result (105°) was observed in 3% loading. The developed coatings revealed its hydrophobic nature with excellent anticorrosive performance.

The present work aimed to develop a chronotherapeutic system of valsartan (VS) using nanocrystal formulation to improve dissolution. VS nanocrystals (VS-NC) were fabricated using modified anti-solvent precipitation by employing a Box–Behnken design to optimize various process variables. Based on the desirability approach, a formulation containing 2.5% poloxamer, a freezing temperature of −25 °C, and 24 h of freeze-drying time can fulfill the optimized formulation’s requirements to result in a particle size of 219.68 nm, 0.201 polydispersity index, and zeta potential of −38.26 mV. Optimized VS-NC formulation was compressed (VNM) and coated subsequently with ethyl cellulose and HPMC E 5. At the same time, fast dissolving tablets of VS were designed, and the best formulation was loaded with VNM into a capsule size 1 (average fill weight—400–500 mg, lock length—19.30 mm, external diameter: Cap—6.91 mm; Body—6.63 mm). The final tab in cap (tablet-in-capsule) system was studied for in vitro dissolution profile to confirm the chronotherapeutic release of VS. As required, a bi-pulse release of VS was identified with a lag time of 5 h. The accelerated stability studies confirmed no significant changes in the dissolution profiles of the tab in cap system (f2 similarity profile: >90). To conclude, the tab in cap system was successfully developed to induce a dual pulsatile release, which will ensure bedtime dosing with release after a lag-time to match with early morning circadian spikes.

The purpose of the present research work was to design, optimize, and evaluate fluvastatin-loaded solid lipid nanoparticles (FLV-SLNPs) using 32 factorial design for enhancing the bioavailability. Fluvastatin has several disadvantages, including the low solubility and substantial first-pass metabolism resulting in a low (30%) bioavailability and a short elimination half-life. FLV-SLNPs were prepared using the nano-emulsion technique. For the optimization of the FLV-SLNPs, a total of nine formulations were prepared by varying two independent factors at three levels, using full factorial design. In this design, lipid (A) and surfactant (B) concentrations were chosen as independent factors, whereas entrapment efficiency (Y1) and in-vitro drug release (Y2) were selected as the dependent variables. Additionally, the prepared SLNPs were characterized for X-ray diffraction, Fourier transform-infrared spectroscopy, and differential scanning calorimetry. These studies revealed that there were no interactions between the drug and the selected excipients and the selected formulation components are compatible with the drug. Pharmacokinetic studies in rats confirmed significant improvement in AUC and MRT of SLNPs in comparison with the pure drug indicating the enhanced bioavailability of SLNPs. This study provides a proof-of-concept for the fact that SLNPs can be effectively developed via experimental factorial design, which requires relatively minimal experimentation.

Dermal disorders such as psoriasis and eczema are associated with modifications in the chemical and molecular composition of the skin. Clobetasol propionate (CP), a superpotent topical glucocorticoid, is widely used for the therapeutic management of various skin conditions, owing to its strong anti-inflammatory, antipruritic, vasoconstrictive, and antiproliferative activities. Safety studies demonstrated that CP is safer for a shorter period, however, with prolonged application, it shows secondary side effects such as photosensitivity, Cushing-like syndrome, allergic contact dermatitis, osteonecrosis, hypopigmentation, steroid acne, and skin atrophy. Therefore, the US FDA (United States Food and Drug Administration) has restricted the usage of CP to not more than 15 days. Research scientists addressed its several formulations and drug delivery issues, such as low water solubility, less stability, photodegradation, and poor absorption, by incorporating them into novel nanobased delivery platforms. With the utilization of these technologies, these drawbacks of CP have been resolved to a large extent to reestablish this moiety. This article explores the physicochemical properties and mechanism of action of CP. Additionally, an attempt has been made to discover and highlight the possible features of the novel nanosystems, including nanoemulsions, nanosponges, solid lipid nanoparticles, nanostructured lipid carriers, and nanogels, reported for CP. The stability and safety concerns of CP, along with its commercial status, are also discussed.

Due to complicated anatomical and physical properties, targeted drug delivery to ocular tissues continues to be a key challenge for formulation scientists. Various attempts are currently being made to improve the in vivo performance of therapeutic molecules by encapsulating them in various nanocarrier systems or devices and administering them via invasive/non-invasive or minimally invasive drug administration methods. Biocompatible and biodegradable lipid nanoparticles have emerged as a potential alternative to conventional ocular drug delivery systems to overcome various ocular barriers. Lipid-based nanocarrier systems led to major technological advancements and therapeutic advantages during the last few decades of ocular therapy, such as high precorneal residence time, sustained drug release profile, minimum dosing frequency, decreased drug toxicity, targeted site delivery, and, therefore, an improvement in ocular bioavailability. In addition, such formulations can be given as fine dispersion in patient-friendly droppable preparation without causing blurred vision and ocular sensitivity reactions. The unique advantages of lipid nanoparticles, namely, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and liposomes in intraocular targeted administration of various therapeutic drugs are extensively discussed. Ongoing and completed clinical trials of various liposome-based formulations and various characterization techniques designed for nanoemulsion in ocular delivery are tabulated. This review also describes diverse solid lipid nanoparticle preparation methods, procedures, advantages, and limitations. Functionalization approaches to overcome the drawbacks of lipid nanoparticles, as well as the exploration of new functional additives with the potential to improve the penetration of macromolecular pharmaceuticals, would quickly progress the challenging field of ocular drug delivery systems.

The aim of this study was to develop a fast RP-HPLC method for simultaneous measurement of two antidiabetic formulations (vildagliptin + remogliflozin and teneligliptin + remogliflozin) under identical experimental conditions. Using the Box–Behnken approach and response surface design, the interaction and quadratic influence of three variable parameters, acetonitrile %, pH of the mobile phase, and flow rate, on resolution between the peaks were optimized. To forecast the resolution of peaks (2.7 and 6.5) for the three anti-diabetic medications, the design space with desirability function was used to find the optimal chromatographic conditions. Isocratic elution with 58:42 acetonitrile and phosphate buffer (20 mM KH2PO4, pH adjusted to 4.9 with orthophosphoric acid) over a Zorabx C18 HPLC column with a flow rate of 1.2 mL min−1 separated all three analytes in 2.5 min. In addition, the optimized HPLC process was validated using ICH recommendations. The devised HPLC method’s precision and accuracy were proven by the low percent relative standard deviation (0.60–1.65%), good percentage recovery (98.18–101.50%), and low percentage relative errors (0.20–1.82%). The method’s robustness was also proven by slightly varying the five separate parameters. Finally, the accuracy of the proposed HPLC approach was confirmed using a standard addition method for simultaneous determination of vildagliptin + remogliflozin and teneligliptin + remogliflozin from formulations. Furthermore, the findings demonstrated that experimental design can be successfully used to optimize chromatographic conditions with fewer runs. The devised HPLC method for simultaneous quantification of two binary combinations utilizing the same chromatographic conditions is fast, accurate, precise, and easy, and it might be utilized in laboratories for routine quality control investigations on both formulations.

Being a biopharmaceutics classification system class II drug, the absorption of sertraline from the gut is mainly limited by its poor aqueous solubility. The objective of this investigation was to improve the solubility of sertraline utilizing self-nanoemulsifying drug delivery systems (SNEDDS) and developing it into a tablet dosage form. Ternary phase diagrams were created to identify nanoemulsion regions by fixing oil (glycerol triacetate) and water while varying the surfactant (Tween 80) and co-surfactant (PEG 200) ratio (Smix). A three-factor, two-level (23) full factorial design (batches F1–F8) was utilized to check the effect of independent variables on dependent variables. Selected SNEDDS (batch F4) was solidified into powder by solid carrier adsorption method and compressed into tablets. The SNEDDS-loaded tablets were characterized for various pharmaceutical properties, drug release and evaluated in vivo in Wistar rats. A larger isotropic region was noticed with a Smix ratio of 2:1 and the nanoemulsion exhibited good stability. Screening studies’ data established that all three independent factors influence the dependent variables. The prepared tablets displayed optimal pharmaceutical properties within acceptable limits. In vitro sertraline release demonstrated from solid SNEDDS was statistically significant (p < 0.0001) as compared to pure sertraline. Differential Scanning Calorimetry and X-Ray Diffraction data established the amorphous state of the drug in SNEDDS formulation, while FTIR spectra indicate the compatibility of excipients and drug. Pharmacokinetic evaluation of the SNEDDS tablet demonstrated significant increment (p < 0.0001) in AUC0-α (~5-folds), Cmax (~4-folds), and relative bioavailability (386%) as compared to sertraline suspension. The current study concludes that the solid SNEDDS formulation could be a practicable and effective strategy for oral therapy of sertraline.

Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe and effective non-invasive airway delivery that can reach deep alveoli, restore the surfactant function and reduce oxidative stress. We designed an endogenous surfactant-based liposomal delivery system of naringin to be delivered as an aerosol that supports pulmonary mechanics for the management of pulmonary fibrosis. Phosphatidylcholine-based liposomes showed 91.5 ± 2.4% encapsulation of naringin, with a mean size of 171.4 ± 5.8 nm and zeta potential of −15.5 ± 1.3 mV. Liposomes with the unilamellar structure were found to be spherical and homogeneous in shape using electron microscope imaging. The formulation showed surface tension of 32.6 ± 0.96 mN/m and was able to maintain airway patency of 97 ± 2.5% for a 120 s test period ensuring the effective opening of lung capillaries and deep lung delivery. In vitro lung deposition utilizing Twin Stage Impinger showed 79 ± 1.5% deposition in lower airways, and Anderson Cascade Impactor deposition revealed a mass median aerodynamic diameter of 2.35 ± 1.02 μm for the aerosolized formulation. In vivo efficacy of the developed formulation was analyzed in bleomycin-induced lung fibrosis model in rats after administration by the inhalation route. Lactate dehydrogenase activity, total protein content, and inflammatory cell infiltration in broncho-alveolar lavage fluid were substantially reduced by liposomal naringin. Oxidative stress was minimized as observed from levels of antioxidant enzymes. Masson’s Trichrome staining of lung tissue revealed significant amelioration of histological changes and lesser deposition of collagen. Overall results indicated the therapeutic potential of the developed non-invasive aerosol formulation for the effective management of pulmonary fibrosis.

The COVID-19 infection caused by the new SARS-CoV-2 virus has been linked to a broad spectrum of symptoms, from a mild cough to life-threatening pneumonia. As we learn more about this unusual COVID-19 epidemic, new issues are emerging and being reported daily. Mucormycosis, also known as zygomycosis or phycomycosis, causes severe fungal illness to individuals with a weakened immune system. It is a devastating fungal infection, and the most frequent kind is the rhino cerebral type. As a devastating second wave of COVID-19 sweeps India, doctors report several instances involving a strange illness—sometimes known as the “black fungus”—among returning and recovered COVID-19 patients. This paper analyzes the existing statistical data to address the severity of prevalence and further notes the nano-based diagnostic parameters, clinical presentations, its connection with other conditions like diabetes, hypertension, and GI disorders, and the importance of anti-fungal therapy in treating the same. Anti-fungal therapies, as well as surgical interventions, are currently used for the treatment of the disease. Proper and timely diagnosis is necessary, along with the reduction in the spread of COVID-19. From the review, it was found that timely pharmacologic interventions and early diagnosis by using a nano-based diagnostic kit can help control the disease. Additionally, this paper provides novel information about the nanotechnology approaches such as fungal detection biosensors, nucleic acids-based testing, point-of-care tests, and galactomannans detection, in the diagnosis of mucormycosis, and thereby reinforces the need for further research on the topic.

Topical therapy of antifungals is primarily restricted due to the low innate transport of drugs through the thick multi-layered keratinized nail plate. The objective of this investigation was to develop a gel formulation, and to optimize and evaluate the transungual delivery of terbinafine using the constant voltage iontophoresis technique. Statistical analysis was performed using Box–Behnken design to optimize the transungual delivery of terbinafine by examining crucial variables namely concentration of polyethylene glycol, voltage, and duration of application (2–6 h). Optimization data in batches (F1–F17) demonstrated that chemical enhancer, applied voltage, and application time have influenced terbinafine nail delivery. Higher ex vivo permeation and drug accumulation into the nail tissue were noticed in the optimized batch (F8) when compared with other batches (F1–F17). A greater amount of terbinafine was released across the nails when the drug was accumulated by iontophoresis than the passive counterpart. A remarkably higher zone of inhibition was observed in nails with greater drug accumulation due to iontophoresis, as compared to the passive process. The results here demonstrate that the optimized formulation with low voltage iontophoresis could be a viable and alternative tool in the transungual delivery of terbinafine, which in turn could improve the success rate of topical nail therapy in onychomycosis.

The advancement in therapy has provided a dramatic improvement in the rate of recovery among cancer patients. However, this improved survival is also associated with enhanced risks for cardiovascular manifestations, including hypertension, arrhythmias, and heart failure. The cardiotoxicity induced by chemotherapy is a life-threatening consequence that restricts the use of several chemotherapy drugs in clinical practice. This article addresses the prevalence of cardiotoxicity mediated by commonly used chemotherapeutic and immunotherapeutic agents. The role of susceptible genes and radiation therapy in the occurrence of cardiotoxicity is also reviewed. This review also emphasizes the protective role of antioxidants and future perspectives in anticancer drug-induced cardiotoxicities.