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Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/β-tricalcium phosphate (β-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications. [ABSTRACT FROM AUTHOR]

Natural-derived wound dressing products with on-demand antibacterial properties have recently captured accentuated attention in the application field of dermal wound treatment. Herein, an affordable approach to the fabrication of electrospun membranes employing polycaprolactone (PCL), Poloxamer 407 (POX), and Calophyllum inophyllum oil (CIO) for antibacterial dressings is demonstrated. Briefly, the influence of POX and CIO concentration on the obtained membranes is evaluated to determine the optimal parameters for dressing applications. The surface morphology, chemical compositions, surface wettability, moisture permeability, mechanical properties, and antibacterial activity of the obtained membranes are evaluated. The results show that the PCL_POX_CIO membranes exhibit the enlargement of fiber diameter, indicating a causal correlation between the PCL and CIO concentration. In addition, POX concentration is discovered to have a positive impact on water absorption capacity with recorded WCA of 0°, however, reduces mechanical strength due to bead formations. Specifically, when the CIO content reached 15 v/v%, the recorded inhibition zone was measured to be 15.7 ± 1.34 (mm). Furthermore, our study underscores the significant antibacterial activity of CIO in agar-diffusion tests against Staphylococcus aureus strains. Despite several limitations, the successful fabrication of the PCL_POX_CIO membranes open an economically sustainable approach for the scalable fabrication of antibacterial wound dressing. [ABSTRACT FROM AUTHOR]

Skin is the largest protective tissue of the body and is at risk of damage. Hence, the design and development of wound dressing materials is key for tissue repair and regeneration. Although silk fibroin is a known biopolymer in tissue engineering, its degradation rate is not correlated with wound closure rate. To address this disadvantage, we mimicked the hierarchical structure of skin and also provided antibacterial properties; a hydrogel with globular structure consisting of silk fibroin, pluronic F127, and curcumin was developed. In this regard, the effect of pluronic and curcumin on the structural and mechanical properties of the hydrogel was studied. The results showed that curcumin affected the particle size, crystallinity, and ultimate elongation of the hydrogels. In vitro assays confirmed that the hydrogel containing curcumin is not cytotoxic while the diffused curcumin and pluronic provided a considerable bactericidal property against Methicillin-resistant Staphylococcus aureus. Interestingly, presence of pluronic caused more than a 99% reduction in planktonic and adherent bacteria in the curcumin-free hydrogel groups. Moreover, curcumin improved this number further and inhibited bacteria adhesion to prevent biofilm formation. Overall, the developed hydrogel showed the potential to be used for skin tissue regeneration. [ABSTRACT FROM AUTHOR]

The formulation of paediatric medicines faces significant challenges to meet the requirements for safe and accurate administration, while maintaining a suitable taste. Multiparticulate formulations have a strong potential to address these challenges because they combine dose flexibility with ease of administration. Understanding the stability of multiparticulate formulations over storage as a function of time and environmental parameters, such as humidity and temperature, is important to manage their commercialisation and use. In this work, we have expanded the toolkit of available techniques for studying multiparticulates beyond those such as scanning electron microscopy (SEM) and confocal laser scanning microscopy. We include advanced methods of environmentally-controlled SEM to monitor temperature- and humidity-induced changes in-situ , and a variety of Raman spectroscopies including stimulated Raman scattering microscopy to identify and localise the different ingredients at the surface and inside the multiparticulates. These techniques allowed unprecedented monitoring of specific changes to the particulate structure and distribution of individual ingredients due to product aging. These methods should be considered as valuable novel tools for in-depth characterisation of multiparticulate formulations to further understand chemical changes occurring during their development, manufacturing and long-term storage. We envisage these techniques to be useful in furthering the development of future medicine formulations. [Display omitted] • Raman spectroscopy mapping of the surface of multiparticulates, with corresponding scanning electron microscopy (SEM) imaging to combine chemical and physical information. • Accelerated aging studies within environmental SEM (ESEM), combined with Raman spectroscopy point measurements to identify chemical and structural changes. • Stimulated Raman scattering (SRS) microscopy imaging to rapidly identify the location of the API and excipients across large particle populations. • Insights into the behaviour of poloxamer 407 and glyceryl dibehenate in multiparticulates when exposed to different environmental conditions. [ABSTRACT FROM AUTHOR]

The aqueous solution of binary mixtures of amphiphilic copolymers is a potential platform for fabricating mixed polymeric micelles for pharmaceutical applications, particularly in developing drug delivery depots for a poorly water-soluble compound. This study fabricated and investigated binary mixtures of poloxamer 403 (P403) and poloxamer 407 (P407) at varying P403:P407 molar ratios to develop a vehicle for the poorly water-soluble compound, using ibuprofen as a model drug. The cooperative formation of mixed micelles was obtained, and the solubility of ibuprofen in the binary mixtures was enhanced compared to the solubility in pure water and an aqueous single P407 solution. The binary mixture with the P403:P407 molar ratio of 0.75:0.25 at a total polymer concentration of 19% w/v exhibited the temperature dependence of micellization and sol-to-gel characteristics of the thermosensitive mixed micellar gels. It possessed suitable micellization and gelation characteristics for in situ gelling systems. The release of ibuprofen from the thermosensitive mixed micellar depots was sustained through a diffusion-controlled mechanism. The findings can aid in formulating binary mixtures of P403 and P407 to achieve the desired properties of mixed micelles and micellar gels. [ABSTRACT FROM AUTHOR]

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m. [ABSTRACT FROM AUTHOR]

This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol–gel transition takes place between 32–35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug. [ABSTRACT FROM AUTHOR]

The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances for drug delivery to the buccal cavity. This study aimed to prepare and characterize lipid- and surfactant-based mixed micelle in situ gel (MIG) and evaluate whether it can offer more favorable properties than the in situ gel for effective treatment of the disease. Dexamethasone was incorporated into the MIGs particles, based on Poloxamer 407 and chitosan. The lower gelation time at 37 ℃ was considered a criterion to select superior formulations among the different lipid- and surfactant-based candidates. Further characterization was performed to evaluate the opted formulations regarding morphology, physical stability, rheology, texture, and release profile. All formulations were thermoresponsive and had a shorter gelation time as the temperature increased. Dexamethasone was released in a highly controlled manner, and morphological evaluation revealed that the mixed micelle in situ gels had spherical nanoparticles. Thixotropic behavior was observed in all MIGs, indicating a prolonged retention time of the formulation after oral administration. This study has shown that among different MIGs, the one with oleic acid is a more promising candidate than the in situ gel and other MIGs for drug delivery to the buccal cavity. [ABSTRACT FROM AUTHOR]

The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment. [ABSTRACT FROM AUTHOR]

Objectives: Rebamipide, a gastroprotective drug, is used for preventing and treating ulcers but it has low aqueous solubility leading to poor bioavailability (10%). It acts both locally and systemically to provide gastroprotection and ulcer healing effects. The therapeutics of Rebamipide can be improved by enhancing its aqueous solubility and by sustaining its release in the stomach. Materials and Methods: The above objective was fulfilled by preparing solid dispersion of Rebamipide by solvent evaporation method for aqueous solubility enhancement which was incorporated in floating beads by emulsion gelation method using different concentrations of sodium alginate and olive oil for prolonged gastroretention. The beads were characterized for size, swelling, entrapment efficiency, floating lag time, floating time and in-vitro drug release. Results and Discussion: The solubility of rebamipide in solid dispersion was found to be 18.66 mg/mL which was much greater than its normal value (1.3 µg/mL). The size of beads varied between 2.03 mm-2.52 mm. The swelling index was found to be 12-28%. Entrapment efficiency was 90.1-96.9% proving excellent entrapment of drug by the method chosen. Floating lag time of optimized formulation (F6) was 3 sec with 90.2% drug release at 12 hr showing adequate sustenance of drug release. Conclusion: The solid dispersion loaded floating beads would prove effective in preventing and treating stomach ulcers because of enhanced aqueous solubility of drug in solid dispersion form resulting in higher drug concentration in gastric fluid, sustained release of drug and greater gastroretention time, giving improved therapeutics both locally and systemically. [ABSTRACT FROM AUTHOR]

The study aimed to perform a comprehensive in vitro and in vivo evaluation of a newly developed, patent-pending, powder-to-hydrogel, film-forming polymer complex base, which possesses tissue-protective and microbiome-supportive properties, and to compare its characteristics with poloxamer 407. The study used a combination of in vitro assays, including tissue viability and cell migration, and in vivo wound healing evaluations in male diabetic mice. Microbiome dynamics at wound sites were also analyzed. The in vitro assays demonstrated that the polymer complex base was non-cytotoxic and that it enhanced cell migration over poloxamer 407. In vivo, the polymer complex base demonstrated superior wound healing capabilities, particularly in combination with misoprostol and phenytoin, as evidenced by the reduced wound area and inflammation scores. Microbiome analysis revealed favorable shifts in bacterial populations associated with the polymer complex base-treated wounds. The polymer complex base demonstrates clinical significance in wound care, potentially offering improved healing, safety and microbiome support. Its transformative properties and efficacy in drug delivery make it a promising candidate for advanced wound care applications, particularly in chronic wound management. [ABSTRACT FROM AUTHOR]

The aim of this research work was to investigate the impact of various process parameters on the particle size of Febuxostat (FEB) nanocrystals using response surface methodology. The continuous microchannel nanoprecipitation technique was employed to produce FEB nanoparticles with poloxamer 407 as the polymer. Initially, a Plackett-Burman design was conducted to identify the key variables that significantly influenced the nanoprecipitation process using microfluidic techniques. The independent variables considered were solvent flow rate (X1, ml h−1), solvent-to-antisolvent ratio (X2), microchannel length (X3, cm), drug concentration (X4, mg ml−1) and polymer-to-drug ratio (X5), while the dependent variable was the particle size (Y1, nm) of the nanocrystals. Among these variables, microchannel length (X3), drug concentration (X4) and polymer-to-drug ratio (X5) showed significant influence on the particle size of nanocrystals (P < 0.001). The minimum particle size observed was 303.5 ± 2.33 nm, with a polydispersity index value of 0.159 ± 0.03, achieved at a solvent-to-antisolvent ratio of 1:2, a polymer-to-drug ratio of 1:1, a microchannel length of 50 cm and a solvent flow rate of 50 ml h−1. Subsequently, a Box-Behnken design was applied to the variables identified as significant in the Plackett-Burman design, focusing on the particle size. The results indicated that microchannel length, polymer-to-drug ratio and drug concentration had a considerable impact on the particle size of FEB. Overall, the microfluidic nanoprecipitation technique demonstrated great potential as an effective technology for reducing the size of drug crystals to the nanoscale. [ABSTRACT FROM AUTHOR]

The aim of this work was to formulate zaltoprofen (ZLT) loaded polyvinyl pyrrolidone K30 (PVP K30) nanodispersions to improve the solubility of ZLT. By varying the concentrations of PVP K30 and poloxamer 407 (1:1, 1:2, 2:1 and 2:2) different trials of ZLT nanodispersions were developed by solvent evaporation technique. The effects of formulation variables on the particle size, zeta potential, drug content, and encapsulation efficiency of ZLT loaded nanodispersions (ZLTNDs) were investigated. The average particle size, zeta potential, drug content and entrapment efficiency of ZLT nanodispersions (ZLTNDs-4) were 285.40 ± 16.41 nm, −19.06 ± 1.50 mV, 73.11 ± 0.16 mg, and 91.37 ± 0.22%, respectively. The spherical shape of the nanodispersion was verified by Transmission Electron Microscope (TEM) analysis. Further the developed formulation was characterized using Fourier Transform Infrared Spectroscopy and Differential scanning calorimetry (DSC) analysis. The in vitro release studies revealed maximum ZLT release 95.78 ± 0.85% compared to pure ZLT 36.47 ± 0.84%. The in vitro anti-inflammatory effect of pure ZLT, ZLTNDs-4 and standard drug (diclofenac sodium) was tested by protein denaturation assay, and the results exhibited superior anti-inflammatory activity of ZLTNDs-4 was 33.33 ± 1.00%). The anti- angiogenesis assay (CAM assay) results indicated that absence of vascular inhibition compared to pure ZLT. The results of the present work can be used to enhance the poorly aqueous soluble of ZLT and may be extended for other hydrophobic compounds, benefiting the pharmaceutical industries, etc. [ABSTRACT FROM AUTHOR]

Background: Theophylline (THN), a bronchodilator with potential applications in emerging conditions like COVID-19, requires a controlled-release delivery system due to its narrow therapeutic range and short half-life. This need is particularly crucial as some existing formulations demonstrate impaired functionality. This study aims to develop a new 12-h controlled-release matrix system (CRMS) in the form of a capsule to optimize dosing intervals. Methods: CRMSs were developed using varying proportions of poloxamer 407 (P-407), stearyl alcohol (STA), and hydroxypropyl methylcellulose (HPMC) through the fusion technique. Their in vitro dissolution profiles were then compared with an FDA-approved THN drug across different pH media. The candidate formulation underwent characterization using X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Additionally, a comprehensive stability study was conducted. Results: In vitro studies showed that adjusting the concentrations of excipients effectively controlled drug release. Notably, the CRMS formulation 15 (CRMS-F15), which was composed of 30% P-407, 30% STA, and 10% HPMC, closely matched the 12 h controlled-release profile of an FDA-approved drug across various pH media. Characterization techniques verified the successful dispersion of the drug within the matrix. Furthermore, CRMS-F15 maintained a consistent controlled drug release and demonstrated stability under a range of storage conditions. Conclusions: The newly developed CRMS-F15 achieved a 12 h controlled release, comparable to its FDA-approved counterpart. [ABSTRACT FROM AUTHOR]

Sodium alginate and poloxamer 407 were both studied in order to design a hydrogel-based delivery system as a platform for the formulation of vaginal medecines. Sodium alginate is a natural anionic mucoadhesive polymer while poloxamer 407 is a temperature-sensitive polymer. A commercial alginate was characterized. Then, its solutions (0.5-2 % w/w), poloxamer 407 solutions (16-21.5 % w/w) and their mixtures were prepared. Their rheological properties and the influence of vaginal simulated fluid were assessed. This commercial alginate had a mannuronate-to-guluronate ratio of 1.24, a weight-average molecular weight of 300 000 ± 2% g.mol-1, a polydispersity index of 1.8 ± 3%. Alginate solutions displayed a viscous behavior not suitable for a vaginal administration. Poloxamer solutions and their mixtures with alginate were temperature-sensitive, shear-thinning, non-thixotropic and had an elastic behavior suitable for a vaginal administration. Their resistance to dilution with vaginal fluid could prolonge vaginal residence. [ABSTRACT FROM AUTHOR]

Skin is the largest protective tissue of the body and is at risk of damage. Hence, the design and development of wound dressing materials is key for tissue repair and regeneration. Although silk fibroin is a known biopolymer in tissue engineering, its degradation rate is not correlated with wound closure rate. To address this disadvantage, we mimicked the hierarchical structure of skin and also provided antibacterial properties; a hydrogel with globular structure consisting of silk fibroin, pluronic F127, and curcumin was developed. In this regard, the effect of pluronic and curcumin on the structural and mechanical properties of the hydrogel was studied. The results showed that curcumin affected the particle size, crystallinity, and ultimate elongation of the hydrogels. In vitro assays confirmed that the hydrogel containing curcumin is not cytotoxic while the diffused curcumin and pluronic provided a considerable bactericidal property against Methicillin-resistant Staphylococcus aureus. Interestingly, presence of pluronic caused more than a 99% reduction in planktonic and adherent bacteria in the curcumin-free hydrogel groups. Moreover, curcumin improved this number further and inhibited bacteria adhesion to prevent biofilm formation. Overall, the developed hydrogel showed the potential to be used for skin tissue regeneration.

This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol–gel transition takes place between 32–35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug.

The aqueous solution of binary mixtures of amphiphilic copolymers is a potential platform for fabricating mixed polymeric micelles for pharmaceutical applications, particularly in developing drug delivery depots for a poorly water-soluble compound. This study fabricated and investigated binary mixtures of poloxamer 403 (P403) and poloxamer 407 (P407) at varying P403:P407 molar ratios to develop a vehicle for the poorly water-soluble compound, using ibuprofen as a model drug. The cooperative formation of mixed micelles was obtained, and the solubility of ibuprofen in the binary mixtures was enhanced compared to the solubility in pure water and an aqueous single P407 solution. The binary mixture with the P403:P407 molar ratio of 0.75:0.25 at a total polymer concentration of 19% w/v exhibited the temperature dependence of micellization and sol-to-gel characteristics of the thermosensitive mixed micellar gels. It possessed suitable micellization and gelation characteristics for in situ gelling systems. The release of ibuprofen from the thermosensitive mixed micellar depots was sustained through a diffusion-controlled mechanism. The findings can aid in formulating binary mixtures of P403 and P407 to achieve the desired properties of mixed micelles and micellar gels.

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson's disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson's disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson's disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing. [ABSTRACT FROM AUTHOR]

Sodium alginate and poloxamer 407 were both studied in order to design a hydrogel-based delivery system as a platform for the formulation of vaginal medecines. Sodium alginate is a natural anionic mucoadhesive polymer while poloxamer 407 is a temperature-sensitive polymer. A commercial alginate was characterized. Then, its solutions (0.5-2 % w/w), poloxamer 407 solutions (16-21.5 % w/w) and their mixtures were prepared. Their rheological properties and the influence of vaginal simulated fluid were assessed. This commercial alginate had a mannuronate-to-guluronate ratio of 1.24, a weight-average molecular weight of 300 000 ± 2% g.mol-1, a polydispersity index of 1.8 ± 3%. Alginate solutions displayed a viscous behavior not suitable for a vaginal administration. Poloxamer solutions and their mixtures with alginate were temperature-sensitive, shear-thinning, non-thixotropic and had an elastic behavior suitable for a vaginal administration. Their resistance to dilution with vaginal fluid could prolonge vaginal residence. [ABSTRACT FROM AUTHOR]

The present work aims to develop mucoadhesive thermosensitive nasal in situ gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal mucociliary clearance (MCC) and increase residence of the drug on nasal mucosa. This might increase drug absorption to improve bioavailability of the drug as compared to oral dosage form. Promethazine hydrochloride is an antiemetic drug administered by oral, parenteral and rectal routes. These routes have poor patient compliance or low bioavailability. Nasal route is a better alternative as it has large surface area, high drug absorption rate and no first pass effect. Its only limitation is short drug retention time due to MCC. By formulating a mucoadhesive in situ gel, the MCC can be reduced, and drug absorption will be prolonged. Thus, improving bioavailability. In-situ gel was prepared by cold method having material attributes as concentration of Poloxamer 407 (X1) as gelling agent and hydroxypropyl methyl cellulose K4M (X2) as mucoadhesive agent. Critical Quality Attributes (CQA) were gelation temperature, mucoadhesive force and ex-vivo diffusion. Central composite design (CCD) was adopted for optimization. Optimized formulation satisfied all the CQA significant for nasal administration. Moreover, the formulation was found to be stable in accelerated stability studies for 3 months. It can be concluded that since the drug can easily permeate through nasal mucosa and can gain access directly in the brain without undergoing first pass metabolism along with increased residence due to mucoadhesion, mucoadhesive in situ gel has potential to increase drug bioavailability. [ABSTRACT FROM AUTHOR]

Calcium phosphate cement (CPC) is generally used for bone repair and augmentation. Poloxamers are tri‐block copolymers that are used as surfactants but have applications in drug and antibiotic delivery. However, their biological effects on bone regeneration systems remain unelucidated. Here, we aimed to understand how supplementing the prototype CPC with poloxamer would impact cellular activity and its function as a bone‐grafting material. A novel CPC, modified beta‐tricalcium phosphate (mβ‐TCP) powder, was developed through a planetary ball‐milling process using a beta‐tricalcium phosphate (β‐TCP). The mβ‐TCP dissolves rapidly and accelerates hydroxyapatite precipitation; successfully shortening the cement setting time and enhancing the strength. Furthermore, the addition of poloxamer 407 to mβ‐TCP could reduce the risk of leakage from bone defects and improve fracture toughness while maintaining mechanical properties. In this study, the poloxamer addition effects (0.05 and 0.1 g/mL) on the cellular activities of MC3T3‐E1 cells cultured in vitro were investigated. The cell viability of mβ‐TCP containing poloxamer 407 was similar to that of mβ‐TCP. All specimens showed effective cell attachment and healthy polygonal extension of the cytoplasm firmly attached to hydroxyapatite (HA) crystals. Therefore, even with the addition of poloxamer to mβ‐TCP, it does not have a negative effect to osteoblast growth. These data demonstrated that the addition of poloxamer 407 to mβ‐TCP might be considered a potential therapeutic application for the repair and regeneration of bone defects. [ABSTRACT FROM AUTHOR]

Traditional eye drops used for topically administering drugs have poor ocular bioavailability due to the biological barriers of the eye. There is an interest to design and develop novel drug delivery systems that would extend the precorneal residence time, reduce the frequency of administration and decrease dose-related toxicity. This study aimed to prepare Nanoparticles of Gemifloxacin Mesylate and incorporate them into an in situ gel. The nanoparticles were prepared by ionic gelation technique, using 32 factorial design. Sodium tripolyphosphate (STPP) was used to crosslink Chitosan. The optimized formulation of the nanoparticles (GF4) contained 0.15% Gemifloxacin Mesylate, 0.15% Chitosan and 0.20% STPP, producing 71 nm particle size and 81.11% entrapment efficiency. The prepared nanoparticles showed biphasic release, with an initial burst release of 15% in 1.0 hr and a cumulative drug release of 90.53% at the end of 24 hrs. After that, the prepared nanoparticles were incorporated into an in situ gel, using Poloxamer 407, producing a sustained drug release with efficient antimicrobial activity against gram-positive and gram-negative bacteria as confirmed by the cup plate method. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop poloxamer (P407)-based in-situ thermogellable hydrogels with reducing concentration of P407 by adding hypromellose (HPMC) and with enhancing mucoadhesion of resulting hydrogels by adding hyaluronic acid (HA) for prolonging ocular delivery of hydroxypropyl-β-cyclodextrin (HPβCD)-solubilized testosterone (TES). Results demonstrated that 0.5% TES solution was successfully solubilized with adding 10% HPβCD. Non-gellable 13% P407 sol became in-situ gellable with adding 2.0-2.5% HPMC and mucoadhesibility was further imporved with adding 0.3% HA-L (low MW) or HA-H (high MW). Optimized 0.5% HPβCD-solubilized TES P407-based thermogellable hydrogels with enhancement of mucoadhesion for prolonging ocular delivery comprised 13% P407, 2.5% HPMC, and 0.3% HA-L or HA-H. Furthermore, rheological measurements under simulated eye blinking confirmed that non-thixotropic properties of optimized hydrogels could be spreaded evenly and retain a greater amount of drug-loaded hydrogels on the ocular surface for a longer period to prolong drug delivery. Compared with conventional eye drops, the prolonged residence time of optimized hydrogels from ex vivo and in vivo studies were observed, indicating relationships between rheological properties and in vivo performances. It was concluded that P407-based thermosensitive hydrogels with reducing concentration of P407 and enhancing mucoadhesion was successfully formulated by adding 2.5% HPMC and 0.3% HA in 13% P407 for potentially accomplishing effective clinical treatment of DED. [ABSTRACT FROM AUTHOR]

Purpose: The current investigative study was performed to analyze and compare the effect of gellan gum-mixed poloxamer 407 as compared to plain poloxamer 407 on the in situ gelling behavior as well as drug release of the best formulation. Method: Azelastine hydrochloride-loaded poloxamer 407 micelles and poloxamer 407 gellan gum micelles were prepared with the help of thin film hydration followed by the characterization of the micelles by evaluating the particle size, entrapment efficiency, pH, and gelation as well as in vitro and in vivo drug release analysis. Result: The azelastine hydrochloride poloxamer 407 with gellan gum micelles having a particle size below 100 nm were found to show low gelation temperature which further increases the retention time of the formulation at the site of administration and results in a controlled release formulation. The in vitro drug release showed significant release of 85% and 89% of drug in the 10th hour while the in vivo analysis showed similar effect as that of the marketed formulation of AzelastTM. Conclusion: A controlled release in situ temperature sensitive gel was successfully formulated which showed significant effect to reduce allergic conjunctivitis. [ABSTRACT FROM AUTHOR]

This manuscript explains the effect of biologically important additives on the micellar behavior of an ethylene oxide‐propylene oxide (PEO101‐PPO56‐PEO101) based linear block copolymer, Poloxamer 407.The effect of common pharmaceutical excipients and three vital amino acids viz. alanine, glycine, and lysine (Ala, Gly, and Lys) is examined with the help of cloud point (CP), dynamic light scattering (DLS), and small angle neutron scattering (SANS) techniques. The drug solubilization ability for the copolymer was checked for two model drugs Quercetin (QCT) and Ibuprofen (IBU) with the help of high‐performance liquid chromatography (HPLC) in the presence/absence of additives such as Ala, Gly, and Lys. The observed results reveal that higher amino acid concentrations, favor the solubilization of drug which can potentially benefit the use of these biocompatible copolymers in pharmaceutical and biopharma industries. [ABSTRACT FROM AUTHOR]

Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 μg of MF/g of tissue vs. <10 μg of MF/g of tissue, respectively). [Display omitted] • Mometasone Furoate (MF), a lipophilic steroidal drug, is widely used to treat sinus related diseases. • The marketed MF aqueous suspension formulations contain crystalline MF and suffers from fast clearance from the nasal cavity. • Thermoresponsive hydrogels (HG) can enable extended sinus residence but loading of lipophilic MF in aqueous HG is challenging. • Composite HG with porous silicon (pSi)-based carriers can enable incorporation of lipophilic MF in aqueous HG. • MF loaded pSi embedded HG are non-toxic to human nasal tissue and significantly increase drug uptake into nasal tissue. [ABSTRACT FROM AUTHOR]

Infectious diseases caused by pathogenic microorganisms pose significant threats to public health globally. The emergence of antibiotic-resistant bacteria has further complicated the treatment of these infections, necessitating the exploration of alternative therapeutic strategies. Among these strategies, the use of hydrogels as delivery systems for delivering antimicrobial agents has gained considerable attention. This paper presents a comprehensive bibliometric analysis of the utilization of Pluronic F-127 (PF-127) hydrogel for delivering antimicrobial agents. The aim of this study is to explore the current research landscape, identify key trends, influential authors, and prominent journals in this field. The analysis is based on a systematic search conducted using the Scopus database. The analysis covered publication trends, geographic distribution, influential authors, and key journals in the field of PF-127 hydrogel-based antimicrobial agent delivery. The results revealed the growing interest in this field, with a focus on countries such as India, the United States, and Egypt. The analysis also identified top authors, institutions, and journals contributing to the research. The findings reveal the growth of research in this area, highlighting the potential of PF-127 hydrogel as a promising vehicle for antimicrobial agent delivery. It highlights the need for further research to optimize formulation parameters, explore combination therapies, conduct in vivo studies, and promote collaboration to maximize the therapeutic potential of PF-127 hydrogel-based delivery systems in combating infectious diseases and antimicrobial resistance. This paper provides valuable insights into the existing literature and serves as a reference for future research and development in the field.

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.

The study aimed to perform a comprehensive in vitro and in vivo evaluation of a newly developed, patent-pending, powder-to-hydrogel, film-forming polymer complex base, which possesses tissue-protective and microbiome-supportive properties, and to compare its characteristics with poloxamer 407. The study used a combination of in vitro assays, including tissue viability and cell migration, and in vivo wound healing evaluations in male diabetic mice. Microbiome dynamics at wound sites were also analyzed. The in vitro assays demonstrated that the polymer complex base was non-cytotoxic and that it enhanced cell migration over poloxamer 407. In vivo, the polymer complex base demonstrated superior wound healing capabilities, particularly in combination with misoprostol and phenytoin, as evidenced by the reduced wound area and inflammation scores. Microbiome analysis revealed favorable shifts in bacterial populations associated with the polymer complex base-treated wounds. The polymer complex base demonstrates clinical significance in wound care, potentially offering improved healing, safety and microbiome support. Its transformative properties and efficacy in drug delivery make it a promising candidate for advanced wound care applications, particularly in chronic wound management.

The design and development of pharmaceutical products require specific knowledge, time, and investment. Response surface methodology (RSM) is a widely used technique in the design of experiments (DoE) to optimize various processes and products. The aim of this study was to model and produce experimental emulgels containing 1% ciclopirox olamine and to evaluate their physical, rheological, and mechanical properties and their ability to release ciclopirox olamine. The objective was to optimize the composition of the experimental emulgel containing 1% ciclopirox olamine by applying a central composite design based on selected criteria. The surfactant (polysorbate 80) had the greatest influence on the physical, rheological, and mechanical properties of the emulgels, as well as on the release of ciclopirox olamine from these systems. During the optimization process, an emulgel of optimal composition was generated containing 38.27% mineral oil, 6.56% polysorbate 80, and 55.17% hydrogel containing 1% ciclopirox olamine, meeting specified criteria (dependent variables) including the maximum flux of ciclopirox olamine, the minimum sol–gel transition temperature (Tsol/gel), and the minimum particle size of the oil phase. The oil phase particle size (D50) of this emulgel was determined to be 0.337 µm, the system Tsol/gel was 9.1 °C, and the flux of ciclopirox olamine from this gel matrix was calculated to be 1.44 mg/cm2. This emulgel of optimal composition could be used to treat fungal skin diseases.

Pluronic F-127 (PF-127) hydrogel is a versatile biomaterial with promising applications in drug delivery, tissue engineering, and regenerative medicine. PF-127 has antiadhesive activity that prevents bacterial adhesion by creating a hydrated layer on the bacterial surface. This property makes PF-127 suitable for preventing implant-associated infections. In this study, we aimed to evaluate the antibacterial properties of PF-127 using field isolates of Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria) and compare them with different antibiotic standards. The antimicrobial potential was assessed using disk diffusion assays with four standard concentrations (20%, 25%, 30%, and 40%). The test microorganisms were inoculated on agar plates, and sterile filter paper disks infused with PF-127 hydrogels were placed alongside standard antibiotic disks. After incubation, the inhibition zones were measured to determine antimicrobial activity. Our results showed that PF-127 lacked intrinsic antimicrobial activity against S. aureus and E. coli at the tested concentrations. In conclusion, PF-127 hydrogel is a promising neutral carrier hydrogel system for loading antibiotics and antimicrobial compounds. Its unique properties, such as biocompatibility and thermo-responsive behaviour, combined with its antiadhesive activity, make it an ideal candidate for various biomedical applications.

AbstractTraditional eye drops used for topically administering drugs have poor ocular bioavailability due to the biological barriers of the eye. There is an interest to design and develop novel drug delivery systems that would extend the precorneal residence time, reduce the frequency of administration and decrease dose-related toxicity. This study aimed to prepare Nanoparticles of Gemifloxacin Mesylate and incorporate them into an in situ gel. The nanoparticles were prepared by ionic gelation technique, using 32 factorial design. Sodium tripolyphosphate (STPP) was used to crosslink Chitosan. The optimized formulation of the nanoparticles (GF4) contained 0.15% Gemifloxacin Mesylate, 0.15% Chitosan and 0.20% STPP, producing 71 nm particle size and 81.11% entrapment efficiency. The prepared nanoparticles showed biphasic release, with an initial burst release of 15% in 1.0 hr and a cumulative drug release of 90.53% at the end of 24 hrs. After that, the prepared nanoparticles were incorporated into an in situ gel, using Poloxamer 407, producing a sustained drug release with efficient antimicrobial activity against gram-positive and gram-negative bacteria as confirmed by the cup plate method.

AbstractThe purpose of this study was to develop poloxamer (P407)-based in-situ thermogellable hydrogels with reducing concentration of P407 by adding hypromellose (HPMC) and with enhancing mucoadhesion of resulting hydrogels by adding hyaluronic acid (HA) for prolonging ocular delivery of hydroxypropyl-β-cyclodextrin (HPβCD)-solubilized testosterone (TES). Results demonstrated that 0.5% TES solution was successfully solubilized with adding 10% HPβCD. Non-gellable 13% P407 sol became in-situ gellable with adding 2.0-2.5% HPMC and mucoadhesibility was further imporved with adding 0.3% HA-L (low MW) or HA-H (high MW). Optimized 0.5% HPβCD-solubilized TES P407-based thermogellable hydrogels with enhancement of mucoadhesion for prolonging ocular delivery comprised 13% P407, 2.5% HPMC, and 0.3% HA-L or HA-H. Furthermore, rheological measurements under simulated eye blinking confirmed that non-thixotropic properties of optimized hydrogels could be spreaded evenly and retain a greater amount of drug-loaded hydrogels on the ocular surface for a longer period to prolong drug delivery. Compared with conventional eye drops, the prolonged residence time of optimized hydrogels from ex vivo and in vivo studies were observed, indicating relationships between rheological properties and in vivo performances. It was concluded that P407-based thermosensitive hydrogels with reducing concentration of P407 and enhancing mucoadhesion was successfully formulated by adding 2.5% HPMC and 0.3% HA in 13% P407 for potentially accomplishing effective clinical treatment of DED.

Objective: This research aimedto evaluate the effects of chitosan and poloxamer 407 on in vitro cytotoxicity, anti-inflammatory, wound healing, and antimicrobial activities of 0.3% w/v benzydamine hydrochloride (HCl) oromucosal solutions. Material and Methods: The effects of three alcohol-free benzydamine HCl oromucosal formulations; containing: 1) 0.5% w/v chitosan, 2) 15% w/v poloxamer 407, and 3) a combination of 0.5% w/v chitosan and 15% w/v poloxamer 407, on in vitro cytotoxicity and biological activities were evaluated and compared to a commercial benzydamine HCl mouth spray, containing alcohol and 0.12% chlorhexidine solution. Results: All alcohol-free benzydamine HCl formulations and their vehicles were less cytotoxic to the macrophage RAW 264.7 cell line than the commercial spray and to the human gingival fibroblast cell line than chlorhexidine, respectively. The formulation containing 0.5% w/v chitosan exhibited the highest wound healing activity on the fibroblast cells among all tested products, and showed anti-inflammatory activity on macrophage cells, which is comparable to benzydamine HCl. Furthermore, from the time-kill assay, this formulation completely inhibited Streptococcus mutans within 1 minute, similar to 0.12% chlorhexidine solution, and reduced the cell number of Candida albicans more rapidly than the commercial spray. Conclusion: The alcohol-free benzydamine HCl solution containing 0.5% w/v chitosan as a mucoadhesive polymer is a promising oral care candidate, which is safe to be used, and has wound healing, anti-inflammatory, and antimicrobial activities.

The reason for conducting this study is to prolong release of miconazole in the ocular site of action by ocular-based gels (OBGs) formulations. The formulation factors affecting on the release from OBG should be studied using various gelling agents in various concentrations to achieve the improvement in retention and residence time in response to prolonged release. In this study, the formulations were prepared using carbopol 940, pectin, sodium alginate, poloxamer 407, and poly(methacrylic acid) at 0.5%, 1%, and 1.5% w/v, respectively. Hydroxypropyl methylcellulose E5 (HPMC E5) 1% was added as thickening agent/viscosity builder. The formulation containing carbopol 940, pectin and sodium alginate at 1.5% w/v, displayed a noticable improvement in viscosity, gelling capacity, and extended release for 7 h in comparison with the reference drug. Overall, the release showed that the sodium alginate with HPMC E5 form in situ gel which had longer time of release reach to 12 h compared with other polymers. the release of miconazole from the OBGs affected significantly by two factors includes gelling capacity and viscosity builder. The novelty of this study is supporting the delivery of ocular drugs through a cornea as an important key of the eye instead of dependence on an internal blood supply using an oral or a parental administration. [ABSTRACT FROM AUTHOR]

The present study aimed to prepare, characterize, and evaluate a thermo-responsive sol–gel for intranasal delivery of lamotrigine (LTG), which was designed for sustained drug delivery to treat epilepsy. LTG sol–gel was prepared using the cold method by changing the concentrations of poloxamer 407 and poloxamer 188, which were used as thermo-reversible polymers. The optimized formulations of sol–gel were analyzed for clarity, pH, viscosity, gelation temperature, gelation time, spreadability, drug content, in vitro drug release studies, ex vivo permeation studies, and in vivo toxicological studies. FTIR, XRD, and DSC were performed to determine the thermal stability of the drug and polymers. The prepared formulations had a clear appearance in sol form; they were liquid at room temperature and became gel at temperatures between 31 °C and 36 °C. The pH was within the range of the nasal pH, between 6.2 and 6.4. The drug content was found to be between 92% and 94%. In vitro drug release studies indicated that the formulations released up to 92% of the drug within 24 h. The FTIR, DSC, and XRD analyses showed no interaction between the drug and the polymer. A short-term stability study indicated that the formulation was stable at room temperature and at 4–8 °C. There was a slight increase in viscosity at room temperature, which may be due to the evaporation of the vehicle. A histological study indicated that there were no signs of toxicity seen in vital organs, such as the brain, kidney, liver, heart, and spleen. It can be concluded from the above results that the prepared intranasal sol–gel for the delivery of LTG is safe for direct nose-to-brain delivery to overcome the first-pass effect and thus enhance bioavailability. It can be considered an effective alternative to conventional drug delivery for the treatment of epilepsy. [ABSTRACT FROM AUTHOR]

[Display omitted] Deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are bile acids that may serve as permeation enhancers when incorporated within the nanogel matrix for drug delivery in the inner ear. In this study, thermoresponsive nanogels were formulated with DCA, LCA and UDCA and their rheological properties and biocompatibility were assessed. The impact of nanogel on cellular viability was evaluated via cell viability assay, the impact of nanogels on cellular bioenergetic parameters was estimated by Seahorse mito-stress test and glycolysis-stress test, while the presence of intracellular free radicals was assessed by reactive oxygen species assay. Nanogels showed a high level of biocompatibility after 24-hour exposure to auditory and macrophage cell lines, with minimal cytotoxicity compared to untreated control. Incubation with nanogels did not alter cellular respiration and glycolysis of the auditory cell line but showed possible mitochondrial dysfunction in macrophages, suggesting tissue-dependent effects of bile acids. Bile acid-nanogels had minimal impact on intracellular reactive oxygen species, with LCA demonstrating the most pro-oxidative behaviour. This study suggests that thermoresponsive nanogels with bile acid, particularly DCA and UDCA, may be promising candidates for inner ear drug delivery. [ABSTRACT FROM AUTHOR]

Tofacitinib, an inhibitor of Janus kinases (JAKs) 1 and 3, has been shown to be effective in the treatment of rheumatoid arthritis. The incidence of hyperlipidemia has been found to be higher in patients with rheumatoid arthritis. The present study therefore investigated the pharmacokinetics of tofacitinib after its intravenous (10 mg/kg) or oral (20 mg/kg) administration in poloxamer-407-induced hyperlipidemic (PHL) rats. The area under the plasma concentration-time curve from zero to infinity (AUC0–∞) after intravenous administration of tofacitinib was 73.5% higher in PHL than in control rats, owing to slower time-averaged nonrenal clearance (CLNR) in the former. Evaluation of in vitro metabolism showed that the intrinsic clearance (CLint) of tofacitinib was 38.6% lower in PHL than in control rats, owing to the decreased protein expression of hepatic cytochrome P450 (CYP) 3A1/2 and CYP2C11 in PHL rats. Similar results were observed in PHL rats after oral administration of tofacitinib. These results were likely due to the decreased CLNR, CLint, and P-glycoprotein (P-gp) expression in the intestines of PHL compared to control rats. Overall, these findings indicated that hyperlipidemia slowed the metabolism of tofacitinib, increasing its plasma concentrations, and that this reduced metabolism was due to alterations in expression of the proteins CYP3A1/2, CYP2C11, and P-gp in the liver and/or intestines of PHL rats. [ABSTRACT FROM AUTHOR]

Infectious diseases caused by pathogenic microorganisms pose significant threats to public health globally. The emergence of antibiotic-resistant bacteria has further complicated the treatment of these infections, necessitating the exploration of alternative therapeutic strategies. Among these strategies, the use of hydrogels as delivery systems for delivering antimicrobial agents has gained considerable attention. This paper presents a comprehensive bibliometric analysis of the utilization of Pluronic F-127 (PF-127) hydrogel for delivering antimicrobial agents. The aim of this study is to explore the current research landscape, identify key trends, influential authors, and prominent journals in this field. The analysis is based on a systematic search conducted using the Scopus database. The analysis covered publication trends, geographic distribution, influential authors, and key journals in the field of PF-127 hydrogel-based antimicrobial agent delivery. The results revealed the growing interest in this field, with a focus on countries such as India, the United States, and Egypt. The analysis also identified top authors, institutions, and journals contributing to the research. The findings reveal the growth of research in this area, highlighting the potential of PF-127 hydrogel as a promising vehicle for antimicrobial agent delivery. It highlights the need for further research to optimize formulation parameters, explore combination therapies, conduct in vivo studies, and promote collaboration to maximize the therapeutic potential of PF-127 hydrogel-based delivery systems in combating infectious diseases and antimicrobial resistance. This paper provides valuable insights into the existing literature and serves as a reference for future research and development in the field. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to develop niosomes using polyoxyethylene lauryl ether (Brij-35) and poloxamer 407 surfactants for dissolution enhancement of tacrolimus, a poorly water-soluble drug for improving oral bioavailability. Methods: Niosomes were prepared using surfactants polyoxyethylene lauryl ether (Brij-35) (Group I), poloxamer 407 (Group II), and hybrid niosomes including both Brij-35 and poloxamer 407 (Group III). A thin film hydration technique was employed for the development of niosomes. Drug-surfactant interactions were examined using FTIR. The entrapment efficiency of niosomes was determined using ultra-centrifugation technique. Vesicle size, PDI, and zeta potential were measured by DLS experiments. Morphological evaluation of vesicles was carried out using SEM microscopy. DSC technique was used to evaluate the thermal behavior of niosomes. In vitro dissolution study of optimized niosomes (F1-Br35, F1-PL407, and F1-BrPL) was performed by dialysis bag method. Results: FTIR studies revealed the compatibility of tacrolimus with used surfactants. Percent entrapment efficiency values were in the range of 88.65 ± 3.13 to 93.67 ± 1.57% for Brij-35-based formulations, 87.83 ± 6.24 to 89.01 ± 5.83% for poloxamer 407, and 90.08 ± 1.12 to 92.81 ± 0.31% for hybrid niosomes. The vesicle size of niosomes was in the range of 282.5 to 622.5 nm. SEM analysis showed an almost spherical shape of optimized formulations (F1-Br35, F1-PL407, and F1-BrPL). DSC analysis demonstrated amorphous form of tacrolimus indicating improved dissolution of tacrolimus. In vitro dissolution of optimized formulations F1-Br35, F1-PL407, and F1-BrPL at pH 7.4 indicated an improved dissolution profile of tacrolimus compared to pure drug aqueous dispersion. Conclusion: Overall, the results of the study concluded that newly developed niosomes could act as a promising approach for enhancing the dissolution profile of tacrolimus and can act as alternate oral carriers. [ABSTRACT FROM AUTHOR]

Background: Theophylline (THN), a bronchodilator with potential applications in emerging conditions like COVID-19, requires a controlled-release delivery system due to its narrow therapeutic range and short half-life. This need is particularly crucial as some existing formulations demonstrate impaired functionality. This study aims to develop a new 12-h controlled-release matrix system (CRMS) in the form of a capsule to optimize dosing intervals. Methods: CRMSs were developed using varying proportions of poloxamer 407 (P-407), stearyl alcohol (STA), and hydroxypropyl methylcellulose (HPMC) through the fusion technique. Their in vitro dissolution profiles were then compared with an FDA-approved THN drug across different pH media. The candidate formulation underwent characterization using X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Additionally, a comprehensive stability study was conducted. Results: In vitro studies showed that adjusting the concentrations of excipients effectively controlled drug release. Notably, the CRMS formulation 15 (CRMS-F15), which was composed of 30% P-407, 30% STA, and 10% HPMC, closely matched the 12 h controlled-release profile of an FDA-approved drug across various pH media. Characterization techniques verified the successful dispersion of the drug within the matrix. Furthermore, CRMS-F15 maintained a consistent controlled drug release and demonstrated stability under a range of storage conditions. Conclusions: The newly developed CRMS-F15 achieved a 12 h controlled release, comparable to its FDA-approved counterpart.

Avascular necrosis (AVN) involves ischemic cell death of the bone. AVN leaves an abundance of necrotic lipids and debris in the bone marrow, which instigates inflammatory bone repair. Consequently, the necrotic bone microenvironment stimulates excessive bone resorption, leading to joint deformities and osteoarthritis. Here, we performed a detergent‐assisted bone wash using poloxamer 407 (P407) to clean the necrotic bone environment by removing lipids and necrotic debris. The new concept was tested using an established ex vivo AVN model of porcine cadaver humeral heads. The P407 wash was performed using P407 solution and followed with saline via two intraosseous needles. Visual inspection and image analyses of average pixel light intensity showed that the P407 wash produced a better‐cleaned bone than the saline wash. Analyses of the collected bone wash solution showed a two‐fold increase in triglycerides (101 vs. 53 mmol/head, p = 0.006) and a 10‐fold increase in the dry weight of the removed debris (1.34 vs. 0.13 g/head, p = 0.02) with the P407 wash compared to saline. The histological evaluation showed significantly decreased Oil‐Red‐O (fats) staining in the P407‐washed bone compared with the saline‐washed bone. The in vitro assays of Alizarin red and qPCR showed the P407 wash neither altered the osteogenic behaviors of porcine bone marrow‐derived mesenchymal cells (pBMMCs) nor raised inflammatory responses of porcine bone marrow‐derived macrophages (pBMMs). In conclusion, detergent‐assisted bone wash using P407 produced a better removal of nonsoluble debris from the bone marrow space than the saline wash without causing changes to osteogenesis or inflammatory reactions. [ABSTRACT FROM AUTHOR]

Hydrogel-based wound dressings hold a unique position in comparison to conventional dressings, owing to their extensive potential as wound and burn healing scaffolds. Moxifloxacin, a synthetic fluoroquinolone, was granted approval by the FDA in 1999 for intravenous administration in the treatment of complex and severe bacterial infections, such as challenging skin and intraabdominal infections. Lidocaine is a widely recognised local anaesthetic that has been extensively utilised in medical practise for the management of acute wound pain, either as a standalone treatment or in combination with other anaesthetic drugs. A total of eighteen hydrogel formulations were developed by using a mixture of moxifloxacin and lidocaine, utilising different proportions of carbapol 940, poloxamer 407, carboxymethyle sodium, and chitosan polymers. These formulations were assigned unique codes ranging from F1 to F18. The hydrogel formulations (F1-F9) are composed of carbapol 940 as the base polymer, with polymer ratios ranging from 1-2% W/V. On the other hand, formulations (F10-F12) consist of poloxamer 407 as the base polymer, with polymer ratios of 20, 25, and 30% W/V, respectively. Additionally, formulations (F13-F15) are based on sodium carboxymethyl cellulose, with polymer ratios of 3, 6, and 10% W/V, respectively. Lastly, formulations (F16-F18) are chitosan-based, with polymer ratios of 2, 4, and 6% W/V, respectively. The formulated compounds were examined for their sensory, physical, chemical, and mechanical characteristics. The present study aimed to investigate the influence of polymer type and concentration on the in vitro release behaviour. Among the tested polymers, F4 exhibited favourable characteristics in terms of release profile and swelling capacity. Based on these findings, it can be inferred that the incorporation of moxifloxacin and lidocaine base into a hydrogel composed of 1.5% carbopol 940 with 0.5% triethanolamine enables sustained release and adequate swelling, making it suitable for the management of burn or wound conditions. Further investigations, such as histological and in vivo studies, could be conducted in the future to evaluate the selected formulation. [ABSTRACT FROM AUTHOR]

The combination of the thermoresponsive polymer and protein has demonstrated great promise in its applications in drug delivery and tissue engineering fields. This study described the impact of bovine serum albumin (BSA) on the micellization and sol–gel transition behaviors of poloxamer 407 (PX). The micellization of aqueous PX solutions with and without BSA was examined using isothermal titration calorimetry. In the calorimetric titration curves, the pre-micellar region, the transition concentration region, and the post-micellar region were observed. The presence of BSA had no noticeable impact on critical micellization concentration, but the inclusion of BSA caused the pre-micellar region to expand. In addition to studying the self-organization of PX at a particular temperature, the temperature-induced micellization and gelation of PX were also explored using differential scanning calorimetry and rheology. The incorporation of BSA had no discernible effect on critical micellization temperature (CMT), but it did affect gelation temperature (Tgel) and gel integrity of PX-based systems. The response surface approach illustrated the linear relation between the compositions and the CMT. The major factor affecting the CMT of the mixtures was the concentration of PX. The alteration of the Tgel and the gel integrity were discovered to be a consequence of the intricate interaction between PX and BSA. BSA mitigated the inter-micellar entanglements. Hence, the addition of BSA demonstrated a modulating influence on Tgel and a softening effect on gel integrity. Understanding the influence of serum albumin on the self-assembly and gelation of PX will enable the creation of thermoresponsive drug delivery and tissue engineering systems with controlled gelation temperatures and gel strength. [ABSTRACT FROM AUTHOR]

Pluronic F-127 (PF-127) hydrogel is a versatile biomaterial with promising applications in drug delivery, tissue engineering, and regenerative medicine. PF-127 has antiadhesive activity that prevents bacterial adhesion by creating a hydrated layer on the bacterial surface. This property makes PF-127 suitable for preventing implant-associated infections. In this study, we aimed to evaluate the antibacterial properties of PF-127 using field isolates of Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria) and compare them with different antibiotic standards. The antimicrobial potential was assessed using disk diffusion assays with four standard concentrations (20%, 25%, 30%, and 40%). The test microorganisms were inoculated on agar plates, and sterile filter paper disks infused with PF-127 hydrogels were placed alongside standard antibiotic disks. After incubation, the inhibition zones were measured to determine antimicrobial activity. Our results showed that PF-127 lacked intrinsic antimicrobial activity against S. aureus and E. coli at the tested concentrations. In conclusion, PF-127 hydrogel is a promising neutral carrier hydrogel system for loading antibiotics and antimicrobial compounds. Its unique properties, such as biocompatibility and thermo-responsive behaviour, combined with its antiadhesive activity, make it an ideal candidate for various biomedical applications. [ABSTRACT FROM AUTHOR]