Search Results (198)

Traditional wound and burn treatments often fall short in balancing antimicrobial efficacy, patient comfort, and ease of application. This study introduces a novel, transparent, thermoresponsive sol–gel formulation incorporating polyhexamethylene biguanide (PHMB) for advanced topical therapy. Utilizing Poloxamer 407 as a biocompatible carrier, the formulation remains a sprayable liquid at room temperature and instantly gels upon contact with body temperature, enabling painless, pressure-free application on sensitive, injured skin. Comprehensive in vitro and in vivo evaluations confirmed the formulation’s broad-spectrum antimicrobial efficacy (≥5 log₁₀ reduction in 30 s), high biocompatibility (viability > 70% in fibroblasts), non-irritancy (OECD 425-compliant), and physical stability across three months. Importantly, the formulation maintained fibroblast migration capacity—crucial for wound regeneration—while exhibiting rapid sol-to-gel transition at ~34 °C. These findings highlight the system’s potential as a next-generation wound dressing with enhanced user compliance, transparent monitoring capability, and rapid healing support, particularly in disaster or emergency scenarios. Full article

Background/Objectives: Non-invasive central nervous system (CNS) therapies are limited by complex mechanisms and the blood–brain barrier, but nasal delivery offers a promising alternative. The study planned to develop a non-invasive in situ intranasal mucoadhesive thermosensitive gel to deliver CNS-active risperidone via nose-to-brain targeting. Risperidone, a second-generation antipsychotic, has shown efficacy in managing both psychotic and mood-related symptoms. The mucoadhesive gel formulations help to prolong the residence time at the nasal absorption site, thereby facilitating the uptake of the drug. Methods: The poloxamer 407 (18.0% w/v), HPMC K100M and K15M (0.3–0.5% w/v), and benzalkonium chloride (0.1% v/v) were used as thermosensitive polymers, a mucoadhesive agent, and a preservative, respectively, for the development of in situ thermosensitive gel. The developed formulations were evaluated for various parameters. Results: The pH, gelation temperature, gelation time, and drug content were found to be 6.20 ± 0.026–6.37 ± 0.015, 34.25 ± 1.10–37.50 ± 1.05 °C, 1.65 ± 0.30–2.50 ± 0.55 min, and 95.58 ± 2.37–98.03 ± 1.68%, respectively. Furthermore, the optimized F3 formulation showed satisfactory gelling capacity (9.52 ± 0.513 h) and an acceptable mucoadhesive strength (1110.65 ± 6.87 dyne/cm²). Diffusion of the drug through the egg membrane depended on the formulation’s viscosity, and the F3 formulation explained the first-order release kinetics, indicating concentration-dependent drug diffusion with n < 0.45 (0.398) value, indicating the Fickian-diffusion (diffusional case I). The pharmacokinetic study was performed with male Wistar albino rats, and the F3 in situ thermosensitive risperidone gel confirmed significantly (p < 0.05) ~5.4 times higher brain AUC_0–∞ when administered intranasally compared to the oral solution. Conclusions: Based on physicochemical, in vitro, and in vivo parameters, it can be concluded that in situ thermosensitive gel is suitable for administration of risperidone through the nasal route and can enhance patient compliance through ease of application and with less repeated administration. Full article

pH-sensitive hydrogels are important soft biomaterials as they mimic biological organisms by altering their properties in response to small pH changes in biological fluids. In this work, novel chitosan (Cs) hydrogels were developed using an innovative dual curcumin (Cur) encapsulation system. Cur was loaded into poloxamer 407 micelles and incorporated into citric acid (CA) cross-linked Cs hydrogels using a central composite design. The hydrogels were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), rheological tests, and in vitro experiments, such as hemolysis and cytotoxicity assays. FTIR confirmed cross-linking between Cs and CA, while DSC suggested interactions between Cur-loaded micelles and the hydrogel matrix. Rheological analysis revealed gel-like behavior, with G′ consistently higher than G, and temperature influenced hydrogel properties. SEM showed a denser network when Cur-loaded micelles were incorporated, slowing Cur release. At physiological pH (7.4), 75% of Cur was released after 7 days, while 84% was released at pH 5.5, showing pH-responsive behavior. Cytotoxicity tests showed over 80% viability of VERO CCL-81 cells (0.2–20 ppm hydrogel). This dual-encapsulation system provides a simple and effective platform for loading lipophilic drugs into pH-responsive hydrogels. Full article

Background/Objective: A clinical need exists for more effective therapeutics and sustained drug delivery systems to promote ocular surface healing. This study tested the hypothesis that a novel biodegradable, thermoresponsive hydrogel loaded with the human recombinant (rh)MG53 protein, which we have demonstrated to promote corneal healing without fibrosis, would exhibit safety and biocompatibility in vitro and in vivo. Methods: Hydrogel optimization was performed based on varying concentrations of poloxamer 407, poloxamer 188, and hydroxypropyl methylcellulose. Hydrogels were characterized and potential toxicity was evaluated in vitro in cultured corneal epithelium, fibroblasts, and endothelium. In vivo safety and tolerability were assessed in mice and hydrogels were used to evaluate corneal healing following alkali injury. Results: The optimized hydrogel formulation did not result in any detrimental changes to the corneal cells and released functional rhMG53 protein for at least 24 h. In vivo rhMG53-loaded hydrogels improved re-epithelialization, reduced stromal opacification and vascularization, and promoted corneal nerve density. Mechanistically, rhMG53 reduced vascular endothelial cell migration and tube formation by inhibiting pSTAT3 signaling. Conclusions: Taken together, our poloxamer-based thermoresponsive hydrogel effectively released rhMG53 protein and enhanced multiple corneal healing outcomes. Full article

The aim of this study was to investigate the influence of solid dispersion (SD) formulation factors on improvement of the bioavailability and pharmacokinetic profile of clopidogrel after peroral administration using an in vitro–in silico approach. A clopidogrel-specific, physiologically based biopharmaceutical model (PBBM) was developed and validated to predict absorption and distribution of clopidogrel after peroral administration of the tested formulations. Clopidogrel solid dispersions were prepared using two polymers (poloxamer 407 and copovidone) and a drug-to-polymer ratio of 1:5 and 1:9. The results of the in vitro dissolution test under pH–media change conditions showed that the type and ratio of polymers notably influenced the release of clopidogrel from the SDs. It can be observed that an increase in the polymer content in the SDs leads to a decrease in the release of clopidogrel from the SDs. The predictive power of the constructed clopidogrel-specific PBBM was demonstrated by comparing the simulation results with pharmacokinetic data from the literature. The in vitro dissolution data were used as inputs for the PBBM to predict the pharmacokinetic profiles of clopidogrel after the peroral administration of SDs. SDs with copovidone (1:5) and poloxamer (1:9) showed the potential to achieve the highest drug absorption and bioavailability, with an improvement of over 100% compared to an immediate-release (IR) tablet. The sample with poloxamer (1:9) may have the potential to reduce inter-individual variability in clopidogrel pharmacokinetics due to absorption in the cecum and colon and associated lower first-pass metabolism in the liver. This suggests that distal intestine may be the targeted delivery site for clopidogrel, leading to improved absorption and bioavailability of the drug. This study has shown that an in vitro–in silico approach could be a useful tool for the development and optimization of clopidogrel formulations, helping in decision making regarding the composition of the formulation to achieve the desired pharmacokinetic profile. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a significant pathogen playing a crucial role in causing bacterial infections of skin and soft tissues due to its high capacity for biofilm formation. Niosome-based gel systems offer significant potential for enhancing transdermal drug delivery and increasing the effectiveness of loaded drugs. The current research investigates the feasibility of niosomal gel for formulating the topical administration of teicoplanin (TEC). The thin film hydration method was used for niosome formulation was composed of nonionic surfactant, cholesterol, and mPEG 2000. TEC niosomal gel was prepared with adding hydroxypropyl methylcellulose (HPMC) and Poloxamer 407 polymers to the system. The physiochemical characteristics of prepared niosomal gel formulation, such as particle morphology, size, zeta surface charge, homogeneity, encapsulation efficiency, and in vitro drug release, were evaluated. Also, the in vitro antibacterial potential of the prepared system was analyzed. Further, we examined the in vivo antibacterial activity of the synthesized niosomal gel on infected wounds in Wister rats. We found that the TEC niosomal gel had antibacterial and anti-biofilm capabilities against MRSA isolates, and could be an effective wound material for preventing therapeutic problems related to this superbug. Full article

In this study, vesicular lipid systems and semi-solid formulations for the skin application of Palmitoyl-GHK were formulated and characterized. Palmitoyl-GHK is a cosmetic peptide with anti-aging action, capable of treating the signs of skin aging by mainly stimulating collagen synthesis in the dermis. The so-called “ethosomes” were evaluated as nanovesicular systems constituted of phosphatidylcholine, organized in vesicles, ethanol, and water. In addition, semi-solid systems were produced and characterized, namely an organogel based on phosphatidylcholine, isopropyl palmitate, and water, a gel based on Poloxamer 407, and the poloxamer organogel, created by combining organogel and Poloxamer gel. To make the ethosomal dispersions suitable for skin application, xanthan gum was added as a gelling agent. Studies were therefore carried out on semi-solid formulations to determine (i) the spreadability, a key factor that influences various aspects of a topical/transdermal formulation, (ii) the occlusive factor, important to guarantee good effectiveness of a dermocosmetic product, and finally, (iii) the hydrating power, to study the effect of a formulation applied to the skin. A formulation study enabled the selection of the most suitable formulations for the incorporation of the active ingredient of interest. Palmitoyl-GHK was found to be soluble both in ethosomes and in the poloxamer organogel. In vitro studies were therefore conducted to evaluate the release kinetics of Palmitoyl-GHK from the formulations, via Franz cells. The qualitative–quantitative analysis, through analytical HPLC, highlighted that the active ingredient is released more slowly from semi-solid formulations compared to vesicular systems; in particular, the presence of poloxamer allows a controlled release of the peptide. Further studies will be necessary to verify the anti-aging efficacy of formulations containing the peptide. Full article

Lidocaine is an analgesic agent frequently incorporated in topical formulations intended for application in minor surgical procedures or relieving neuropathic pain associated with numerous conditions, including post-herpetic neuralgia or diabetic peripheral neuropathy. In this study, Pickering o/w emulsions with halloysite nanotubes as a stabilizing agent and lidocaine incorporated in the internal phase were formulated with the use of the Quality by Design (QbD) approach. The selected emulsions were transformed into semisolid gels with poloxamer 407 as a thickening agent, and investigated for rheological and textural properties, indicating the mechanical features of the obtained gels. Moreover, the obtained formulations were tested for lidocaine release with the use of vertical Franz diffusion cells in order to assess the relationship between the applied composition and potential clinical applicability of the analyzed gels. The obtained results indicate that the emulsion droplet diameter is affected mostly by the oil and halloysite contents. The yield stress points, hardness and cohesiveness values of the obtained gels increased with the oil content. The drug release rate seems to be affected mostly by the concentration of the active ingredient in the oil phase. Full article

Hypericum perforatum L. (H.P.) is a species with a well-documented history of use in wound healing practices across the globe. The objective of this study was twofold: firstly, to evaluate the in vivo efficacy of liposomal in situ gel formulations in wound healing, both clinically and histopathologically, and secondly, to determine the physicochemical characterization of liposomal in situ gel formulations. The in vitro studies will be assessed in terms of particle size, zeta potential, release kinetics, rheological behaviors, and antioxidant and antimicrobial properties. The in vivo studies will be evaluated in clinical animal experiments and pathology studies. The in-situ hydrogel formulations were prepared using the physical cross-linking method with Poloxamer 188, Poloxamer 407, Ultrez 21, and Ultrez 30. The liposome formulations phospholipid 90H and lipoid S100 were prepared using the thin film solvent evaporation method. The antioxidant activity of the samples was evaluated through in vitro studies employing the DPPH antioxidant activity, ABTS+ test, and FRAP test. The antimicrobial activity of the samples was evaluated through the determination of MIC and MBC values employing the 96-well plate method. In vivo, 36 male New Zealand rabbits aged 32–36 weeks were utilized, with six rabbits in each group. The groups were composed of six distinct groups, including conventional and in situ gel liposome formulations of HHPM, three different commercial preparations, and a control group (n = 6). The HHPM-LG8 formulation developed in this study was found to be applicable in terms of all its properties. The new liposomal in situ hydrogel formulation demonstrated notable wound healing activity, a result that was supported by the formulation itself. Full article

Photodynamic therapy (PDT) is a light-activated chemical reaction used for the selective destruction of tissue. For this, various colorants may be applied, such as erythrosine (ERI), a dye already approved by the Food and Drug Administration (FDA) for various purposes. Although promising for PDT, ERI has a high hydrophilic profile that impacts its activity. To solve this, the combination of ERI with thermoresponsive and bioadhesive polymers may prove effective. Bio/mucoadhesive and thermoresponsive systems have attracted increasing interest in the development of novel pharmaceutical formulations for topical applications due to their ability to improve adhesion to the mucosa and prolong the residence time at the application site. In this study, systems based on poloxamer 407 (P407) in combination with cellulose derivatives (HPMC and NaCMC) were optimized, aiming at the topical release of ERI for PDT. The results demonstrated that the formulations containing low concentrations of cellulose derivatives exhibited greater adhesiveness and consistency at physiological temperature (37 °C), favoring the maintenance of the system at the application site. Regarding the gelation temperature (T_sol/gel), the formulations displayed values close to body temperature. The formulations with NaCMC showed a slightly higher T_sol/gel compared to HPMC ones, but it was adjustable by the polymer concentration. The addition of ERI influenced the mechanical and adhesive properties of the systems. In formulations containing HPMC, high concentrations of ERI increased bio/mucoadhesiveness, while in systems with NaCMC, the presence of ERI reduced this property. In both cases, the formulations maintained high consistency at 37 °C, contributing to the control of the active release at the application site. Rheological analysis revealed non-Newtonian behavior in all formulations, with greater consistency and elasticity at high temperatures. P407 was mainly responsible for the thermoresponsive transition from sol to gel, conferring desirable characteristics for topical application. Photodynamic activity was relevant in both formulations containing NaCMC and HPMC, which demonstrated greater capacity for degrading uric acid under light exposure. These systems are promising for the controlled release of drugs in photodynamic therapy, providing prolonged retention in the target tissue and maximizing the therapeutic efficacy of ERI. Full article

The topical administration of in situ hydrogels for ocular pathologies is a promising application strategy for providing high effectiveness and patient compliance. Curcumin, a natural polyphenol, possesses all the prerequisites for successful therapy of ophthalmic diseases, but unfortunately its physicochemical properties hurdle the practical use. Applying a composite in situ thermoresponsive hydrogel formulation embedded with polymer nanoparticles is a potent strategy to overcome all the identified drawbacks. In the present work we prepared uniform spherical nanoparticles (296.4 ± 3.1 nm) efficiently loaded with curcumin (EE% 82.5 ± 2.3%) based on the biocompatible and biodegradable poly-(lactic-co-glycolic acid). They were thoroughly physicochemically characterized in terms of FTIR, SEM, TGA, and DLS, in vitro release following Fickian diffusion (45.62 ± 2.37%), and stability over 6 months. Their lack of cytotoxicity was demonstrated in vitro on HaCaT cell lines, and the potential for antioxidant protection was also outlined, starting from concentrations as low as 0.1 µM and reaching 41% protection at 5 µM. An in situ thermoresponsive hydrogel (17% w/v poloxamer 407 and 0.1% Carbopol) with suitable properties for ophthalmic application was optimized with respect to gelation temperature (31.40 ± 0.36 °C), gelling time (8.99 ± 0.28 s) upon tears dilution, and gel erosion (90.75 ± 4.06%). Upon curcumin-loaded nanoparticle embedding, the in situ hydrogels demonstrated appropriate pseudoplastic behavior and viscosity at 35 °C (2129 ± 24 Pa∙s), 6-fold increase in the permeation, and prolonged release over 6 h. Full article

This study investigates the development and comprehensive characterization of innovative thermoresponsive gels incorporating rosemary essential oil (RoEO) encapsulated in poly(lactic-co-glycolic acid) (PLGA) microparticles, with a focus on their potential applications in topical antimicrobial and wound healing therapies. RoEO, renowned for its robust antimicrobial, antioxidant, and wound-healing properties, was subjected to detailed chemical profiling using gas chromatography-mass spectrometry (GC–MS), which identified oxygenated monoterpenes as its dominant constituents. PLGA microparticles were synthesized through an optimized oil-in-water emulsion technique, ensuring high encapsulation efficiency and structural integrity. These microparticles were thoroughly characterized using Fourier-transform infrared (FTIR) spectroscopy to confirm functional group interactions, scanning electron microscopy (SEM) for surface morphology, X-ray diffraction (XRD) for crystalline properties, and thermal analysis for stability assessment. The synthesized microparticles displayed uniform size distribution and efficient encapsulation, demonstrating compatibility with the gel matrix. Two distinct thermoresponsive gel formulations were developed using varying ratios of Poloxamer 407 and Poloxamer 188 to achieve optimal performance. The gels were evaluated for key physicochemical properties, including pH, gelation temperature, viscosity, and rheological behavior. Both formulations exhibited thermoresponsive gelation at skin-compatible temperatures (27.6 °C and 32.9 °C), favorable pH levels (6.63 and 6.40), and shear-thinning behavior suitable for topical application. Antimicrobial efficacy was assessed against common pathogens associated with skin infections, including Staphylococcus aureus, Escherichia coli, and Candida albicans. The RoEO-PLGA-loaded gels demonstrated significant inhibitory effects, confirming their potential as effective carriers for controlled and localized drug delivery. These findings underscore the promising application of RoEO-PLGA-loaded thermoresponsive gels in addressing challenges associated with topical antimicrobial therapies and wound care, offering an innovative approach to enhancing therapeutic outcomes. By integrating the bioactive potential of RoEO with the advanced delivery capabilities of PLGA microparticles and thermoresponsive gels, this study paves the way for the development of next-generation formulations tailored to meet the specific needs of localized drug delivery in skin health management. Full article

Trans-resveratrol (RES) is a natural polyphenol known for its antioxidant, anti-inflammatory, and anti-aging properties, making it highly valuable in cosmetic applications. Solid lipid nanoparticles (SLNs) offer a promising solution to enhance RES’s stability and cutaneous availability. This study aimed to develop and characterize SLNs encapsulating RES for enhanced skin delivery. Multiple methodologies were evaluated to determine the impact of preparation methods on formulation stability. SLNs were formulated using stearic acid, soy phosphatidylcholine, polysorbate 80, cetyltrimethylammonium bromide, and poloxamer 407, with variations in heating temperatures and homogenization techniques. Stability assessments were conducted over 90 days, examining organoleptic properties of the hydrodynamic diameter, polydispersity index, and zeta potential. Encapsulation efficiency and skin permeation studies were performed to investigate the efficacy of SLNs in delivering RES. Results demonstrated that formulations prepared with Ultra Turrax at 24,000 rpm and heating at higher temperatures exhibited enhanced stability and smaller particle sizes. The selected formulations, F1 (prepared at 80 °C) and F2 (prepared at 70 °C) presented encapsulation efficiencies of 70% and 72%, respectively. Skin permeation studies confirmed the ability of SLNs to facilitate RES delivery through the skin. The study concludes that SLNs are suitable carriers for RES skin delivery, offering improved stability and sustained release, thus representing a promising approach for topical applications to leverage RES’s cutaneous therapeutic benefits. Full article

Background/Objectives: This study aimed to evaluate the safety and efficacy of chitosan-based bioadhesive films for facilitating the topical delivery of curcumin in skin cancer treatment, addressing the pharmacokinetic limitations associated with oral administration. Methods: The films, which incorporated curcumin, were formulated using varying proportions of chitosan, polyvinyl alcohol, Poloxamer^® 407, and propylene glycol. These films were assessed for stability, drug release, in vitro skin permeation, cell viability (with and without radiotherapy), and skin irritation. Results: The films demonstrated physical stability and preserved curcumin content at room temperature for 90 days. Drug release was effectively controlled during the first 8 h, with release rates ranging from 51.6 ± 4.8% to 65.6 ± 13.0%. The films also enhanced drug penetration into the skin compared to a curcumin solution used as a control (stratum corneum: 1.3 ± 0.1 to 1.9 ± 0.8 µg/cm²; deeper skin layers: 1.7 ± 0.1 to 2.7 ± 0.2 µg/cm²). A cytotoxicity test on metastatic melanoma cells showed that curcumin at topical doses exerted activity similar to that delivered via the skin. Furthermore, curcumin alone was more effective in inhibiting tumor cells than radiotherapy alone (p < 0.01), with no additional benefit observed when curcumin was combined with radiotherapy. Finally, irritation tests confirmed that the films were safe for topical application. Conclusion: The developed chitosan-based bioadhesive films represent a promising alternative for the topical treatment of skin tumors using curcumin. Full article

Objectives: To design a multifunctional nanozyme hydrogel with antibacterial, photo-responsive nitric oxide-releasing, and antioxidative properties for promoting the healing of infected wounds. Methods: We first developed ultra-small silver nanoparticles (NPs)-decorated sodium nitroprusside-doped Prussian blue (SNPB) NPs, referred to as SNPB@Ag NPs, which served as a multifunctional nanozyme. Subsequently, this nanozyme, together with geniposide (GE), was incorporated into a thermo-sensitive hydrogel, formulated from Poloxamer 407 and carboxymethyl chitosan, creating a novel antibacterial wound dressing designated as GE/SNPB@Ag hydrogel. The physical properties of a GE/SNPB@Ag hydrogel were systematically investigated. Results: After embedding the nanozyme and GE, the resulting GE/SNPB@Ag hydrogel retains its thermosensitive properties and exhibits sustained release characteristics. In addition to its catalase-like activity, the nanozyme demonstrates high photothermal conversion efficiency, photo-induced nitric oxide release, and antibacterial activity. In addition, the hydrogel exhibits favorable antioxidant properties and high biocompatibility. The results of animal experiments demonstrate that the composite hydrogel combined with laser irradiation is an effective method for promoting infected wound healing. Conclusions: In vitro and in vivo studies indicate that the resulting GE/SNPB@Ag hydrogel holds significant potential for the treatment of infected wounds and for further clinical applications. Full article