Search Results (214)

Background/Objectives: Wound healing requires simultaneous pain control, inflammation management, infection prevention, and tissue regeneration. This study aimed to develop and evaluate in vitro a non-contact thermosensitive spray hydrogel combining lidocaine for rapid analgesia and allantoin for tissue repair. Methods: The effects of chitosan and Poloxamer 407 on viscosity, spray diameter, and bioadhesion ability of hydrogels were optimized using response surface methodology. Lead formulations (S1 and S2) were selected via a desirability function within the software. The pH, gelation temperature (T_G), rheological behavior, sprayability, bioadhesion, and lidocaine release using the dialysis bag method were assessed. The in vitro cytotoxicity, anti-inflammatory activity (TNF-α), and cell migration (scratch assay) of the formulations were investigated. Results: The viscosity values (42.7–58.7 mPa·s) indicated suitability for spraying at room temperature. T_G was 28.7 ± 0.6 °C (S1) and 29.3 ± 0.3 °C (S2), enabling rapid sol–gel transition at skin temperature. The lidocaine release reached 95–100% within 120 min. S2 exhibited lower viscosity and wider spray diameter, improving applicability on larger wound areas. In vitro cytotoxicity, scratch assay, and inflammatory marker analyses demonstrated that the optimized sprayable hydrogels exhibited a biocompatible and cell-healing profile. Conclusions: The developed thermosensitive spray hydrogel enables the combined delivery of lidocaine and allantoin, rapid gelation at body temperature, and touch-free administration. Its suitable viscosity and sprayability, and fast lidocaine release profile indicate high patient compliance and a significant advantage over conventional cream/ointment formulations, particularly regarding painless application, reduced contamination risk, enhanced therapeutic potential, and confirmed in vitro biocompatibility with supportive effects on keratinocyte behavior. Full article

p-coumaric acid is a natural phenolic compound with antioxidant activity, but its poor solubility and low bioavailability limit its practical use in oral formulations. The aim of this study is to evaluate how different polymers affect the dissolution and antioxidant properties of p-coumaric acid when incorporated into capsules and gels. Nine capsule compositions were prepared using poloxamer 407 (C1 group), sodium carboxymethyl cellulose (C2 group), chitosan (C3 group) and 5 hydrogels (G group) with the same polymers. The results indicate that p-coumaric acid is poorly soluble in aqueous solvents. The selected polymers modified the solubility of p-coumaric acid. The best solubility of p-coumaric acid was observed in mixtures containing 14.3% Poloxamer 407 (P407). The results showed that the polymers significantly affected the release kinetics of p-coumaric acid from the modeled capsules and gels. It was observed that capsules containing 14.3% P407 and gels with 14% P407 exhibited the best dissolution kinetics of p-coumaric acid. Antioxidant activity was strongest in formulations that released more p-coumaric acid. The results of this study confirm that the type and amount of excipients significantly affect the quality of capsules and gels. p-coumaric acid has the potential to be used in food supplements as a natural antioxidant, but further research is needed to improve its bioavailability and ensure safety. Full article

Background: Penfluridol is a long-acting oral antipsychotic used for the treatment of schizophrenia. Although the prolonged half-life of penfluridol allows once-weekly dosing, improving patient compliance, its therapeutic potential is limited by low aqueous solubility and poor oral absorption. This study aimed to enhance the dissolution and oral bioavailability of penfluridol using solid dispersion technology. Methods: Ternary solid dispersions of penfluridol were prepared using a solvent evaporation method with various hydrophilic carriers. Following prescreening of polymeric carriers, the formulation composition was optimized using a random forest regression model. Structural characteristics and drug release behavior of the optimized formulation (PF-SD5) were evaluated through in vitro studies. Pharmacokinetic studies in rats were conducted to assess the effectiveness of PF-SD5 in enhancing oral bioavailability. Results: The optimized PF-SD5 formulation, comprising penfluridol, poloxamer 407, and polyvinylpyrrolidone K30 in a 1:3:1 ratio, exhibited a 117-fold increase in aqueous solubility compared with the pure drug. PF-SD5 achieved nearly complete drug release within 1 h across a pH range from acidic to neutral. Spectroscopic, microscopical, and thermal analyses confirmed that penfluridol transformed into an amorphous form and established molecular interactions within the carrier matrix. Pharmacokinetic studies in rats revealed approximately a 1.9-fold increase in oral bioavailability. Conclusions: Combining solid dispersion technology with machine learning-guided optimization provides an effective strategy for enhancing the oral absorption of poorly soluble penfluridol. Full article

Objectives: Surfactants are commonly incorporated into amorphous solid dispersions (ASDs) to improve manufacturing and enhance the dissolution of poorly water-soluble drugs. However, their impact on in vitro dissolution, in vivo bioavailability, and in vitro-in vivo correlation (IVIVC) remains poorly understood, impeding the rational design of ASDs. This study aimed to elucidate the impact of six surfactants: anionic sodium lauroyl glutamate (SLG), sodium taurocholate (NaTC), sodium lauryl sulfate (SLS), and non-ionic polysorbate 80 (TW80), poloxamer 188 (P188), and polyoxyethylene lauryl ether (Brij-35), on the performance of paclitaxel (PTX)/HPMC-AS ASD. Methods: Binary PTX/HPMC-AS and ternary PTX/HPMC-AS/surfactant ASDs were prepared via rotary evaporation for FT-IR study. For dissolution and pharmacokinetic studies, low drug-loading formulations were prepared by physically blending PTX/HPMC-AS ASD with surfactants. Drug–polymer–surfactant interactions were investigated using NMR and FT-IR techniques. Dissolution performance was systematically evaluated by analyzing: (1) solubility of crystalline PTX in HPMC-AS/surfactant solutions; (2) supersaturation sustaining capacity in HPMC-AS/surfactant solutions; (3) surfactant effects on ASD dissolution and supersaturation generation; and (4) phase transformation during ASD dissolution. In vivo bioavailability was assessed in rats. Results: Findings revealed surfactant-specific effects: (1) SLG and P188 minimally affected bioavailability of PTX/HPMC-AS ASD (p > 0.05), consistent with their negligible effect on dissolution, attributable to incompatibility with PTX/HPMC-AS and weak molecular interactions; (2) TW80 significantly reduced bioavailability (p < 0.001) by inducing crystallization; thereby diminishing the amorphous advantage; (3) NaTC, Brij-35, and SLS markedly increased bioavailability (p < 0.001), owing to their compatibility with PTX and HPMC-AS, which enhanced dissolution and maintained amorphous state of precipitates. Surfactants appear to modulate ASD performance by governing supersaturation generation in solution and maintaining amorphous stability in the undissolved solid. Conclusions: The dissolution and bioavailability of ASDs are fundamentally controlled by compatibility between drug, polymer, and surfactant. Surfactant selection critically impacts ASD bioavailability. Comprehensive dissolution characterization, including supersaturation kinetics and precipitate phase analysis, enables prediction of bioavailability. Integrating molecular-level interaction analysis with multidimensional dissolution profiling is therefore essential for rational ASD design. Full article

Surgical site infections in oral and maxillofacial interventions are often exacerbated by biofilm formation, and current antimicrobial treatments are hampered by issues such as resistance and adverse effects. This article aimed to develop, characterize, and evaluate the antimicrobial activity of Lippia sidoides Cham. essential oil (LSEO) gel composed of poloxamer (P) and chitosan (C). Gas chromatography–mass spectrometry (GC-MS) analysis identified thymol as the major component of LSEO (71.04%). In situ P-gels containing LSEO (0.25–1.0%) were produced with and without C. The addition of C resulted in gels with nanometric particle sizes (263.8 ± 231 nm; PDI 0.39 ± 0.17) and a positive zeta potential (+4.81 ± 1.97 a + 8.19 ± 0.51 mV), exhibiting pseudoplastic behavior in rheological analysis. The sol–gel transition temperature (Tsol–gel) was found to be between 20 and 28 °C, with a transition time at 37 °C ranging from 18.76 ± 1.24 s to 46.46 ± 8.89 s. LSEO showed MIC values of 256, 128, and 128 µg/mL against Staphylococcus aureus, Escherichia coli, and Candida albicans, respectively, while in situ LSEO gels presented MIC values above 5 µg/mL for all tested strains. Therefore, the developed gel containing LSEO showed promising application in dentistry, offering a potential new treatment perspective for surgical site infections in oral and maxillofacial surgery. Full article

Background: Anemoside B4 (AB4), the major bioactive saponin from Pulsatilla chinensis, exhibits anti-inflammatory, anti-tumor, anti-apoptotic, and analgesic properties. However, its clinical translation for ulcerative colitis (UC) is constrained by poor epithelial permeability and low oral bioavailability. Objective: This study’s objective was to engineer and optimize thermosensitive rectal in situ gels (ISGs) of AB4, incorporating suitable absorption enhancers to improve mucosal permeation, bioavailability, and therapeutic efficacy against UC. Methods: Screening of effective permeation enhancers was conducted using Caco-2 cell monolayers and Franz diffusion cells. Critical formulation variables such as poloxamer 407 (P407), poloxamer 188 (P188), and hydroxypropyl methyl cellulose (HPMC) were optimized, employing single-factor experiments coupled with the Box–Behnken design response surface methodology (BBD-RSM). Comprehensive characterization encompassed in vitro release kinetics, in vivo pharmacokinetics, rectal tissue tolerability, rectal retention time, and pharmacodynamic efficacy in a UC model. Results: We used 2.5% hydroxypropyl-β-cyclodextrin (HP-β-CD) and 1.0% sodium caprate (SC) as the appropriate absorption enhancers, and the amounts of P407, P188, and HPMC were 17.41%, 4.07%, and 0.44%, respectively, to yield the corresponding in situ gels HP-β-CD-AB4-ISG and SC-AB4-ISG. The gel characterization, such as gelation temperature, gelation time, pH, gelation strength, etc., was in accordance with requirements. The ISGs did not stimulate or damage rectal tissue and remained in the rectum for a prolonged period. More importantly, an improvement in bioavailability and alleviation of UC were noted. Conclusion: Absorption enhancer-assisted, poloxamer-based thermosensitive rectal ISGs provide a safe, convenient, and effective platform for targeted delivery of AB4 to the colorectum. This strategy addresses key limitations of oral dosing and warrants further clinical development for UC and related colorectal inflammatory diseases. Full article

Background: Solid dispersions (SDs) of etodolac (ETD), a poorly water-soluble drug model, were developed to enhance its solubility and dissolution rate by employing various preparation methods and hydrophilic or amphiphilic polymers. Methods: Polyvinylpyrrolidone-poly(vinyl acetate) copolymers (PVP/VA), hydroxypropyl methylcellulose (HPMC) and poloxamer were used as carriers, while cryo-milling and lyophilization were utilized as routine methods to SDs preparation. Obtained SDs were characterized by drug content, solubility, dissolution rate and moisture content. The physical structure of SDs was estimated via scanning electron microscopy (SEM), whereas differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were employed to assess the potential drug-carrier interactions. Results: SD formulations demonstrated enhanced solubility of ETD in aqueous media, including water and buffers (pH 5.5 and 7.4). DSC analysis confirmed that PVP/VA and poloxamer ensured better ETD dissolution and protection against recrystallization. Furthermore, FTIR indicated the formation of hydrogen bonds between ETD and polymer, particularly in lyophilized dispersions. Conclusions: The optimized SD formulation for ETD contained PVP/VA and/or poloxamer as carriers and was obtained via lyophilization. This SD formulation exhibited the most favorable properties, enhanced the solubility and dissolution of ETD in aqueous media and effectively reduced its crystallinity. Full article

This article presents the results of a study on the rheological characteristics of in situ thermosensitive nasal gels based on poloxamer 407 (P407) and their effect on spray angle. The development of new drug delivery systems based on in situ thermosensitive gels can overcome several shortcomings of traditional nasal sprays associated with mucociliary clearance and low mucoadhesion. Using the cold method, samples based on P407 were prepared in pure form, in combination with poloxamer 188 (P188), and with the addition of several mucoadhesive polymers: chitosan, sodium alginate, and hydroxypropyl methylcellulose (HPMC). Analytical studies were carried out for all obtained samples, which showed that the gelling temperature (T_sol–gel) of compositions with P407 was inversely dependent on its concentration, decreasing from 32.71 °C to 24.63 °C. The addition of hydrophilic P188 increased T_sol–gel. The addition of mucoadhesive polymers had varying effects on T_sol–gel: chitosan and HPMC increased the temperature, while sodium alginate decreased it. The addition of mucoadhesive polymers significantly affected the viscosity of the formulations; for example, the addition of sodium alginate resulted in a fivefold increase, making the formulations unsuitable for spraying. A study of the spray angles of T_sol–gel samples in the range of 27–31 °C using the SprayVIEW measuring system revealed an inverse relationship between the viscosity of the formulations and the spray angle. A mathematical model of the solution droplet trajectory was presented, enabling the spray angle to be predicted depending on the formulation composition. The relative error of the computational experiments did not exceed 10%. This approach has the potential to reduce the number of full-scale experiments, and consequently their cost. Full article

Background/Objectives: Lidocaine hydrochloride (LD-HCl) is the most commonly used local anesthetic in dentistry, often administered with epinephrine to extend its duration and reduce systemic absorption. However, its relatively short duration of action, the need for repeated injections, and the unpleasant taste may limit patient compliance and procedural efficiency. This study aimed to develop and evaluate a novel injectable nanoemulsion-based in situ gel depot system of LD to provide prolonged anesthetic activity. Methods: LD-loaded nanoemulsions were formulated by high-shear homogenization followed by probe sonication, employing Miglyol 812 N (oil phase), a combination of Tween 80 and soy lecithin (surfactant–co-surfactant), glycerin, and deionized water (aqueous phase). The selected nanoemulsion (S1) was dispersed in a thermoreversible poloxamer solution to form a nanoemulgel. The preparation was evaluated for globule diameter and uniformity, zeta potential, surface morphology, pH, drug content, stability, rheological behavior, injectability, and in vitro drug release. Analgesic efficacy was assessed via tail-flick and thermal paw withdrawal latency tests in Wistar rats. Cardiovascular safety was monitored using non-invasive electrocardiography and blood pressure measurements. Results: The developed nanoemulsions demonstrated a spherical shape, nanometer size (206 nm), high zeta-potential (−66.67 mV) and uniform size distribution, with a polydispersity index of approximately 0.40, while the nanoemulgel demonstrated appropriate thixotropic properties for parenteral administration. In vitro release profiles showed steady LD release (5 h), following the Higuchi model. In vivo studies showed significantly prolonged analgesic effects lasting up to 150 min (2.5 h) compared to standard LD-HCl injection (p < 0.001), with no adverse cardiovascular effects observed. Conclusions: The developed injectable LD in situ nanoemulgel offers a promising, patient-friendly alternative for prolonged anesthetic delivery in dental and operative procedures, potentially reducing the need for repeated injections and enhancing procedural comfort. Full article

Background: Amlodipine besylate (AML) is recognized as a calcium channel blocker curative for hypertension. However, the drug emerged recently as an antibacterial cure that competently prevails over resistant strains. Methods: Incorporating amlodipine into zein nanoparticles was employed to innovate a suitable carrier for loading and targeting deep corneal infection. The Box–Behnken design was adopted to produce various formulations of amlodipine-loaded zein nanoparticles (AML-ZNs) with diversity in composition concentration (% w/v), comprising zein, Labrafac, and poloxamer 407. Results: Relying on the optimization criterion, the chosen preference formulation concentration (% w/v) consists of 2.068 for zein, 0.75 for Labrafac, and 1.0 for Poloxamer. Morphological micrography of AML-ZNs showed regular spherical particles in the nanometric scale, and physicochemical characterization procedures confirmed system suitability. While tracking eyedrop optimum features, sodium alginate was selected for coating nanoparticles to improve stability and system viscosity. Both pH and sterility were also considered and maintained. Comparative studies were conducted pre- and post-coating, and the assessed features for the final selected formulation were 349.9 ± 5.8 nm, 0.2186 ± 0.0271, −55.45 ± 1.84 mV, 81.293 ± 0.9%, and 19.3 ± 0.19 cp for size, PDI, surface charge, entrapment, and viscosity, respectively. The AML-ZNs-Alg formulation demonstrates a more controlled pattern of release of roughly 40% of the drug released after 48 h, while the permeation profile shows 37 ± 3.52% permeated after 24 h, confirmed visually. In vitro microbial assay alongside the corneal in vivo microbial and histological pathology evaluation proved the efficacy of amlodipine as an antibacterial agent. Conclusions: These findings highlighted that the prepared AML-ZNs-Alg eyedrop can be a promising system as an antibacterial therapy. Full article

Background/Objectives: Encouraged by the traditional use of Cotinus coggygria Scop. (European smoketree) for its anti-inflammatory and antioxidant properties, and considering the limitations of current therapies for recurrent aphthous stomatitis (RAS), we aimed to develop and evaluate a mucoadhesive oral gel containing C. coggygria stem bark extract. Methods: A thermosensitive gel was formulated using Carbopol^® 974P NF and poloxamer 407, enriched with 5% C. coggygria extract (CC gel), and characterized for its organoleptic properties, pH, electrical conductivity, and storage stability over six months. Therapeutic efficacy was assessed in a Wistar albino rat model of chemically induced oral ulcers. Animals were divided into three groups: untreated controls (CTRL), rats treated with gel base (GB), and those treated with CC gel over a 10-day period. Healing progression was monitored macroscopically (ulcer size reduction), biochemically (oxidative stress markers in plasma and tissue), and histologically. Results: The CC gel demonstrated satisfactory physicochemical stability and mucosal compatibility. Moreover, it significantly accelerated ulcer contraction and achieved complete re-epithelialization by day 6. Biochemical analyses revealed reduced TBARS and increased SOD, CAT, and GSH levels in ulcer tissue, indicating enhanced local antioxidant defense. Histological evaluation confirmed early resolution of inflammation, pronounced fibroblast activity, capillary proliferation, and full epithelial regeneration in the CC group, in contrast to delayed healing and persistent inflammatory infiltration in the GB and CTRL groups. Conclusions: These findings indicate that the CC gel has potential as a natural, topical formulation with antioxidant and regenerative properties for RAS, although further studies, including clinical evaluation, are required to confirm its overall efficacy and long-term safety. Full article

In ophthalmology, developing effective drug delivery systems is crucial to overcome anatomical and physiological barriers, such as rapid tear turnover and blinking, which limit the efficacy of conventional formulations like eye drops. Poloxamers, especially the derivatives 407 (P407) and 188, are amphiphilic triblock copolymers characterized by an intriguing thermo-reversible behavior, making them ideal candidates for the development of in situ hydrogels for ocular applications. Various thermo-sensitive poloxamer-based hydrogels were designed to be easily instilled as liquids at room temperature, gelling promptly upon contact with the corneal surface. These systems promoted a controlled release of active compounds, significantly improving their adhesion to the ocular surface. This review discusses the most relevant scientific literature on the topic, with particular attention to studies published in recent years. The results demonstrated that poloxamer formulations are capable of overcoming typical ocular barriers, thereby increasing drug bioavailability. The intrinsic biocompatibility of poloxamers contributes to the safety and tolerability of the system. Furthermore, P407 showed additional wound healing features. The combination of biocompatibility and thermo-reversible behavior makes poloxamer-based hydrogels a promising platform for the development of innovative ocular drug delivery systems able to enhance therapeutic efficacy and patient comfort. Full article

Background/Objectives: This study presents the development and characterization of a novel thermoresponsive hydrogel composed of hyaluronic acid (HA), poloxamer 407, cannabidiol (CBD), and colloidal silver (Ag), designed for topical antimicrobial therapy. Methods: The Ag-CBD complex was first synthesized and subsequently incorporated into a HA–poloxamer gel matrix to produce a stable, sprayable formulation with suitable physicochemical properties for dermal applications. Results: The HA-Ag-CBD hybrid gel exhibited a physiological pH, a gelation temperature compatible with skin surface conditions, and favorable rheological behavior, including thixotropy and shear thinning—critical for uniform application and retention under dynamic conditions. Release studies confirmed a sustained delivery profile, supporting prolonged local activity of CBD and colloidal Ag. Antimicrobial assays demonstrated that the HA-Ag-CBD hybrid gel retained potent activity against Staphylococcus aureus and Candida albicans, with minimum inhibitory and bactericidal concentrations (MIC/MBC) statistically comparable to those of the unencapsulated Ag-CBD complex. Against E. coli, the HA-Ag-CBD hydrogel exhibited primarily bacteriostatic activity, with a low MIC (9.24 μg/mL) but a substantially higher MBC (387.35 μg/mL), consistent with the intrinsic structural resistance of Gram-negative bacteria. In contrast, bactericidal activity was more pronounced against Gram-positive strains, reflecting differential susceptibility related to bacterial envelope properties. CBD consistently demonstrated superior antimicrobial efficacy to colloidal Ag, while the Ag-CBD combination produced slightly enhanced, mainly additive effects, likely due to complementary membrane disruption and intracellular Ag⁺ ion activity. Cytotoxicity assays on normal human dermal fibroblasts confirmed that the HA-Ag-CBD hybrid gel maintained >70% cell viability at therapeutically relevant concentrations, in accordance with ISO 10993-5:2009 guidelines, and effectively mitigated the inherent cytotoxicity of the Ag-CBD complex. Conclusions: The HA-Ag-CBD hybrid gel demonstrates strong potential as a biocompatible, multifunctional topical formulation for the treatment of infected wounds and skin lesions. Future work will focus on in vivo evaluation, assessment of skin permeation, and further development to support translational applications. Full article

Background/Objectives: This study aimed to enhance the vaginal permeation of buserelin acetate (BA), a synthetic gonadotropin-releasing hormone (GnRH) analogue, by evaluating various permeation enhancers (PEs) using a validated reversed-phase high-performance liquid chromatography (RP-HPLC) method and an ex vivo porcine vaginal model. Methods: A robust RP-HPLC method was developed and validated according to ICH Q2 (R2) guidelines to enable accurate quantification of BA in permeation samples. The analytical method demonstrated high specificity, linearity (R² = 0.9999), accuracy (98–102%), precision (%RSD < 2%), robustness, and stability. Using this method, ex vivo permeation studies were conducted with six different PEs: 2-hydroxypropyl-β-cyclodextrin, sodium dodecyl sulfate, poloxamer 188, Span 80, Tween 80, and chitosan. Results: Among all tested PEs, chitosan demonstrated the best enhancement of BA permeation. It achieved the highest flux (J) (0.64 ± 0.03 × 10⁻² µg/cm²·h) and apparent permeability coefficient (P_app) (16.20 ± 0.84 × 10⁻⁵ cm/h), both of which were statistically significantly higher (p < 0.05) than those of all other enhancer groups. Kinetic modelling indicated a non-Fickian, biphasic permeation mechanism best described by the Makoid–Banakar model. Conclusions: These findings highlight chitosan’s potential as an effective intravaginal delivery vehicle for peptide therapeutics and establish the validated HPLC method as a reliable platform for future formulation development and translational studies in mucosal drug delivery. Full article

Background/Objectives: This study aimed to develop a nanostructured lipid carrier (NLC) system incorporating a catechin-rich Vanda coerulea extract for topical cosmetic applications and to evaluate its physicochemical properties, release behavior, and skin retention performance. Methods: Blank NLCs were prepared using hot emulsification followed by sonication, with glyceryl monostearate, caprylic triglyceride, Poloxamer^® 188, and Tween^® 80 as the formulation components. NLCs with varying solid-to-liquid lipid ratios were developed while maintaining a constant total lipid content of 5% w/w. The formulations were characterized based on their particle size, polydispersity index (PDI), zeta potential, and physical stability, including stability after a heating–cooling cycle test. The effect of ultrasonication duration was also evaluated. The optimized NLC was then loaded with a V. coerulea extract and evaluated for in vitro release and skin retention using catechin as a marker. Results: The NLC with a particle size of 235.5 ± 29.8 nm, a narrow PDI range of 0.382 ± 0.090, and a strong zeta potential of −29.8 ± 0.3 mV was selected for the incorporation of the V. coerulea extract. The extract-loaded NLC exhibited a sustained release over 24 h, significantly different from the V. coerulea extract solution (p < 0.05). Skin retention studies revealed that the NLC achieved approximately twice the catechin retention compared to the solution at the 1 h time point (1.30 ± 0.01% vs. 0.68 ± 0.03% w/w). Conclusions: The V. coerulea-extract-loaded NLC demonstrated favorable physicochemical properties, sustained release behavior, and enhanced skin retention. These findings support its potential as a promising topical delivery system for antioxidant-rich botanical extracts in cosmetic applications. Full article