Search Results (52)

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

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

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

Background/Objectives: A sustained-release formulation of fenofibrate while enhancing drug dissolution with minimal food effect is critical for maximizing the therapeutic benefits of fenofibrate. Therefore, this study aimed to develop an effective solid dispersion formulation of fenofibrate for simultaneous enhancement in the extent and duration of drug exposure. Methods: Fenofibrate-loaded solid dispersions (FNSDs) were prepared using poloxamer 407 and Eudragit^® RSPO at varied ratios via solvent evaporation. In vitro/in vivo characteristics of FNSDs were examined in comparison with untreated drugs. Results: Based on dissolution profiles of FNSDs in aqueous media, the weight ratio of fenofibrate: poloxamer 407: Eudragit^® RSPO at 1:1:4 (FNSD2) was selected as the optimal composition for achieving sustained drug release while maximizing the drug dissolution. The enhanced and sustained drug release of FNSD2 was also confirmed in a buffer transition system mimicking the pH change in the gastrointestinal tract. FNSD2 achieved approximately 66% drug release over 12 h, while pure drug exhibited only 12%. Furthermore, FNSD2 maintained similar release rates under fed and fasted conditions, while the entire drug dissolution slightly increased in the fed state. Structural analysis by x-ray diffraction showed that fenofibrate remained crystalline in FNSD2. Pharmacokinetic studies in rats revealed that orally administered FNSD2 significantly improved the extent and duration of systemic drug exposure. Compared to pure drugs, the FNSD2 formulation increased the oral bioavailability of fenofibrate by 22 folds with the delayed T_max of 4 h in rats. Conclusion: FNSD2 formulation is effective in improving the extent and duration of drug exposure simultaneously. Full article

Caffeic acid, a phenolic compound with antioxidant and antimicrobial properties, shows promise in the dermatological field. The research aimed to incorporate caffeic acid into hydrophilic gels based on poloxamer 407, carbomer 980, and their mixture in order to enhance its biological activity. Different gel formulations were prepared using different concentrations of these polymers to optimize caffeic acid release characteristics. The results showed that increasing the concentration of polymeric materials increased the viscosity and slowed down the release of caffeic acid. The antioxidant and antimicrobial activities of the gels were assessed. The results confirmed the potential of hydrophilic gels as delivery systems for caffeic acid, with formulations showing antimicrobial activity against Gram-positive Staphylococcus aureus bacteria and antifungal activity against Candida albicans fungus. This study provides a perception of the development of new semi-solid caffeic acid-based formulations for therapeutic and cosmetic applications. Full article

A targeted micellar formation of doxorubicin (Dox) and curcumin (Cur) was evaluated to enhance the efficacy and reduce the toxicity of these drugs in KG1a leukemic stem cells (LSCs) compared to EoL-1 leukemic cells. Dox-Cur-micelle (DCM) was developed to improve the cell uptake of both compounds in LSCs. Cur-micelle (CM) was produced to compare with DCM. DCM and CM were conjugated with two FLT3 (FMS-like tyrosine kinase)-specific peptides (CKR; C and EVQ; E) to increase drug delivery to KG1a via the FLT3 receptor (AML marker). They were formulated using a film-hydration technique together with a pH-induced self-assembly method. The optimal drug-to-polymer weight ratios for the DCM and CM formulations were 1:40. The weight ratio of Dox and Cur in DCM was 1:9. DCM and CM exhibited a particle size of 20–25 nm with neutral charge and a high %EE. Each micelle exhibited colloidal stability and prolonged drug release. Poloxamer 407 (P407) was modified with terminal azides and conjugated to FLT3-targeting peptides with terminal alkynes. DCM and CM coupled with peptides C, E, and C + E exhibited a higher particle size. Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells. Full article

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. Full article

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. Full article

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. Full article

In this study, we aimed to develop thermosensitive and bioadhesive in situ gelling systems containing solid dispersions of flurbiprofen (FB-SDs) using poloxamer 407 (P407) and 188 (P188) for ophthalmic delivery. FB-SDs were prepared with the melt method using P407, characterized by solubility, stability, SEM, DSC, TGA, and XRD analyses. Various formulations of poloxamer mixtures and FB-SDs were prepared using the cold method and P407/P188 (15/26.5%), which gels between 32 and 35 °C, was selected to develop an ophthalmic in situ gelling system. Bioadhesive polymers Carbopol 934P (CP) or carboxymethyl cellulose (CMC) were added in three concentrations (0.2, 0.4, and 0.6% (w/w)). Gelation temperature and time, mechanical properties, flow properties, and viscosity values were determined. The in vitro release rate, release kinetics, and the release mechanism of flurbiprofen (FB) from the ophthalmic formulations were analyzed. The results showed that FB-SDs’ solubility in water increased 332-fold compared with FB. The oscillation study results indicated that increasing bioadhesive polymer concentrations decreased gelation temperature and time, and formulations containing CP gel at lower temperatures and in a shorter time. All formulations except F3 and F4 showed Newtonion flow under non-physiological conditions, while all formulations exhibited non-Newtonion pseudoplastic flow under physiological conditions. Viscosity values increased with an increase in bioadhesive polymer concertation at physiological conditions. Texture profile analysis (TPA) showed that CP-containing formulations had higher hardness, compressibility, and adhesiveness, and the gel structure of formulation F4, containing 0.6% CP, exhibited the greatest hardness, compressibility, and adhesiveness. In vitro drug release studies indicated that CP and CMC had no effect below 0.6% concentration. Kinetic evaluation favored first-order and Hixson–Crowell kinetic models. Release mechanism analysis showed that the n values of the formulations were greater than 1 except for formulation F5, suggesting that FB might be released from the ophthalmic formulations by super case II type diffusion. When all the results of this study are evaluated, the in situ gelling formulations prepared with FB-SDs that contained P407/P188 (15/26.5%) and 0.2% CP or 0.2% CMC or 0.4 CMC% (F2, F5, and F6, respectively) could be promising formulations to prolong precorneal residence time and improve ocular bioavailability of FB. Full article

Biocompatible drug-delivery systems for soft tissue applications are of high interest for the medical and pharmaceutical fields. The subject of this research is the development of hydrogels loaded with bioactive compounds (inulin, thyme essential oil, hydro-glycero-alcoholic extract of Vitis vinifera, Opuntia ficus-indica powder, lactic acid, citric acid) in order to support the vaginal microbiota homeostasis. The nanofibrillar phyto-hydrogel systems developed using the biocompatible polymers chitosan (CS), never-dried bacterial nanocellulose (NDBNC), and Poloxamer 407 (PX) incorporated the water-soluble bioactive components in the NDBNC hydrophilic fraction and the hydrophobic components in the hydrophobic core of the PX fraction. Two NDBNC-PX hydrogels and one NDBNC-PX-CS hydrogel were structurally and physical-chemically characterized using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and rheology. The hydrogels were also evaluated in terms of thermo-responsive properties, mucoadhesion, biocompatibility, and prebiotic and antimicrobial effects. The mucin binding efficiency of hydrogel base systems was determined by the periodic acid/Schiff base (PAS) assay. Biocompatibility of hydrogel systems was determined by the MTT test using mouse fibroblasts. The prebiotic activity was determined using the probiotic strains Limosilactobacillus reuteri and Lactiplantibacillus plantarum subsp. plantarum. Antimicrobial activity was also assessed using relevant microbial strains, respectively, E. coli and C. albicans. TEM evidenced PX micelles of around 20 nm on NDBNC nanofibrils. The FTIR and XRD analyses revealed that the binary hydrogels are dominated by PX signals, and that the ternary hydrogel is dominated by CS, with additional particular fingerprints for the biocompounds and the hydrogel interaction with mucin. Rheology evidenced the gel transition temperatures of 18–22 °C for the binary hydrogels with thixotropic behavior and, respectively, no gel transition, with rheopectic behavior for the ternary hydrogel. The adhesion energies of the binary and ternary hydrogels were evaluated to be around 1.2 J/m² and 9.1 J/m², respectively. The hydrogels exhibited a high degree of biocompatibility, with the potential to support cell proliferation and also to promote the growth of lactobacilli. The hydrogel systems also presented significant antimicrobial and antibiofilm activity. Full article

This study investigates the influence of humidity on the dissolution behavior and microstructure of drugs in crystalline solid dispersions (CSDs). Using Bifonazole (BFZ) as a model drug, CSDs were prepared through spray drying with carriers such as Poloxamer 188 (P188), Poloxamer 407 (P407), and polyethylene glycol 8000 (PEG8000). The solubilization effect and mechanism were initially evaluated, followed by an examination of the impact of humidity (RH10%) on the dissolution behavior of CSDs. Furthermore, the influence of humidity on the microstructure of CSDs was investigated, and factors affecting the humidity stability of CSDs were summarized. Significant enhancements in the intrinsic dissolution rate (IDR) of BFZ in CSDs were observed due to changes in crystalline size and crystallinity, with the CSD-P188 system exhibiting the best performance. Following humidity treatment, the CSD-P407 system demonstrated the least change in the IDR of BFZ, indicating superior stability. The CSD-P407 system was followed by the CSD-P188 system, with the CSD-PEG8000 system exhibiting the least stability. Further analysis of the microstructure revealed that while humidity had negligible effects on the crystalline size and crystallinity of BFZ in CSDs, it had a significant impact on the distribution of BFZ on the CSD surface. This can be attributed to the water’s potent plasticizing effect, which significantly alters the molecular mobility of BFZ. Additionally, the compatibility of the three polymers with BFZ differs, with CSD-P407 > CSD-P188 > CSD-PEG8000. Under the continuous influence of water, stronger compatibility leads to lower molecular mobility and more uniform drug distribution on the CSD surface. Enhancing the compatibility of drugs with polymers can effectively reduce the mobility of BFZ in CSDs, thereby mitigating changes caused by water and ultimately stabilizing the surface composition and dissolution behavior of drugs in CSDs. Full article

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. Full article