Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

Transferosomes stabilized hydrogel incorporated rhodomyrtone-rich extract from Rhodomyrtus tomentosa leaf fortified with phosphatidylcholine for the management of skin and soft-tissue infections.

Rhodomyrtus tomentosa leaf (RT)-incorporated transferosomes were developed with lecithin and cholesterol blends with edge activators at different ratios. RT-transferosomes were characterized and employed in transferosomal gel formulations for the management of skin and soft-tissue infections. The optimized formulation entrapped up to 81.90 ± 0.31% of RT with spherical vesicles (405.3 ± 2.0 nm), polydispersity index value of 0.16 ± 0.08, and zeta potential of - 61.62 ± 0.86 mV. Total phenolic and flavonoid contents of RT-transferosomes were 15.65 ± 0.04 µg GAE/g extract and 43.13 ± 0.91 µg QE/g extract, respectively. RT-transferosomes demonstrated minimum inhibitory and minimum bactericidal concentrations at 8-256 and 64-1024 µg/mL, respectively. Free radical scavenging assay showed RT-transferosomes with high scavenging activity against DPPH and ABTS radicals. Moreover, RT-transferosomes demonstrated moderate activity against mushroom tyrosinase, with IC50 values of 245.32 ± 1.32 µg/mL. The biocompatibility results against L929 fibroblast and Vero cells demonstrated IC50 at 7.05 ± 0.17 and 4.73 ± 0.13 µg/mL, respectively. In addition, nitric oxide production significantly decreased by 6.78-88.25% following the treatment with 31.2-500 ng/mL RT-transferosomes (p < 0.001). Furthermore, the freeze-thaw stability study displayed no significant change in stability in the sedimentation and pH of gel fortified with RT-transferosomes. The results suggested that RT-transferosome formulation can be effectively employed as natural biomedicines for scar prevention and the management of skin soft-tissue infections.

Thyme Oil-Containing Fluconazole-Loaded Transferosomal Bigel for Transdermal Delivery.

The objective of the present research was to develop fluconazole-loaded transferosomal bigels for transdermal delivery by employing statistical optimization (23 factorial design-based). Thin-film hydration was employed to prepare fluconazole-loaded transferomal suspensions, which were then incorporated into bigel system. A 23 factorial design was employed where ratios of lipids to edge activators, lipids (soya lecithin to cholesterol), and edge activators (sodium deoxycholate to Tween 80) were factors. Ex vivo permeation flux (Jss) of transferosomal bigels across porcine skin was analyzed as response. The optimal setting for optimized formulation (FO) was A= 4.96, B= 3.82, and C= 2.16. The optimized transferosomes showed 52.38 ± 1.76% DEE, 76.37 nm vesicle size, 0.233 PDI, - 20.3 mV zeta potential, and desirable deformability. TEM of optimized transferosomes exhibited a multilamelar structure. FO bigel's FE-SEM revealed a globule-shaped vesicular structure. Further, the optimized transferosomal suspension was incorporated into thyme oil (0.1% w/w)-containing bigel (TO-FO). Ex vivo transdermal fluconazole permeation from different transferosomal bigels was sustained over 24 h. The highest permeation flux (4.101 µg/cm2/h) was estimated for TO-FO bigel. TO-FO bigel presented 1.67-fold more increments of antifungal activity against Candida albicans than FO bigel. The prepared thyme oil (0.1% w/w)-containing transfersomal bigel formulations can be used as topical delivery system to treat candida related fungal infections.

Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2.

Purpose: Immunomodulatory and broad-spectrum antiviral activities have motivated the evaluation of curcumin for Coronavirus infection 2019 (COVID-19) management. Inadequate bioavailability is the main impediment to the therapeutic effects of oral Cur. This study aimed to develop an optimal curcumin transferosome-loaded thermosensitive in situ gel to improve its delivery to the lungs. Methods: Transferosomes were developed by using 33 screening layouts. The phospholipid concentration as well as the concentration and type of surfactant were considered independent variables. The entrapment efficiency (EE%), size, surface charge, and polydispersity index (PDI) were regarded as dependent factors. A cold technique was employed to develop thermosensitive in-situ gels. Optimized transferosomes were loaded onto the selected gels. The produced gel was assessed based on shape attributes, ex vivo permeability enhancement, and the safety of the nasal mucosa. The in vitro cytotoxicity, antiviral cytopathic effect, and plaque assay (CV/CPE/Plaque activity), and in vivo performance were evaluated after intranasal administration in experimental rabbits. Results: The optimized preparation displayed a particle size of 664.3 ± 69.3 nm, EE% of 82.8 ± 0.02%, ZP of -11.23 ± 2.5 mV, and PDI of 0.6 ± 0.03. The in vitro curcumin release from the optimized transferosomal gel was markedly improved compared with that of the free drug-loaded gel. An ex vivo permeation study revealed a significant improvement (2.58-fold) in drug permeability across nasal tissues of sheep. Histopathological screening confirmed the safety of these preparations. This formulation showed high antiviral activity against SARS-CoV-2 at reduced concentrations. High relative bioavailability (226.45%) was attained after the formula intranasally administered to rabbits compared to the free drug in-situ gel. The curcumin transferosome gel displayed a relatively high lung accumulation after intranasal administration. Conclusion: This study provides a promising formulation for the antiviral treatment of COVID-19 patients, which can be evaluated further in preclinical and clinical studies.

Improved skin permeation of transferosomes containing Eulophia macrobulbon extract.

Eulophia macrobulbon (EM) extract-loaded transferosomes represent an advanced approach for enhancing skin permeation of bioactive compounds. The formulations improving skin permeation and characterizations of transferosomes were studied, including morphology, entrapment efficiency (EE), vesicle size, polydispersity index (PDI), zeta potential, and skin permeation in the Strat-M® synthetic membrane. Vesicle size increased with increasing transition temperature (Tm) of phosphatidylcholine and the hydrophilic-lipophilic balance (HLB) of the surfactant used as an edge activator. EM extract-loaded transferosomes with varying amounts of phosphatidylcholine, surfactants, and EM extract showed non-significant differences in EE, PDI, and zeta potential. The results demonstrated that the EM extract-loaded transferosomes improved membrane permeability better than the EM solution. The EM solution exhibited a shorter lag time. Considering the advantages of the EM extract-loaded transferosomes and EM solutions, a combination of both formulations was developed in this study. The results showed that the lag time decreased and membrane permeation increased. This study highlights a novel system combining EM extract-loaded transferosomes and an EM solution, exhibiting considerable improvement in skin permeation and presenting the potential for an efficient transdermal drug delivery system for natural bioactive compounds.

Formulation, optimization, and nephrotoxicity evaluation of an antifungal in situ nasal gel loaded with voriconazole‒clove oil transferosomal nanoparticles.

Fungal infections of the paranasal cavity are among the most widely spread illnesses nowadays. The aim of the current study was to estimate the effectiveness of an in situ gel loaded with voriconazole‒clove oil nano-transferosomes (VRC-CO-NT) in enhancing the activity of voriconazole against Aspergillus flavus, which causes rhinosinusitis. The nephrotoxic side effects of voriconazole may be reduced through the incorporation of the clove oil, which has antioxidant activity that protects tissue. The Box‒Behnken design was applied to formulate the VRC-CO-NT. The particle size, entrapment efficiency, antifungal inhibition zone, and serum creatinine concentration were considered dependent variables, and the soybean lecithin, VRC, and CO concentrations were considered independent ones. The final optimized formulation was loaded into a deacetylated gellan gum base and evaluated for its gelation, rheological properties, drug release profile, permeation capabilities, and in vivo nephrotoxicity. The optimum formulation was determined to be composed of 50 mg/mL lecithin, 18 mg/mL VRC, and 75 mg/mL CO, with a minimum particle size of 102.96 nm, an entrapment efficiency of 71.70%, an inhibition zone of 21.76 mm, and a serum creatinine level of 0.119 mmol/L. The optimized loaded in situ gel released 82.5% VRC after 12 hours and resulted in a 5.4-fold increase in drug permeation. The in vivo results obtained using rabbits resulted in a nonsignificant differentiation among the renal function parameters compared with the negative control group. In conclusion, nasal in situ gel loaded with VRC-CO-NT is considered an efficient novel carrier with enhanced antifungal properties with no signs of nephrotoxicity.

Dry Gel Containing Optimized Felodipine-Loaded Transferosomes: a Promising Transdermal Delivery System to Enhance Drug Bioavailability.

Felodipine has a very low bioavailability due to first-pass metabolism. The aim of this study was to enhance its bioavailability by transdermal application. Felodipine-loaded transferosomes were prepared by thin-film hydration using different formulation variables. An optimized formula was designed using statistical experimental design. The independent variables were the used edge activator, its molar ratio to phosphatidylcholine, and presence or absence of cholesterol. The responses were entrapment efficiency of transferosomes, their size, polydispersity index, zeta potential, and percent drug released after 8 h. The optimized formula was subjected to differential scanning calorimetry studies and its stability on storage at 4°C for 6 months was estimated. This formula was improved by incorporation of different permeation enhancers where ex vivo drug flux through mice skin was estimated and the best improved formula was formulated in a gel and lyophilized. The prepared gel was subjected to in vivo study using Plendil® tablets as a reference. According to the calculated desirability, the optimized transferosome formula was that containing sodium deoxycholate as edge activator at 5:1 M ratio to phosphatidylcholine and no cholesterol. The thermograms of this formula indicated the incorporation of felodipine inside the prepared vesicles. None of the tested parameters differed significantly on storage. The lyophilized gel of labrasol-containing formula was chosen for in vivo study. The relative bioavailability of felodipine from the designed gel was 1.7. In conclusion, topically applied lyophilized gel containing felodipine-loaded transferosomes is a promising transdermal delivery system to enhance its bioavailability.