Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (biopharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of −26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm²/h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentration was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.

The current study depicts the comparative effects of nanogel using Withania coagulans extract, pregabalin alone, and a co-combination gel. The gels prepared were then analyzed for conductivity, viscosity, spread ability, globule size, zeta potential, polydispersity index, and TEM. The globule size of the co-combination gel, determined by zeta sizer, was found to be (329 ± 0.573 nm). FTIR analysis confirms the successful development of gel, without any interaction. Drug distribution at the molecular level was confirmed by XRD. DSC revealed no bigger thermal changes. TEM images revealed spherical molecules with sizes of 200 nm for the co-combination gel. In vivo studies were carried out by infliction of third degree burn wounds on rat skin, and they confirmed that pregabalin and Withania coagulans heals the wound more effectively, with a wound contraction rate of 89.95%, compared to remaining groups. Anti-inflammatory activity (IL-6 and TNF-α), determined by the ELISA technique, shows that the co-combination gel group reduces the maximum inflammation with TNF-α value (132.2 pg/mL), compared to the control (140.22 pg/mL). Similarly, the IL-6 value was found to be (78 pg/mL) for the co-combination gel and (81 pg/mL) in the case of the control. Histopathologically, the co-combination gel heals wounds more quickly, compared to individual gel. These outcomes depict that a co-combination gel using plant extracts and drugs can be successfully used to treat burn injury.

The current study reports the fabrication of co-combination gel using Pregabalin and Withania coagulans fruit extract to validate its effectiveness for neuropathic pain in chronic constriction injury (CCI) rat models. Three topical gels were prepared using Carbopol 934 through a pseudo-ternary phase diagram incorporating the Pregabalin (2.5%), Withania coagulans extract (2%), and co-combination of both Pregabalin (2.5%) and Withania coagulans extract (2%). Gels were characterized. FTIR showed a successful polymeric network of the gel without any interaction. The drug distribution at the molecular level was confirmed by XRD. The AFM images topographically indicated the rough surface of gels with a size range from 0.25 to 330 nm. DSC showed the disappearance of sharp peaks of the drug and extract, showing successful incorporation into the polymeric network of gels. The in vitro drug release of co-combination gel was 73% over 48 h. The mechanism of drug release by combination gel was Higuchi+ fickian with values of n (0.282) and R² (0.947). An in vivo study for pain assessment via four methods: (i) heat hyperalgesia, (ii) cold allodynia, (iii) mechano-hyperalgesia, and (iv) dynamic mechano-allodynia, confirmed that topical treatment with co-combination gel reduced the pain significantly as indicated by the p value: R1 (p < 0.001), R2 (p < 0.001), R3 (p < 0.015), and R4 (p < 0.0344). The significance order was R2 (****) > R1 (***) > R3 (**) > R4 (*) > R5 (ns).

Itraconazole (ITZ) is a broad-spectrum antifungal for superficial subcutaneous and systemic fungal infections. This study aimed to enhance the antifungal activity of ITZ using surfactin A (SA), a cyclic lipopeptide produced by the SA-producing Bacillus strain NH-100, possessing strong antifungal activity. SA was extracted, and ITZ-loaded SA micelles formulations were prepared via a single-pot rinsing method and characterized by particle size, zeta potential, and infrared spectroscopy. In vitro dissolution at pH 1.2, as well as hemolysis studies, was also carried out. The fabricated formulations were stable and non-spherical in shape, with an average size of about 179 nm, and FTIR spectra depicted no chemical interaction among formulation components. ITZ-loaded micelles showed decreased hemolysis activity in comparison to pure ITZ. The drug released followed the Korsmeyer–Peppas model, having R² 0.98 with the diffusion release mechanism. In an acidic buffer, drug release of all prepared formulations was in the range of 73–89% in 2 h. The molecular simulation showed the outstanding binding and stability profile of the ITZ-SA complex. The aromatic ring of the ITZ mediates a π-alkyl contact with a side chain in the SA. It can be concluded that ITZ-loaded micelles, owing to significant enhanced antifungal activity up to 6-fold due to the synergistic effect of SA, can be a promising drug delivery platform for delivery of poorly soluble ITZ.

Herein, a copolymeric hydrogel comprising a naturally occurring swellable biopolymer, i.e., glucoxylan (a major polysaccharide of chia seed mucilage (CM)) and methacrylic acid (MA), was synthesized through free radical polymerization for wound healing applications. The formation of CM-co-MA was authenticated through FTIR spectroscopy. The CM-co-MA appeared non-hemolytic and non-thrombogenic, and exhibited noteworthy antioxidant potential with DPPH scavenging activity ranging from 18.68 to 47.70 µg AAE µg/mL, FRAP activity from 32.22 to 63.70 µg AAE µg/mL, TFC from 27.91 to 73.59 µg QE/mL, and TPC from 26.95 to 58.21 µg GAE/mL. The CM-co-MA showed antibacterial activities against Listeria monocytogenes (Gram-positive) and Escherichia coli (Gram-negative), having a zone of inhibition (ZOI) of 27.87 and 23.00 mm, respectively. The antifungal activities were recorded against Aspergillus flavus and Candida albicans, and found the length of growth inhibition of 72 and 76 mm, respectively. The acute oral toxicity study, acute dermal toxicity, and eye irritation test demonstrated the non-toxic, innocuous, and non-irritant attributes of the CM-co-MA, respectively. All animals stayed alive without any significant abnormalities during the 14 day study, and all hematological and biochemical parameters of the control and experimental group animals were comparable. Histopathology of the vital organs of rabbits also showed normal cellular architecture without any abnormalities. A wound healing study on rabbits revealed the tissue regeneration, with 84.40% recovery in treated rabbits after 14 days, and comparable with the positive control. Hence, the CM-co-MA is considered a non-toxic material having haemocompatibility, antioxidant, antibacterial, and antifungal activities for potential application in wound healing.

Herein, a copolymeric hydrogel comprising a naturally occurring swellable biopolymer, i.e., glucoxylan (a major polysaccharide of chia seed mucilage (CM)) and methacrylic acid (MA), was synthesized through free radical polymerization for wound healing applications. The formation of CM-co-MA was authenticated through FTIR spectroscopy. The CM-co-MA appeared non-hemolytic and non-thrombogenic, and exhibited noteworthy antioxidant potential with DPPH scavenging activity ranging from 18.68 to 47.70 µg AAE µg/mL, FRAP activity from 32.22 to 63.70 µg AAE µg/mL, TFC from 27.91 to 73.59 µg QE/mL, and TPC from 26.95 to 58.21 µg GAE/mL. The CM-co-MA showed antibacterial activities against Listeria monocytogenes (Gram-positive) and Escherichia coli (Gram-negative), having a zone of inhibition (ZOI) of 27.87 and 23.00 mm, respectively. The antifungal activities were recorded against Aspergillus flavus and Candida albicans, and found the length of growth inhibition of 72 and 76 mm, respectively. The acute oral toxicity study, acute dermal toxicity, and eye irritation test demonstrated the non-toxic, innocuous, and non-irritant attributes of the CM-co-MA, respectively. All animals stayed alive without any significant abnormalities during the 14 day study, and all hematological and biochemical parameters of the control and experimental group animals were comparable. Histopathology of the vital organs of rabbits also showed normal cellular architecture without any abnormalities. A wound healing study on rabbits revealed the tissue regeneration, with 84.40% recovery in treated rabbits after 14 days, and comparable with the positive control. Hence, the CM-co-MA is considered a non-toxic material having haemocompatibility, antioxidant, antibacterial, and antifungal activities for potential application in wound healing.