Abdul Ahad

This work was undertaken to formulate invasomes for improved kaempferol (KAE) topical delivery. Cuminaldehyde (CUA)‐incorporated KAE invasomes were developed by thin film hydration by varying Phospholipon 90G, CUA, and ethanol. Developed formulations were characterized for vesicle size, polydispersity index, zeta potential, and entrapment efficiency. Finally, gel of optimized formulation was evaluated for in vitro drug release, antioxidant, and cell viability investigations. Optimized KAE invasomes (F5) formulation presented vesicle size of 168.63 ± 8.53 nm, polydispersity index of 0.284 ± 0.017, zeta potential of −14.52 ± 0.80, and entrapment efficiency of 81.56 ± 3.52%. The KAE invasomes gel and KAE control gel exhibited in vitro release of 74.10 ± 7.19% and 33.92 ± 4.55%, respectively. KAE invasomes gel exhibited improved antioxidant and cell viability activity compared to KAE control gel. Better activity of KAE invasomes gel is possible due to more effective solubilization of KAE entrapped in invasomes gel due to the presence of CUA and ethanol. In the stability study, KAE control gel and KAE invasomes gel did not show any significant changes in examined parameters. It can be concluded that CUA‐incorporated KAE invasomes are a promising formulation for enhanced delivery of KAE.

The purpose of the investigation was to formulate fisetin‐β‐cyclodextrin (βCD) binary inclusion complex employing solvent evaporation. A phase solubility study of fisetin was executed in the presence of βCD (2–10 mM). Fisetin‐binary inclusion complex was tested by DSC, FTIR, XRD, SEM, in vitro release, and cell viability measurements. A phase solubility test showed that fisetin solubility was elevated 4.11‐fold in the presence of βCD. The analysis of inclusion complex by DSC, FTIR, XRD, and SEM confirmed the formation of fisetin‐binary inclusion complex. Fisetin binary physical mixture and fisetin binary inclusion complex released 52.45% and 62.29% of drug, respectively. Higher drug released with inclusion complex could be due to formation of more water‐soluble inclusion complex. Fisetin binary inclusion complex exhibited significantly greater cytotoxicity on MCF‐7 cells than pure fisetin. A fisetin‐binary inclusion complex demonstrated a lower IC ₅₀ value (71.36 µM) than pure fisetin (102.20 µM). A solvent‐evaporation‐derived fisetin‐binary inclusion complex was found to facilitate fisetin solubility and drug release. Further, enhanced cellular toxicity was observed in binary inclusion complex compared to pure drug. Hence, solvent evaporation approaches in conjunction with cyclodextrin features offer a promising way to overcome the solubility challenges associated with molecules like fisetin.

Skin cancer is the most prevalent malignancy, with rising incidence and morbidity, particularly among the white population. This study aims to develop a dual drug-loaded nanoemulsion gel incorporating 5-fluorouracil (5-FU) and lepidine (LPD) to enhance drug deposition in the stratum corneum and dermal layer for improved skin cancer therapy. Oil-in-water (o/w) nanoemulsions were prepared using peppermint oil, Tween 80, and PEG-400 via aqueous phase titration method and optimized through pseudo-ternary phase diagrams. The optimized dual drug-loaded nanoemulsion showed particle size of 131.7 ± 3.21 nm, PDI of 0.21 ± 0.005, and zeta potential of -26.24 ± 1.532 mV. This nanoemulsion was then dispersed into a 1% carbopol 934 gel for topical application. In-vitro and ex-vivo studies demonstrated significantly enhanced drug deposition and prolonged release (**p < 0.001) compared to a conventional gel. Furthermore, dermatokinetic and CLSM studies confirmed enhanced skin permeation and deeper drug distribution. Skin irritation studies indicated that the nanoemulsion gel was safe and non-irritant. It is concluded that the developed 5-FU and LPD co-loaded nanoemulsion gel enhances topical drug delivery against skin cancer by improving drug absorption and distribution between the epidermis and dermis in rodent skin model, which could represent promising strategy for the management of skin cancer.

Background: Candida auris is a significant global health concern, due to its rapid transmission, high mortality rate, and resistance to commonly available antifungal drugs. Methodology: During the current study, a cationic polymeric hydrogel was developed using chitosan (CS), polyethylene glycol (PEG), and methacrylic acid (MAA). The respective solutions were mixed in a volumetric ratio of 2:1:1. After characterization, the hydrogel was assessed using antifungal, antibiofilm, and hemocompatibility assays. Results: The hydrodynamic radius of 554.7 ± 90.1 nm and zeta potential of 15.6 ± 1.09 mV indicate the ideal size and charge for topical applications and in vivo studies, respectively. The formulation exhibited improved thermal stability, enhanced swelling, and a drug release profile for non-Fickian diffusion. The hydrogel effectively inhibited fungal growth in agar plates (42 ± 7.31 mm zone of inhibition), with a mean IC₅₀ of 15.17 ± 4.01 μg/mL and MIC of 29.30 ± 11.72 μg/mL. Calcofluor white (CFW) staining showed diffuse irregular yeast cells, suggesting increased membrane permeability, eventually leading to cell death. The hemocompatibility assay revealed no visible agglutination or hemolysis at the MIC value. The formulation exhibited significantly reduced biofilm formation compared to the growth control (p < 0.05). Additionally, in silico analysis revealed that MAA showed superior oral bioavailability, no inhibitory activity on cytochrome P450 enzymes, and low potential for toxicity through nuclear receptor signaling pathways. Conclusions: Cationic hydrogels show promise as potential antifungal treatments. The development of cost-effective and improved therapeutic methods is crucial to combat this deadly pathogen and to improve patient outcomes.

Fisetin (FS) is a polyphenolic flavonoid possessing multiple biological activities along with broad nutraceutical applications. The low solubility of FS greatly limits its bioavailability and its use. The aim of the study was to prepare an FS ternary inclusion complex (TIC) using hydroxypropyl β‐cyclodextrin (HPβCD) and Poloxamer 188 (P188) by microwave technology. Phase solubility studies were performed in the presence of HPβCD (1 to 10 mM) and P188. The in vitro release of FS, ternary physical mixture (TPM) and FS‐TIC was determined. Additionally, DSC, FTIR, XRD, and SEM studies were performed on FS, TPM, and FS‐TIC to characterize the samples. Furthermore, FS‐TIC and pure FS were assessed for their antioxidant activity. The outcomes of the phase solubility study revealed that 6.33‐fold the solubility of FS was boosted in the presence of HPβCD/P188. FS and TPM demonstrated in vitro drug release of 34.09% and 62.29%, respectively. While a maximum in vitro drug release of 84.45% was obtained for FS‐TIC; this could be due to the formation of a water‐soluble inclusion complex. Results showed that FS release from TPM and TIC occurred through the Fickian diffusion mechanism and followed the Higuchi pattern. DSC, FTIR, XRD, and SEM analyses verified FS interaction with HPβCD and subsequently supported FS‐TIC formation. Furthermore, the developed FS‐TIC showed superior antioxidant activity compared to pure FS. It was concluded that the FS‐TIC prepared by microwave technique using HPβCD as a carrier provides a potential approach to facilitate FS solubility and drug release. In addition, microwave techniques combined with cyclodextrin/polymer properties present an intriguing approach to circumventing the solubility issue of poorly soluble compounds like fisetin.

This study aimed to provide an understanding of the influence of eugenol on CYP1A2, 2C9, 2D6, and 3A4 in human liver microsomes (HLM). Specific substrate for CYP1A2, 2C9, 2D6, and 3A4 were incubated in HLM with or without eugenol. The formation of their respective metabolites was assessed with HPLC analytical methods. Eugenol at 1, 10 and 100 µM levels inhibited the activity of CYP1A2 and CYP2C9 by 23.38 %, 23.57 %, 39.80 % and 62.82 %, 63.27 %, 67.70 % respectively. While, CYP2D6 and CYP3A4 activity was decreased by 40.70 %, 45.88 %, 62.68 % and 37.41 %, 42.58 % and 67.86 % at 1, 10 and 100 µM eugenol level respectively. The IC₅₀ value of eugenol for CYP2D6 and CYP3A4 was calculated as 11.09 ± 3.49 µM and 13.48 ± 3.86 µM respectively. Potential herb-drug interactions was noted when eugenol is administered simultaneously with medications metabolized by these enzymes, most notably CYP2C9, CYP2D6 and CYP3A4.

Pterostilbene (PTS) is a naturally occurring phytoalexin. PTS displays limited water solubility, which consequently results in its diminished oral bioavailability. Therefore, a ternary inclusion complex (TIC) of PTS with β-cyclodextrin (βCD) in the presence of ternary substance Pluronic^® F-127 (PLF) was prepared using microwave technology. The PTS-TIC was characterized by dissolution performance. Further, the prepared TIC was characterized by DSC, FTIR, NMR, XRD, and SEM analysis. Additionally, the antioxidant activity of PTS and PTS-TIC was also evaluated. Phase-solubility studies revealed that PTS’s solubility in water was increased by 6.72 times when βCD/PLF was present. In comparison with PTS, prepared PTS-TIC produced a considerable improvement in PTS release. After 1 h, 74.03 ± 4.47% of PTS was released from PTS-TIC. Outcomes of DSC, FTIR, NMR, XRD, and SEM analysis revealed that the PTS was enclosed in the βCD cavity. In terms of antioxidant properties, the PTS-TIC formulation demonstrated superior activity compared to PTS, possibly attributed to the improved solubility of PTS resulting from the formation of TIC using microwave technology. It was concluded that microwave technology proved to be an extremely beneficial means of interacting PTS with βCD. In addition to increasing the solubility of PTS, the findings are also expected to improve its bioavailability by increasing its solubility. As a result, this study could provide insight into potential methods for enhancing the solubility of polyphenolic substances like PTS.

Sinapic acid (SA) is a bioactive phenolic acid; its diverse properties are its anti-inflammatory, antioxidant, anticancer, and antibacterial activities. The bioactive compound SA is poorly soluble in water. Our goal was to formulate SA-transethosomes using thin-film hydration. The prepared formulations were examined for various parameters. In addition, the optimized formulation was evaluated for surface morphology, in-vitro penetration studies across the Strat M^®, and its antioxidant activity. The optimized formulation (F5) exhibited 74.36% entrapment efficacy. The vesicle size, zeta potential, and polydispersity index were found to be 111.67 nm, −7.253 mV, and 0.240, respectively. The surface morphology showed smooth and spherical vesicles of SA-transethosomes. In addition, the prepared SA-transethosomes exhibited enhanced antioxidant activity. The SA-transethosomes demonstrated considerably greater penetration across the Strat M^® membrane during the study. The flux of SA and SA-transethosomes through the Strat M^® membrane was 1.03 ± 0.07 µg/cm²/h and 2.93 ± 0.16 µg/cm²/h. The enhancement ratio of SA-transethosomes was 2.86 ± 0.35 compared to the control. The SA-transethosomes are flexible nano-sized vesicles and are able to penetrate the entrapped drug in a higher concentration. Hence, it was concluded that SA-transethosome-based approaches have the potential to be useful for accentuating the penetrability of SA across the skin.