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Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy.

ABSTRACT: Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of -27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ± 6.0 and 79.43 ± 12.43 µg/cm²/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.

SUBMITTER: Md S

PROVIDER: S-EPMC8002493 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Retinol has been widely used as an anti-wrinkle active ingredient in cosmetic fields. However, the oxidation of retinol by air was one of the critical problems for application in the skincare field. In this study, Retinol-loaded lipid nanocarriers were prepared via the vacuum emulsification method to increase the stability of retinol vulnerable to air and optimized encapsulation conditions and to increase the penetration efficiency into skin. Optimizing the components of lipid nanocarriers, gradients of carbon chain C8-22 using various lipid species which made the amorphous structure and enough spaces to load retinol inside the capsules were estimated from the lower enthalpy change and peak shift in DSC analysis. The vacuum-assisted lipid nanocarriers (VLN) could help suppress oxidation, which could have advantages to increase the thermal stability of retinol. The retinol-loaded VLN (VLN-ROL) had narrow size distribution under 0.3 PDI value, under 200 nm scaled particle size, and fully negative surface charge of about -50 mV for the electrostatic repulsion to avoid aggregation phenomenon among the lipid nanoparticles. It maintained 90% or more retinol concentration after 4 weeks of storage at 25, 40 and 50 °C and kept stable. The VLN-ROL-containing cream showed improved penetration efficiency applied to porcine skins compared to the commercial retinol 10S from BASF. The total amount of retinol into the skin of VLN-ROL (0.1% of retinol) was enhanced by about 2.2-fold (2.86 ± 0.23 μg) higher than that in 0.1% of bare retinol (about 1.29 ± 0.09 μg). In addition, applied on a 3D Human skin model, the epidermal thickness and the relative percentage of dermal collagen area effectively increased compared to the control and retinol, respectively. Additionally, the level of secreted IL-1α was lower and epidermal damage was weaker than commercial product A. This retinol-loaded lipid nanocarrier could be a potentially superior material for cosmetics and biomedical research.

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Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy.

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