Chitosan-Carboxymethyl-5-Fluorouracil-Folate Conjugate Particles: Microwave Modulated Uptake by Skin and Melanoma Cells

Abstract

5-Fluorouracil delivery profiles in the form of chitosan-folate submicron particles through skin and melanoma cells in vitro were examined using microwaves as the penetration enhancer. The in vivo pharmacokinetic profile of 5-fluorouracil was also determined. Chitosan-carboxymethyl-5-fluorouracil-folate conjugate was synthesized and processed into submicron particles by spray-drying technique. The size, zeta potential, morphology, drug content, and drug release, as well as skin permeation and retention, pharmacokinetics, in vitro SKMEL-28 melanoma cell line cytotoxicity, and intracellular trafficking profiles of drug/particles, were examined as a function of skin/melanoma cell treatment by microwaves at 2,450 MHz for 5 + 5 minutes. The level of skin drug/particle retention in vitro and in vivo increased in skin treated by microwaves. This was facilitated by the drug conjugating to chitosan and microwaves fluidizing both the protein and lipid domains of epidermis and dermis. The uptake of chitosan-folate particles by melanoma cells was mediated via lipid raft route. It was promoted by microwaves, which fluidized the lipid and protein regimes of the cell membrane, and this increased drug cytotoxicity. In vivo pharmacokinetic study indicated skin treatment by microwave-enhanced drug retention but not permeation. The combination of microwaves and submicron particles synergized skin drug retention and intracellular drug delivery.

Cellulose Nanocrystals/Chitosan-Based Nanosystems: Synthesis, Characterization, and Cellular Uptake on Breast Cancer Cells

“…Worth noting here is the absence of the absorption bands at 1686 cm −1 (carboxyl moiety of FA [38]) and 2018 cm −1 (isothiocyanate moiety (N=C=S) of the FITC [39]), together with the appearance of the absorption band (ca. 1650 cm −1 ) assigned to the amide thioamide bonds [42], that confirm the covalent link between CS and FA [43], and CS and FITC [44], respectively, in agreement with data reported elsewhere [45]. The morphology and size of the CNCs nanosystems functionalized with the FITC derivative were assessed by STEM (Figure 3).…”

Chitosan nanoparticles for enhancing drugs and cosmetic components penetration through the skin

“…CT NPs have been employed for skin drug delivery to treat local disorders such as skin malignant melanoma [14] and infection [15] and for systemic complications such as diabetes [16] and hypertension [17]. Although various studies have been conducted on CT for skin delivery, there is little conclusive evidence that demonstrate that polysaccharide NPs can penetrate epidermis and dermis [18]. Further, the mechanism of polysaccharide NPs in promoting transdermal drug transport is not known.…”

Olive Oil Based Methotrexate Loaded Topical Nanoemulsion Gel for the Treatment of Imiquimod Induced Psoriasis-like Skin Inflammation in an Animal Model

“…Skin excision into small pieces was performed meticulously, followed by saline washing and tap drying. The skin was swirled in distilled water overnight to remove methotrexate, then filtered and analyzed using HPLC to determine the residual drug concentration [ 40 ].…”