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

• Main Authors: Nawaz, A. (Author), Wong, T.W (Author)
• Format: Article
• Language: English
• Published: Elsevier B.V. 2018
• Subjects: Administration, Cutaneous; animal experiment; antineoplastic activity; antineoplastic agent; area under the curve; Article; carboxymethyl-chitosan; Cell Line, Tumor; cell membrane; cell viability; chemistry; chitosan; Chitosan; chitosan carboxymethyl 5 fluorouracil folate conjugate; chitosan derivative; controlled study; cutaneous drug administration; drug bioavailability; drug delivery system; Drug Delivery Systems; drug effect; drug release; drug retention; fluorouracil; Fluorouracil; fluorouracil derivative; folic acid; Folic Acid; human; Humans; in vitro study; in vivo study; lipid raft; male; maximum plasma concentration; melanoma; Melanoma; melanoma cell; membrane microdomain; Membrane Microdomains; microwave irradiation; microwave radiation; Microwaves; nanoparticle; Nanoparticles; nonhuman; particle size; pathology; pharmacokinetic parameters; plasma concentration-time curve; priority journal; rat; skin; Skin; skin absorption; Skin Absorption; skin cell; Skin Neoplasms; skin tumor; SK-MEL-28 cell line; tumor cell line; unclassified drug; zeta potential
• Online Access: View Fulltext in Publisher; View in Scopus

 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. © 2018 The Authors