Synthesis and application of poly(ethylene glycol)-cholesterol (Chol-PEGm) conjugates in physicochemical...

Vesicles possessing poly(ethylene glycol) (PEG) chains on their surface have been described as a blood-persistent drug delivery system with potential applications for intravenous drug administration. In this research with different molecular weights (400-10,000g/mol) of PEG, a series of Chol-PEG(m) conjugates were generated by the DCC (N,N'-dicyclohexylcarbodiimide, DCC)/(4-dimethylaminopyridine, 4-DMAP) esterification method, and confirmed by FT-IR and (1)H NMR spectrum. Then their properties in aqueous solution were studied by electron microscopy images, associative behavioral and systematic tensiometric studies over a wide concentration range. In order to elucidate the application of this Chol-PEG(m) in vesicles, conventional nonionic surfactant vesicles (niosomes) composed of span 60 and cholesterol were prepared and the influence of various hydrophilic chains of the Chol-PEG(m) conjugates was investigated. Results indicated that all the niosomes prepared, with or without Chol-PEG(m) composition were similar in micrograph with diameter between 120 nm and 180 nm. The fixed aqueous layer thickness (FALT) around niosomes increased as Chol-PEG(m) chain length increase, particularly in the Chol-PEG(10,000) modified niosomes with 9.33+/-0.67 nm. In vitro release experiments indicated that release rate of nimodipine from Chol-PEG(m) modified niosomes was enhanced. Chol-PEG(m) modified niosomes showed greater accumulative release than that of plain niosomes over a period of 24 h. These studies have shed some light on the suitability of Chol-PEG(m) containing niosome preparation.