Luteinizing-hormone-releasing-hormone-containing biodegradable polymer micelles for enhanced intracellular drug delivery.

A biodegradable triblock copolymer, poly(ethylene oxide)-block-poly(allyl glycidyl ether)-block-poly(dl-lactide) (mPEG-b-PAGE-b-PLA), with allyl groups on its middle block was designed and synthesized through anionic polymerization of allyl glycidyl ether (AGE) with PEG monomethyl ether sodium salt as the macroinitiator and subsequent ring-opening polymerization of dl-lactide. Luteinizing hormone-releasing hormone (LHRH) was conjugated to the PAGE block through a linkage of -SCHCHC([double bond, length as m-dash]O)NH- between the allyl and LHRH residues. The LHRH content in the conjugate was ca. 25 wt%. Owing to the amphiphilic nature of the conjugate, it was self-assembled into micelles of 15-40 nm in diameter and with the LHRH moieties in the hydrophilic corona of the micelles. Cellular uptake experiments were carried out using flow cytometry and confocal laser scanning microscopy (CLSM) with HeLa cells as LHRH-receptor overexpressing cells and HepG-2 cells as normal cells. HeLa cells displayed more cellular uptake of the LHRH-micelles than the normal cells. In vivo biodistribution of the LHRH-containing micelles and LHRH-free micelles was studied using a CRI Maestro™ imaging system. Preferred accumulation in tumor sites of LHRH-containing micelles was observed at 24 hours post injection. Therefore, LHRH-conjugated amphiphilic copolymers might be used as a potential drug delivery system for the treatment of LHRH receptor overexpressing carcinoma.