Triggering the fast release of drugs from crosslinked micelles in an acidic environment

Crosslinked micelles with pH responsive features were obtained by adjusting the rate of the addition of crosslinker to the micellar system. A block copolymer, block poly(poly(ethylene glycol) methyl ether methacrylate)-block-poly(methyl methacrylate-co-poly(3-isopropenyl-alpha,alpha-dimethylbenzyl isocyanate)) (PPEGMEMA-b-P(MMA-co-TMI)), was prepared via the RAFT process and self-assembled into micelles. Addition of 1,8-diaminooctane leads to crosslinking of the micelles, but also to excess amine groups that can respond to changes of pH value. At low pH value the micelle swelled in the media. The drug, albendazole (ABZ), was encapsulated tightly at pH 7, but released suddenly at pH 5. Cell experiments using OVCAR-3 cell lines show the efficient uptake of these nanoparticles and the fast release of the drug. In contrast to a non-responsive micelle system, the drug was released within 10 min once the nanoparticles have been taken up by the cell, a process that has been promoted by the acidic environment of the endosomes and lyzosomes.