PH- and redox-responsive poly(ethylene glycol) and cholesterol-conjugated poly(amido amine)s based micelles for controlled drug delivery

An optimized condition is identified to prepare linear poly(amido amine)s via Michael Addition polymerization of trifunctional amine, 4-(aminomethyl) piperidine (AMPD), with an equimolar diacrylamide, N,N-cystaminebis(acrylamide) (BAC). Poly(ethylene glycol) (PEG) and cholesterol (CE) are conjugated to linear poly(BAC-AMPD) through the reactions with the secondary amino groups in the backbone, respectively, to form poly(BAC-AMPD)-g-PEG-g-CE. The chemical structures of poly(BAC-AMPD) and poly(BAC-AMPD)-g-PEG-g-CE are characterized using NMR and gel permeation chromatography (GPC). Transmission electron microscopy (TEM), dynamic light scattering (DLS) and ¹H NMR results show that micelles with PEG shells and hydrophobic cores composed of poly(BAC-AMPD) and CE are formed via self-assembly of poly(BAC-AMPD)-g-PEG-g-CE in aqueous solution, and the micelles of poly(BAC-AMPD)-g-PEG-g-CE can be degraded by the presence of L-dithiothreitol and show a limited cytotoxicity in vitro. The anti-cancer drug, doxorubicin (DOX), can be loaded into the micelles. The DOX loaded micelles of poly(BAC-AMPD)-g-PEG-g-CE show pH- and redox-responsive drug release and redox-induced formation of aggregates, and it is shown that the DOX loaded micelles can deliver DOX into cells and show a higher efficacy in killing cancer cells than free drug. Novel doxorubicin (DOX) loaded pH- and redox-responsive cholesterol conjugated poly(amido amine)s micelles are prepared and show a higher efficacy in killing cancer cells than the free drug. The micelles with poly(ethylene glycol) shells and cores composed of cholesterol and poly(amido amine)s can encapsulate DOX. DOX loaded micelles can enter cancer cells and form redox-induced aggregates, so more DOX can be delivered to the nuclei of cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.