Abstract
In the present study, polymeric micelles constituted of N-(2-hydroxypropyl)methacrylamide (HPMA) and methoxypoly(ethylene glycol) (mPEG)-based copolymer, mPEG-b-HPMA was studied for the delivery of an anticancer drug, doxorubicin (DOX) by physically loading the drug into its core. A series of mPEG-b-HPMA copolymers of different molecular weights (MWs, ∼4000−25,000 Da) by using various initiator: monomer feed ratios (1:25/75/125/175) were synthesized by radical polymerization technique. The DOX-loaded micelles were prepared at different drug to polymer ratios by thin film hydration method. Block copolymers were structurally characterized by gel permeation chromatography (GPC), 1H-NMR spectroscopy, fourier transform infrared spectroscopy (FTIR), and critical micelles concentration studies. The DLS and SEM studies indicated that the micelles were spherical with diameters ∼20−100 nm. The DOX-loaded mPEG-b-HPMA micelles, P6-M1, prepared by the polymer synthesized using initiator: monomer feed ratios of 1:175 and at polymer to drug ratios of 10:1 exhibited low particle sizes (∼46.8 nm), highest drug loading and encapsulation efficiencies (5.6 %, and 63.3 %, respectively) compared to the other tested formulations. Confocal microscopy study indicated that the P6-M1 was taken up by breast cancer cell lines, 4T1, MCF-7, and MDA-MB-231in a time-dependent manner. P6-M1 displayed lower half maximal inhibitory concentration (IC50) compared to free drug in all tested treatment durations compared to free DOX. P6-M1 was safe in hemolysis studies with sustained DOX residence in circulation compared to free DOX. The results indicated that mPEG-b-HPMA could be utilized to load DOX effectively, and the optimized nano-micelles, P6-M1 could serve as a promising nanomedicine to treat breast cancer.
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