pH-sensitive nanoparticles prepared from amphiphilic and biodegradable methoxy poly(ethylene glycol)-block-(polycaprolactone-graft-poly(methacrylic acid)) for oral drug delivery

A novel pH-sensitive, amphiphilic and biodegradable copolymer brush, methoxy poly(ethylene glycol)-block-(polycaprolactone-graft-poly(methacrylic acid)) (mPEG-b-(PCL-g-PMAA)), was developed for NPs for the oral delivery of hydrophobic drugs. The copolymer brush was synthesized by combining ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP), followed by selective hydrolysis. The structure and composition of the copolymer and its precursors were characterized by H-1-NMR, FT-IR and GPC. The critical micelle concentrations (CMC) of mPEG-b-(PCL-g-PMAA) in aqueous medium were determined to be 6.8 x 10(-4) and 9.6 x 10(-4) mg mL(-1). The copolymer could self-assemble into NPs in aqueous solution with an average size of 104-129 nm, determined by DLS. The morphology of the NPs was spherical, as observed by TEM. The zeta potentials of the NPs were about -25 mV, measured by zeta potential measurements. Ibuprofen (IBU), a poorly water-soluble drug, was chosen as the model drug and encapsulated into the core of the NPs via a nano-precipitation method. The drug loading content (DLC) of the NPs prepared from mPEG-b-(PCL-g-PMAA) reached about 13%, with a drug loading efficiency (DLE) of above 75%. The in vitro release behavior of IBU from the NPs was pH-dependent. Typically, at pH 3.0 (0.01 M), the cumulative release percentage of IBU was about 40% over 12 h, whereas at pH 7.4 (0.01 M), more than 95% was released within 12 h for NPs prepared from mPEG(113)-b-(PCL91-g-PMAA(155)). The MTT assay indicated that blank NPs prepared from mPEG-b-(PCL-g-PMAA) did not show significant toxicity against NCL-H460 cells. These results indicated that this new type of pH-dependent polymeric NPs prepared from mPEG-b-(PCL-g-PMAA) has great potential to be used as a drug carrier for the oral administration of hydrophobic drugs.