pH-responsive nanosized-micelles based on poly(monomethylitaconate)-co-poly(dimethylaminoethyl methacrylate) and cholesterol side chains effect on pH change-induced release of piroxicam

Novel double hydrophilic poly(monomethylitaconate)-co-poly(N,N-dimethylaminoethyl methacrylate) (PMMI-co-PDMAEMA) synthesized via free radical polymerization of corresponding monomers with defined molar ratios in the presence of K₂S₂O₈ as an initiator in an aqueous solution. The resulting copolymer was subsequently converted to a cholesterol conjugate (PMMICholC₆-co-PDMAEMA) by esterification reaction with 6-cholesteryl-1-hexanol (CholC₆). Two copolymers self-assembled into micelles by simply adjusting the solution pH at room temperature. The non-conjugated polymer had a sharp transition at pH 5. TEM and DLS studies showed that both micelles were spherical in shape with a mean diameter around 85 and 26 nm, respectively. Piroxicam (PX) as a hydrophobic model drug was encapsulated into micelles. The results indicated that PMMICholC₆-co-PDMAEMA micelles were able to load more amounts of drug than PMMI-co-PDMAEMA micelles which could be attributed to the strong hydrophobic interactions of cholesterol molecules in the core. In vitro release studies demonstrated that PX release from PMMI-co-PDMAEMA micelles was significantly fast at physiological pH compared with mildly acidic pH 4.5. However, at pH 4.5, PMMICholC₆-co-PDMAEMA micelles, with core-shell-corona structure, released loaded drug molecules faster than pH 7.4 which contained a relatively steady drug release profile. In summary, cholesterol-modified micelles could be introduced as stable and effective pH responsive nanocarriers to make a promising system for enhancing the efficacy of hydrophobic drugs in cancer cells for improved cancer therapy.