pH-Sensitive micelles self-assembled from amphiphilic copolymer brush for delivery of poorly water-soluble drugs.
A novel pH-sensitive amphiphilic copolymer brush poly(methyl methacrylate-co-methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate) [P(MMA-co-MAA)-b-PPEGMA] was defined and synthesized by atom transfer radical polymerization (ATRP) technique. The molecular structures and characteristics of this copolymer and its precursors were confirmed by (1)H NMR, FT-IR, and GPC. The CMC of P(MMA-co-MAA)-b-PPEGMA in aqueous medium was determined to be 1-4 mg/L. This copolymer could self-assemble into micelles in aqueous solution with an average size of 120-250 nm determined by DLS. The morphologies of the micelles were found to be spherical by SEM and TEM. Ibuprofen (IBU), a poorly water-soluble drug, was selected as the model drug and wrapped into the core of micelles via dialysis method. Drug entrapment efficiency reached to 90%. The in vitro release behavior of IBU from these micelles was pH-dependent. The cumulative release percent of IBU was less than 20% of the initial drug content in simulated gastric fluid (SGF, pH 1.2) over 12 h, but 90% was released in simulated intestinal fluid (SIF, pH 7.4) within 6 h. The release profiles showed that the P(MMA-co-MAA)-b-PPEGMA micelles could inhibit the premature burst drug release under the intestinal conditions. All the results indicate that the P(MMA-co-MAA)-b-PPEGMA micelle may be a potential oral drug delivery carrier for poorly water-soluble drugs.
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, People's Republic of China.
You Qiang
YQ
Yang
Ling Shan
LS
Zheng
Xin Dong
XD
Guo
Yu
Y
Qian
Li Juan
LJ
Zhang
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D008823:Micelles; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors; D014867:Water / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008689:Methacrylates; D008823:Micelles; D011109:Polymethacrylic Acids; C528061:poly(poly(ethylene glycol)methacrylate); D014867:Water; C038300:methylmethacrylate-methacrylic acid copolymer; D011092:Polyethylene Glycols; D007052:Ibuprofen