Stabilized polymeric micelles by electrostatic interactions for drug delivery system.
Methoxy poly(ethylene glycol)-block-oligo(l-aspartic acid)-block-poly(epsilon-caprolactone) with four aspartic acid groups was synthesized with a molecular weight and M(w)/M(n) of 8930 and 1.22. Polymeric micelles were formed by dialysis and stabilized by electrostatic interactions between the carboxylic acid groups and calcium cations. The critical micelle concentration of mPEG-Asp-PCL was determined to be 0.078 mg/mL. At 0.02 mg/mL, the dissociation of micelles without ionic stabilization formed an opaque, phase-separated solution, while the stabilized micelles under the same conditions showed structural stability through ionic stabilization. The paclitaxel-loading and efficiency were 8.7% and 47.6%, respectively, and the drug loading increased the mean diameter from 73.0 nm to 87 nm, which was increased further to 96 nm after ionic fixation. Rapid releases of approximately 65% of the encapsulated paclitaxel from a non-stabilized micelle and 45% from a stabilized micelle were observed in the first 24h at pH 7.4 in a PBS solution containing 0.1 wt% Tween 80. The stabilized micelles then showed a sustained, slow release pattern over a couple of weeks, while the profile from the non-stabilized micelles reached a plateau at approximately 75% after 50h. The enhanced micelle stability independent of concentration through ionic stabilization opens a way for preparing long circulating delivery systems encapsulating water-insoluble drugs.
Cha
Eui-Joon
EJ
Research Institute of Advanced Materials (RIAM), Department of Materials Science, Seoul National University, San 56-1, Sillim, Gwanak, Seoul 151-744, Republic of Korea.
Kim
Ju Eun
JE
Ahn
Cheol-Hee
CH
D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D008823:Micelles; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D055672:Static Electricity
D008823:Micelles; D011108:Polymers