Synthesis and characterization of amphiphilic star-shaped copolymers based on -cyclodextrin for micelles drug delivery

Purpose: A series of -CD amphiphilic star-shaped copolymers with exceptional characteristics were synthesized and their potential as carriers for micelles drug delivery was investigated.Methods: A series of amphiphilic copolymers based on -CD were synthesized by introducing poly (acrylic acid)-co-poly(methyl methacrylate)-poly (vinyl pyrrolidone) or poly (acrylic acid)-co-poly(methyl methacrylate)-co-poly(monoacylated--CD)-poly (vinyl pyrrolidone) blocks to the primary hydroxyl group positions of -CD. The micellization behavior of the copolymers, the synthesis conditions, characteristics, drug release in vitro and tissue distribution of vinpocetine (VP) micelles in vivo were investigated.Results: Around 60 types of -CD amphiphilic star-shaped copolymers were successfully synthesized and the critical micelle concentration ranged from 9.80x10(-4) to 5.24x10(-2)g/L. The particle size, drug loading and entrapment efficiency of VP-loaded -CD-P-4 micelles prepared with optimal formulation were about 65nm, 21.440.14%, and 49.05 +/- 0.36%, respectively. The particles had good sphericity. The cumulative release rates at 72h of VP-loaded -CD-P-4 micelles in pH 1.0, pH 4.5, pH 6.5, or pH 7.4 media were 93%, 69%, 49%, and 43%, respectively. And, the lung targeting efficiency of VP-loaded -CD-P-4 micelles was 8.98 times higher than that of VP injection.Conclusion: The VP-loaded -CD-P-4 micelles exhibited controlled-release property, pH-induced feature and lung targeting capacity compared with VP injection, suggesting that the -CD-P-4 copolymers are an excellent candidate for micelles drug delivery.