Injectable nanospheres from a novel multiblock copolymer: Cytocompatibility, degradation and in vitro release studies

Abstract

The aim was to develop and characterize nanospheres made from a newly synthesized poly (D, L-lactide-co-ethyleneglycol) (-PLA-PEG-PLA-)_n multi-block copolymer. Nanospheres were prepared under optimized conditions of modified emulsion-solvent evaporation technique in a continuous flow process using rhodamine B as a drug model. They were characterized for size distribution, zeta (ζ) potential, porosity and morphology. Drug loading and yield were also determined. In vitro degradation studies of the copolymer were conducted in phosphate buffer (pH 7.4) at 37°C. The cytotoxic properties of the polymer and vector were analysed by dimethylthiazoldiphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays on the B16 mouse cell line. Release of rhodamine B from the nanospheres was assayed in vitro using a dialysis bag in isotonic phosphate buffer (pH 7.4) at 37°C. Spherical and non-porous nanospheres with mean size less than 800nm could be prepared. The (ζ) potential was neutral. The average yield was approximately 70% with 7% rhodamine loading. A total of 50% of the multiblock underwent initial degradation after 4 weeks, while degradation was complete after 16 weeks. Cellular proliferation was not inhibited as no cytotoxicity was observed with the copolymers and nanospheres. Rhodamine B was released in a stepwise pattern. The initial burst was 20%, and release was prolonged thereafter for 29 days. Thus, injectable nanospheres with prolonged rhodamine B release have been designed and characterized as a potential drug-delivery system.

Key Words:

• nanosphere
• poly (D, L-lactide-co-ethylene glycol) multiblock copolymer
• cytocompatibility
• degradation
• rhodamine B