Application of the lithium and magnesium initiators for the synthesis of glycolide, lactide, and epsilon-caprolactone copolymers biocompatible with brain tissue.

The subject of this work is new method of the synthesis of biodegradable copolymers compatible with brain tissue. Copolymerization of glycolide with lactide was conducted in solution or in bulk in the presence of LiBu, LiAcac, MgBu(2), Mg(acac)(2) as initiators. In all cases, copolymers with molecular weight of 20000-40000 were obtained, which enables to use them as drug carriers. During the reactions of copolymer chain growth, the intermolecular transesterification occurs, changing the distribution of comonomeric units in copolymer chain. Magnesium initiators showed a lower contribution to transesterification in comparison with lithium and calcium compounds. The copolymerization of glycolide with epsilon-caprolactone using magnesium compounds as initiators was also described. The random glycolide/epsilon-caprolactone copolymer (10/90) obtained with MgBu(2) was used in in vivo study in the forms of microspheres and foils. Complete degradation of microspheres during 6 weeks was observed after the implantation to brain tissue. All implanted copolymers are compatible with brain tissue.