Application of the lithium and magnesium initiators for the synthesis of glycolide, lactide, and ϵ‐caprolactone copolymers biocompatible with brain tissue

Abstract

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.

Copolymerization and terpolymerization of glycolide with lactones by dimethyl(salicylaldiminato)aluminum compounds

“…The resonances were assigned according to the literature ( Figure 5). 19 The chemical composition of the terpolymers was determined through the ratio The effect of the catalyst was studied for equimolar amount of the three monomers (Table IV, runs 13,16,17). The calculation of average glycolidyl, L GG , lactidyl, L LL , and caproyl blocks, L Cap , as well as the determination of contribution of sequences formed by transesterification of the second mode, was also obtained from the 1 H NMR analysis by using literature formulas.…”

“…[1][2][3][4] In particular, PGA is a very promising polymer, but it is hydrolytically unstable, hardly processable, and too brittle for many applications. [9][10][11][12][13][14][15][16] In turn, the incorporation of Cap into PLGA chains, resulting in poly[(glycolide-co-lactide-co-(e-caprolactone)] (PGLC) terpolymer, [17][18][19][20] has been also found to be beneficial for the application of these materials in drug delivery and tissue engineering. The use of LA as comonomer represented the common choice and produced the well-known poly(lactide-co-glycolide) (PLGA) copolymers, by far the most widely used biodegradable materials in packaging, textile and surgical fibers, drug delivery systems, and stem cell scaffoldings.…”

“…[5][6][7][8] On the other hand, Cap has been less used as comonomer, although it could impart different hydrophilicity, elasticity, solubility, crystallization, and degradation rates. In the case of PGCAs, initiators based on Fe, Al, Zn, 9 Zr, 11,14,19 Ca, 12 Mg, 16 and Bi [25][26][27] were reported. [9][10][11][12][13][14][15][16] In turn, the incorporation of Cap into PLGA chains, resulting in poly[(glycolide-co-lactide-co-(e-caprolactone)] (PGLC) terpolymer, [17][18][19][20] has been also found to be beneficial for the application of these materials in drug delivery and tissue engineering.…”

The Influence of Chain Microstructure of Biodegradable Copolyesters Obtained with Low-Toxic Zirconium Initiator toIn VitroBiocompatibility

“…The stannous ion can generate reactive oxygen species capable to damage cellular DNA [33]. Because of these facts, several attempts were undertaken to synthesize biodegradable polymers with the use of initiators more compatible with human organism as lithium, magnesium, iron, zinc, or zirconium compounds [29, 34–36]. Zirconium compounds were found to be tens times less toxic than analogous tin compounds.…”

“…Selection of the biodegradable polyesters materials for chondrocytes culture was done on the basis of degradation process investigations presented in our previous papers [36, 43–48]. …”