Lactide property

Polylactide is the generaUy accepted term for highly polymeric poly(lactic acid)s. Such polymers are usuaUy produced by polymerization of dilactide the polymerization of lactic acid as such does not produce high molecular weight polymers. The polymers produced from the enantiomeric lactides are highly crystalline, whereas those from the meso lactide are generaUy amorphous. UsuaUy dilactide from L-lactic acid is preferred as a polymerization feedstock because of the avaUabUity of L-lactic acid by fermentation and for the desirable properties of the polymers for various appUcations (1,25). 

Poly(lactide-coglycolide). Mixtures of lactide and glycolide monomers have been copolymerised in an effort to extend the range of polymer properties and rates of in vivo absorption. Poly(lactide- (9-glycolide) polymers undergo a simple hydrolysis degradation mechanism, which is sensitive to both pH and the presence of ensymes (32). 

Copolymers of S-caprolactone and L-lactide are elastomeric when prepared from 25% S-caprolactone and 75% L-lactide, and rigid when prepared from 10% S-caprolactone and 90% L-lactide (47). Blends of poly-DL-lactide and polycaprolactone polymers are another way to achieve unique elastomeric properties. Copolymers of S-caprolactone and glycoHde have been evaluated in fiber form as potential absorbable sutures. Strong, flexible monofilaments have been produced which maintain 11—37% of initial tensile strength after two weeks in vivo (48). 

Lactic acid and levulinic acid are two key intermediates prepared from carbohydrates [7]. Lipinsky [7] compared the properties of the lactide copolymers [130] obtained from lactic acid with those of polystyrene and polyvinyl chloride (see Scheme 4 and Table 5) and showed that the lactide polymer can effectively replace the synthetics if the cost of production of lactic acid is made viable. Poly(lactic acid) and poly(l-lactide) have been shown to be good candidates for biodegradeable biomaterials. Tsuji [131] and Kaspercejk [132] have recently reported studies concerning their microstructure and morphology. 

Table 5 Comparison of Properties of Lactide Polymers with Polystyrene and Poly(vinyl chloride) ...

Polymer/Property Polystyrene 95/5 Lactide/Caprolactone 95/15 Lactide/Caprolactone Flexible PVC... 

Kulinski, Z. and Piorkowska, E. 2005. Crystallization, structure and properties of plasticized poly(L-lactide). Polymer 46 10290-10300. 

Lannace, S., Ambrosio, L., Huang, S.J. and Nicolais, L. 1994. Poly(3- hydroxybutyrate)-co-(3-hydroxyvalerate)/poly-l-lactide blends thermal and mechanical properties. Journal of Applied Polymer Science 54 1525-35. 

Lactide/glycolide polymers have been investigated for delivery of agents in applications outside the pharmaceutical field. For example, the microbiocidal properties of chlorine dioxide disinfectants have been improved by formulating a long-acting chlorine dioxide system based on lactide/glycolide copolymers. Blends of microspheres based on 50 50 and 87 13 copolymers were developed to afford the release of chlorine dioxide over several months (114). 

Zhu, K. J., Xiangzhou, L., and Shilin, Y., Preparation and properties of D,L-lactide and ethylene oxide copolymer A modifying biodegradable polymeric material, J. Polym. Sei. Part C Polvm. Lett.. 24, 331-337, 1986. 

The solution to this problem has been to isolate the lactide and to polymerize this directly using a tin(ii) 2-(ethyl)hexanoate catalyst at temperatures between 140 and 160 °C. By controlling the amounts of water and lactic acid in the polymerization reactor the molecular weight of the polymer can be controlled. Since lactic acid exists as d and L-optical isomers, three lactides are produced, d, l and meso (Scheme 6.11). The properties of the final polymer do not depend simply on the molecular weight but vary significantly with the optical ratios of the lactides used. In order to get specific polymers for medical use the crude lactide mix is extensively recrystallized, to remove the meso isomer leaving the required D, L mix. This recrystallization process results in considerable waste, with only a small fraction of the lactide produced being used in the final polymerization step. Hence PLA has been too costly to use as a commodity polymer. 

Lactide (LA), the cyclic diester of lactic acid, has two stereogenic centers and hence exists as three stereoisomers L-lactide (S,S), D-lactide (R,R), and meso-lactide (R,S). In addition, rac-lactide, a commercially available racemic mixture of the (R,R) and (S,S) forms, is also frequently studied. PLA may exhibit several stereoregular architectures (in addition to the non-stereoregular atactic form), namely isotactic, syndiotactic, and heterotactic (Scheme 15). The purely isotactic form may be readily prepared from the ROP of L-LA (or D-LA), assuming that epimerization does not occur during ring opening. The physical properties, and hence medical uses, of the different stereoisomers of PLA and their copolymers vary widely and the reader is directed to several recent reviews for more information.736 740-743... 

These representative aliphatic polyesters are often used in copolymerized form in various combinations, for example, poly(lactide-co-glycolide) (PLGA) [66-68] and poly(lactide-co-caprolactone) [69-73], to improve degradation rates, mechanical properties, processability, and solubility by reducing crystallinity. Other monomers such as 1,4-dioxepan-5-one (DXO) [74—76], 1,4-dioxane-2-one [77], and trimethylene carbonate (TMC) [28] (Fig. 2) have also been used as comonomers to improve the hydrophobicity of the aliphatic polyesters as well as their degradability and mechanical properties. 

To provide for prolonged, site-specific delivery of NGF to the tissue in a convenient manner without affecting the properties of the conduit, biodegradable polymer microspheres of poly(L-lactide)co-glycolide... 

H. Tsuji, Y. Kawashima, H. Takikawa, S. Tanaka, Poly(L-lactide)/nano-structured carbon composites Conductivity, thermal properties, crystallization, and biodegradation., Polymer, vol. 48, pp. 4213-4225, 2007. 

Due to its stereogenic center, lactic acid exists in two enantiomeric forms (d- and L-lactic acid), leading to three different lactide stereoisomers (d-, l- and mesolactide). Depending on the relative amounts of the different stereoisomers in the final polyester, the crystallinity of the resulting PLA is heavily influenced and this way the properties of the polymer can be adjusted to satisfy the needs of different applications [18-20]. 

Schiff base ligands are a particularly suitable alternative in ROP of lactide because of their ease of preparation and the possibility to easily tunable steric and electronic properties. Chisholm and coworkers reported Schiff base-supported zinc amide and phenoxide complexes 51a, b (Fig. 10) [75], which catalyze the polymerization of L-lactide in benzene at room temperature yielding 90% conversion in 3 h for 51a and 72 h for 51b. The significant difference in reactivity between the catalysts can be taken from the rate of initiation, which is slower for 51a owing to presence of bulky 2,6-ferf-butylphenoxide leaving group. 

The mechanical properties of PLA rely on the stereochemistry of insertion of the lactide monomer into the PLA chain, and the process can be controlled by the catalyst used. Therefore, PLAs with desired microstructures (isotactic, heterotactic, and S3mdiotactic) can be derived from the rac- and W50-Iactide depending on the stereoselectivity of the metal catalysts in the course of the polymerization (Scheme 15) [66]. Fundamentally, two different polymerization mechanisms can be distinguished (1) chain-end control (depending on stereochemistry of the monomer), and (2) enantiomorphic site control (depending on chirality of the catalyst). In reality, stereocontrolled lactide polymerization can be achieved with a catalyst containing sterically encumbered active sites however, both chain-end and site control mechanisms may contribute to the overall stereocontrol [154]. Homonuclear decoupled NMR analysis is considered to be the most conclusive characterization technique to identify the PLA tacticity [155]. Homonuclear... 

---