L lactide

Polymer—polymer iacompatibiHty encapsulation processes can be carried out ia aqueous or nonaqueous media, but thus far have primarily been carried out ia organic media. Core materials encapsulated tend to be polar soHds with a finite degree of water solubiHty. EthylceUulose historically has been the sheU material used. Biodegradable sheU materials such as poly(D,L-lactide) and lactide—glycoHde copolymers have received much attention. In these latter cases, the object has been to produce biodegradable capsules that carry proteias or polypeptides. Such capsules tend to be below 100 p.m ia diameter and are for oral or parenteral administration (9). 

The actual time required for poly-L-lactide implants to be completely absorbed is relatively long, and depends on polymer purity, processing conditions, implant site, and physical dimensions of the implant. For instance, 50—90 mg samples of radiolabeled poly-DL-lactide implanted in the abdominal walls of rats had an absorption time of 1.5 years with metaboHsm resulting primarily from respiratory excretion (24). In contrast, pure poly-L-lactide bone plates attached to sheep femora showed mechanical deterioration, but Httie evidence of significant mass loss even after four years (25). 

The crystallinity of poly(lactide- (9-glycoHde) samples has been studied (36). These copolymers are amorphous between the compositional range of 25—70 mol % glycoHde. Pure polyglycoHde was found to be about 50% crystalline whereas pure poly-L-lactide was about 37% crystalline. An amorphous poly(L-lactide-i (9-glycoHde) copolymer is used in surgical cHps and staples (37). The preferred composition chosen for manufacture of cHps and staples is the 70/30 L-lactide/glycoHde copolymer. 

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). 

Braided Synthetic Absorbable Sutures. Suture manufacturers have searched for many years to find a synthetic alternative to surgical gut. The first successful attempt to make a synthetic absorbable suture was the invention of polylactic acid [26023-30-3] suture (15). The polymer was made by the ring-opening polymerization of L-lactide [95-96-5] (1), the cycUc dimer of L-lactic acid. 

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. 

Polycondensation At room temperature, 0.4% mass of Sn(II) chloride dihydrate (SnCl2-2H20) and 0.4% mass of p-toluenesulfonic acid monohydrate (p-TSA) are introduced into the mixture. The mixture is heated to 180°C under mechanical stirring. The pressure is reduced stepwise to reach 13 mbar, and file reaction is continued for 20 h. The reaction system becomes gradually viscous, and a small amount of L-lactide is formed and refluxed through the reflux condenser. At file end of the reaction, the flask is cooled down, file product is dissolved in chloroform and subsequently precipitated into diethyl ether. The resulting white fibrous solids are filtered and dried under vacuum (average yield 67%). 

Coordination numbers ranging from five to seven were observed, and they appeared to be controlled by the steric bulk of the supporting amidinate and coligands. Complexes 2-5 and 7 were found to be active catalysts for the pol3uneiization of D,L-lactide (e.g., with 2 and added benzyl alcohol, 1000 equiv of D,L-lactide were polymerized at room temperature in <1 h). The neutral complexes 2, 5, and 7 were more effective than the anionic complexes 3 and 4. ... 

Polymerization of D,L-lactide to polylactide was also achieved using monomeric tin(ll) amidinates (cf. Schemes 48 and and the mono... 

Bandyopadhyay, S., Chen, R. and Giannelis, E.P. 1999. Biodegradable organic-inorganic hybrids based on poly(L-lactide). polymer material science engineering 81 159-160. 

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. 

Paul, M., Alexandre, M., Degee, P., Henrist, C., Rulmont, A., and Dubois, P. 2002. New nanocomposite materials based on plasticized poly(L -lactide) and organo-modified montmorillonites thermal and morphological study. Polymer 44 443-450. 

Zhenyang, Y., Jingbo, Y., Shifeng, Y., Yongtao, X., Jia, M. and Xuesi, G. 2007. Biodegradable poly(L-lactide)/poly(3-caprolactone)-modified montmorillonite nanocomposites Preparation and characterization. Polymer 48 6439-6447. 

Recently, Cohn and Salomon synthesized and characterized a series of PLCL thermoplastic bioelastomers by two-step synthesis procedure. First, ring-opening polymerization of L-lactide initiated by the hydroxyl terminal groups of the PCL chain. Second, chain extension polymerization of these PLA-PCL-PLA triblocks initiated by the hexamethylene diisocyanate (HDl). 

SCHEME 8.8 Synthesis of statistical poly(trimethylene carbonate-co-D,L-lactide) copolymers. 

Pego AP, Siebum SB, Luyn MJAV, et al. Preparation of degradable porous structures based on 1,3-trimethylene carbonate and D,L-lactide(co)polymers for heart tissue engineering. Tissue Eng, 2003, 9, 981 994. 

Pego AP, Luyn MJAV, Brouwer LA, et al. In vivo behaviour of poly (1,3-trimethylene carbonate) and copolymers of 1,3-trimethylene carbonate with D,L-lactide or e-caprolactone Degradation and tissue response. J Biomed Mater Res, 2003, 67A, 1044—1054. 

Table 1 provides a summary of the glass transition temperatures of several lactide/glycolide polymers. Tg values range from about 40 to 65°C. Poly(L-lactide) has the highest Tg at about 65°C. 

Developers of controlled release formulations have employed polymers produced from both L-lactide and Dl -lactide. In terms of clinical studies, however, it appears that perhaps the DL-lactide formulations have been somewhat more successful. It is unclear if this is due to the DL-lactide materials being less crystalline and more permeable to most drugs or perhaps more sophisticated techniques and... 

Controlled release fiber systems based on aliphatic polyesters were investigated by Dunn and Lewis (51-54). The feasibility of hollow fibers spun from poly (L-lactide) and containing the contraceptive steroid levonorgestrel has been demonstrated (55). 

None of the early systems have enjoyed significant clinical success (67). This is most probably due to two factors. Most of the formulations were based on crystalline poly(L-lactide) rather than the... 

Several narcotic antagonists, including naloxone, naltrexone, L-methadone, and cyclazocine, have been incorporated in lactide homopolymers and lactide/glycolide copolymers. Cyclozocine was incorporated in poly(L-lactide) in the form of films (81,82). Lamination of drug-polymer films with a drug-free film created a reservoir device and eliminated the burst observed with the monolithic films originally tested. 

The use of polylactides for delivery of insect hormone analogs and other veterinary compounds (115,116) has been studied. Microspheres, pellets, and reservoir devices based on polyglycolide, poly-(DL-Iactide), poly(L-lactide), and various copolymers have been used to deliver methoprene and a number of juvenile hormone analogs. ... 

Muramyl dipeptide derivatives have also been microencapsulated in lactide/glycolide copolymers for use alone as an immuno potentiator. L-lactide/glycolide copolymers were used to deliver MDP-B30, a lipophilic compound, from very small microspheres (less than 5 pm in diameter). The amount of MDP-B30 required for tumor growth inhibitory activity of mouse peritoneal macrophages was 2000 times less for the controlled release MDP-B30 microspheres than for the unen-capsulated drug (134). 

Rudolf, R. M., Boering, G., Roseman, F., and Leenslay, J., Resorbable poly(L-lactide) plates and screws for the fixation... 

Dittrich, V. W., and Schulz, R. C., Kinetics and mechanism of the ring-opening polymerization of L-lactide, Angew. Makro-mol. Chem.. 15. 109, 1971. 

Bissery, M. C., Valeriote, F., and Thies, C., Fate and effect of CCNU-loaded microspheres made of poly(D,L) lactide (PLA) or poly B-hydroxybutyrate (PHB) in mice, Proc. Int. Symp. Control. Rel. Bioact. Mater.. 12. 181, 1985. 

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