Lactide—glycolide copolymers

The features of the copolymers depend on the type, number, length and sequence of the monomer combinations. The most common monomer used in the ring-opening copolymerization process of lactide is glycolide and it can be randomly distributed in 

Encapsulation and delivery of anticancer, diabetes, psychotic, restenosis, tetanus, pulmonary, immunomodulatory agents [374], growth factors and hormones in PLGA nanoparticles has been reported [360,375]. They keep the ability to release the bioactive agent in a number of administration sites. PLGA microspheres have successfully incorporated nonsteroidal anti-inflammatory drugs for the treatment of arthritis and related diseases [376]. 

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Several investigators have utilized the 85 15 DL-lactide/glycolide copolymer for 90-day delivery of bioactive agents. This polymer is essentially bioeroded by about 150 days, thus making the 85 15 a useful matrix for 90-day systems. 

Experiments in rats (38) have shown that y irradiation decreases the inherent viscosity of lactide/glycolide copolymers and increases the biodegradation rate. The in vivo lifetime of a 92 8 DL-lactide/ glycolide copolymer was decreased from about 40 weeks to about 30 weeks after treatment with 2 Mrad of y irradiation. 

Recent studies on 85 15 and 50 50 copolymers show decreases of about 15—20% in inherent viscosity after treatment with 2.0-2.5 Mrad of y rays. For example, an 85 15 DL-lactide/glycolide copolymer showed a drop in inherent viscosity from 0.71 to 0.56 dl/g (30°C in chloroform) upon treatment with 2.41 Mrad of y radiation. In most... 

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. 

Naltrexone in combination with lactide/glycolide copolymer has been investigated (83-87). Chiang (85) reported the clinical evaluations of a bead preparation containing 70% naltrexone and 30% of a 90 10 lactide/glycolide copolymer. Each subject received a 10-mg i.v. dose of naltrexone and a 63-mg dose by subcutaneous implantation of the beads. Average plasma naltrexone levels were maintained at 0.3-0.4 ng/ml for approximately 1 month. Two out of three subjects experienced a local inflammatory reaction at the site of implantation. This unexplained problem prevented further clinical testing of... 

FIGURE 6 Scanning electron micrograph of 90-day testosterone microspheres based on 85 15 lactide/glycolide copolymer. 

Various antimalarial drugs have been studied in biodegradable delivery systems. Wise (89) reported the use of a lactide/glycolide copolymer and also poly(L-lactic acid) for release of drugs such as quinazoline and sulfadiazine. Although in vitro data and experiments in mice were somewhat encouraging, these early formulations failed to reach significant clinical status. 

Several antiinflammatory compounds have been formulated in lactide/ glycolide polymers (107-111). Methylprednisolone microspheres based on an 85 15 DL-lactide/glycolide copolymer were developed for intra-articulate administration (111). The microspheres, prepared by a solvent evaporation procedure, are 5—20 jam in diameter and are designed to release low levels of the steroid over a extended period in the joint. Controlled experiments in rabbits with induced arthritis showed that the microspheres afforded an antiinflammatory response for up to 5 months following a single injection. 

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). 

Calcitonin, LHRH, lypressin, and somatostatin have been formulated in lactide/glycolide copolymers as injectable, controlled release formulations (117). Various agonistic and antagonistic analogs have been studied. Generally these compounds are hydrophilic polypeptides,... 

Kent et al. first reported on the feasibility of controlled release LHRH analogs from a 50 50 lactide/glycolide copolymer (118,119)... 

Fig. 10). A phase separation microencapsulation technique was used to formulate nafarelin acetate in 50 50, 69 31, and 45 55 DL-lactide/glycolide copolymers (120). 

A series of DL-lactide/glycolide copolymers and the lactide honiopoly-mer were screened in vitro and in vivo with nafarelin. More than 8 months release was achieved with certain implants. 

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). 

Kawashima, Y., Yamamoto, H., Takeuchi, H., Fujioka, S., and Hino, T. (1999). Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hypoglycemic effect. J. Controlled Release, 62, 279-287. 

Kawashima, Y., et al. 2000. Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm Dev Technol 5 77. 

The more recent development of a slow-release (depot) formulation of goserelin [81 ] has allowed the administration of the agonist as a single monthly injection. Such a depot preparation has obvious clinical advantages. The peptide was incorporated in a 50 50 lactide-glycolide copolymer in the form of a small cylindrical rod, which can be injected, under local anaesthesia, through a 16-gauge needle, into the subcutaneous tissue of the anterior abdominal wall. 

Katti, K. S., Sikdar, D., Katti, D. R., Ghosh, P. Verma. D. (2006). Molecular interactions in intercalated organically modified clay andclay-polycaprolactam nanocomposites Experiments and modeling. Polymer, Vol. 47, No. 1, pp. 403-414 Kister, G., Cassanas, G. Vert, M. (1998). Structure and morphology of solid lactide-glycolide copolymers from n.m.r., infra-red and Raman spectroscopy. Polymer, Vol. 39, No. 15, pp. 3335-3340... 

Thermoplastic materials based on lactide/glycolide copolymers have been used to produce absorbable staples for skin and internal wound closures. These staples consist primarily of two interlocking components, a fastener and receiver. They are advantageous in that they provide a quick means of closure with comparable infection resistance. They are limited to locations which do not have large tensile loads and/or thicker or more sensitive tissue. 

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