GLYCOLIDE COPOLYMER

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). 

T Niwa, H Takeuchi, T Hino, N Kunou, Y Kawa-shima. Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with d,l-lacti-de/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior. J Control Rel 25 89-98, 1993. 

In-Vivo Absorption and breaking strength retention studies. For comparing PDS monofilament in-vivo properties with copolymeric fibers, a second 90/10 PDO/glycolide copolymer (II-A) was prepared and processed following similar schemes to those used for copolymer II. 

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. 

Poly(lactide-co-glycolide) copolymers have been developed for both device and drug delivery applications. 

TABLE 1. Scoping reactions for preparing random poly(lactide-co-glycolide) copolymers using the experimental catalyst di-[di-(trimethylsilyl)amine]stannate. 

Kawashima, Y. (1995). Aerosolization oflactide/glycolide copolymer (PLGA) nanospheres for pulmonary delivery of peptide-drugs. Yakugaku Zasshi 115, 732-741. 

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... 

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