The biodegradation of the copolymer 50:50 poly(DL-lactide-co-glycolide)-lypressin microcapsules was studied by light and electron microscopic methods and 14C release. Intramuscular injection sites of microcapsules in rats were studied by dissecting and conventional light microscopy as well as scanning (SEM) and transmission electron microscopy. A minimal localized acute myositis was seen initially at the injection sites. By Day 4, a few small foreign body giant cells were present participating in the minimal foreign body response. Later the inflammatory cells decreased and the individual microcapsules were walled off by immature fibrous connective tissue and large syncytial foreign body giant cells. By Day 35, definitive changes in some microcapsules, consisting of a granular and slightly eroded appearance of the internal matrix, were seen by SEM. By Day 42, the outer rims of the microcapsules were extensively eroded. At Day 56, the inflammatory and connective tissue reactions were almost completely resolved and biodegradation continued so that only remnant pieces of the microcapsules were present at Day 63. The morphologic picture correlated well with loss of 14C radioactivity, which could no longer be detected at the injection sites on Day 56. Phagocytosis did not seem to be an important factor in the biodegradation.
Exploration of the effects of "minor" structural differences on the antitumor activity and toxicity of dimeric Catharanthus alkaloids resulted in the preparation of deacetylvinblastine amide (vindesine, VDS) from either vinblastine (VLB) or deacetylvinblastine. Adequate amounts of vindesine for biological testing were prepared by preferential hydrazinolysis of the C23-ester in the vindoline moiety of VLB, followed by hydrogenolysis of the resulting deacetylvinblastine hydrazide. Vindesine in its activity spectrum against rodent tumor systems resembles vincristine (VCR) rather than its parent VLB, while its neurotoxic potential appears to be less than that of VCR. The experimental models developed to estimate this potential include in vitro measurements of axoplasmic transport effects in the cat sciatic nerve and the estimation of neuromuscular disturbances in chickens and monkeys by vindesine in comparison with VCR. A radioimmunoassay for VLB, VCR, and VDS, developed by means of deacetylvinblastine acid azide, has been used to study the pharmacokinetics of vindesine in man. The clinical investigation of vindesine is in progress. Deacetylvinblastine, in contrast to earlier reports, showed activity against several murine tumor systems.
Three different sieve size fractions of ergot-containing biodegradable microcapsules were examined both in vitro and in vivo. The sieve sizes and average particle diameter, (micron), were: less than 45-75 (mean = 30); 75-106 (mean = 79); 106-177 (mean = 130). These microcapsules contained ca. 9% drug and were produced from 50:50 poly(DL-lactide-co-glycolide). The objective was to determine the effect of particle size on in vivo and in vitro degradation rates. The microcapsules were injected into rat gastrocnemius muscle and excised and examined at various time points up to 70 days. Initially a minimal tissue response was noted which was characterized by a sharply localized acute inflammatory reaction. Following this, connective tissue and foreign body giant cells engulfed the microcapsules at 20-30 days. Only vestiges of the microcapsules were found surrounded by minimal connective tissue and foreign body giant cells after 60-70 days. The tissue reaction was a minimal, sharply localized foreign body giant cell and connective tissue process for all three size groups of microcapsules. The largest microcapsules (mean = 130 microns) exhibited a slightly greater tendency to undergo in vivo and in vitro degradation relative to the other groups. However, it can be concluded that over the microcapsule size ranges examined minimal differences in the degradation properties of the polymeric matrices and consequently those of the microcapsules were noted.
Biodegradable microcapsules have been shown to be capable of delivering a sustained release of various medicinal agents. We have observed an initial minimal, sharply localized, acute inflammatory response to intramuscularly injected microcapsules produced from various polymers. Evaluation of later time points has shown a diminishing macrophage, foreign body giant cell, and connective tissue response along with actual microcapsule degradation. No fibrous capsule formation was seen. Complete resolution of the tissue reaction can be expected, with the time frame depending upon the polymer utilized. Published experimental results report similar minor tissue responses to a variety of injected biodegradable microcapsules.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.