Poly subcutaneous implantation

The development of a bioerodible implant capable of releasing controlled amounts of a contraceptive steriod from a subcutaneous implant for periods of time ranging from three months to about a year has been in progress for many years. The three principal bioerodible polymers currently in use are copolymers of lactic and glycolic acid (25), poly(e-caprolactone) (26), and poly (ortho esters) (14). The desire to develop such a contraceptive system was the principal motivation for the initial development of the poly(ortho ester) polymer system. 

Next, a 1 year subcutaneous implantation study in mice was performed (22). Small pieces of poly(N-palmitoylhydroxyproline ester) (approximately 10 mg per implant) were implanted subcutaneously in the dorsal area of the animals. The implants were placed between the dermis and the adipose tissue layer. Groups of mice were sacrificed 4, 7, 14, 16, and 56 weeks postimplantation. 

Although the initially reported tissue compatibility tests for subcutaneous implants of poly(BPA-iminocarbonate) were encouraging (41,42), it is doubtful whether this polymer will pass more stringent biocompatibility tests. In correspondence with the properties of most synthetic phenols, BPA is a known irritant and most recent results indicate that BPA is cytotoxic toward chick embryo fibroblasts in vitro (43). Thus, initial results indicate that poly(BPA-iminocarbonate) is a polymer with highly promising material properties, whose ultimate applicability as a biomaterial is questionable due to the possible toxicity of its monomeric building blocks. 

In order to test the tissue compatibility of tyrosine-derived poly-(iminocarbonates), solvent cast films of poIy(CTTH) were subcutaneously implanted into the back of outbread mice. In this study, conventional poly(L-tyrosine) served as a control (42). With only small variations, the experimental protocol described for the biocompatibility testing of poly(N-palmitoylhydroxyproline ester) (Sec. III. 

The present study investigates a biodegradable polymer, poly(DL-lactic acid) (DL-PLA), as the microcapsule wall. Tablets of microcapsules prepared with this method should be capable of use as subcutaneous implants. Three different compression forces, 2, 5 and 10 kN, were used, with core wall ratios of 1 1 and 2 1. For comparison, the same proportions of drug and coating polymer were compressed without prior microencapsulation. 

Figure 3.1 H E section showing foreign body giant cells obtained 28 days after subcutaneous implantation of aporous poly vinyl alcohol implant in arat. Reprinted with permission from Ref. 10. Copyright 2004 John Wiley Sons. 

Block terpolymers prepared by Cheng [5] consisting of poly(A-isopropyl acrylamide-b-polyethyleneoxide-b-A-isopropyl acrylamide), (II), were effective as thermally reversible gels and used as subcutaneous implants, joint or tissue spacers, and biological filler for wrinkles or cosmetic implants. Methacrylamide analogues were prepared by Gutowska [6]. 

Kosdiwanez, H.E., Yap, F.Y., Klitzman, B., and Reichert, W.M. (2008) In vitro and in vivo characterization of porous poly-L-lactic add coatings for subcutaneously implanted glucose sensors. Journal of Biomedical Materials ResearchPart A, 87A (3), 792-807. 

The in vivo tissue reactions and biodegradations of poly(3-hy-droxybutyrate-co-3-hydroxyhexanoate), and other polymers have been evaluated by subcutaneous implantation in rabbits. The results revealed that the degradation rate increased in the order of poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxy-hexanoate), poly(lactic acid) (PLA). During the implantation period, the crystallinity of p oly(3-hydroxybutyrate-co-3-hydroxyhexanoate) increased from 19% to 22% and then dropped to 14%. The results suggest that a rapid degradation occurs in the amorphous region rather than in crystalline region (21). 

Poly[trimellitylimidoglycine-co-1,6-bis(p-carboxyphenoxy)hexane] developed for subcutaneous implantation. ... 

The same result has been found by Lagone et al, (1995) who used poly[(ethyl-alanate)-co-(imidazole)phosphazene] derivatives for in umo evaluation. Films of this polymer type were subcutaneously implanted in rats. The animals were killed after 30 days, or 60 days. Biopsy samples of the implant zone were histologically examined. In both cases the animals were healthy. The biological material surrounding the polymer was found to correspond to fibroblast collagen with only a few monocytes in the internal site. 

Implantation is done subcutaneously, in the bone, or in the brain. For subcutaneous implantation, a silicone membrane is used. However, this must be taken out after completion of drug delivery. Currently, development is underway for a biodegradable DDS using poly(lactic acid-co-glycol). For implantation in the brain, a few methods have been tried. For... 

Rentsch, C., Rentsch, B., Breier, A. et al. 2010. Evaluation of the osteogenic potential and vascularization of 3d poly(3)hydroxybutyrate scaffolds subcutaneously implanted in nude rats. / Biomed Mater Res A 92A 185-95. 

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