Polymer implants

Biocompatibility. The analysis of polymer implants has been employed using FTIR spectroscopy to elucidate the long-term biocompatibility and quality control of biomedical materials. This method of surface analysis allows the determination of the specific molecular composition and structures most appropriate for long-term compatibility in humans. 

Polymer Implantation time Protein layer thickness (A) ... 

Hegyeli, A. Use of organ cultures to evaluate biodegradation of polymer implant materials. J. Biomed. Mater. Res. 7 205—214, 1973. 

Brashear, R.L. Flanagan, D. Luner, P.E. Seyer, J.J. Kemper, M.S. Diffuse reflectance near-infrared spectroscopy as a non-destructive analytical technique for polymer implants. J. Pharm. Sci. 1999, 88 (12), 1348-1353. 

These include the effect of the processing conditions on the mechanical properties of synthetic and natural polymers, the characterization of ion-implanted polymer surfaces, the study of mechanical changes in polymer implants after wear, the influence of coatings on surface properties, weatherability characterization of polymers, etc. 

I. S. Eller, T.W. Cozzens, J.W. Kenealy, J.N. Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. 

Fung LK, Ewend MG, AiUs A, Sipos EP, Thompson R, Watts M, Colvin OM, Brem H, Saltzman WM (1998) Pharmacokinetics of interstitial delivery of carmustine, 4-hydroperoxy-cyclophosphamide, and paclitaxel from a biodegradable polymer implant in the monkey brain. Cancer Res 58 672-684. 

Results. Excellent correlation between in vitro and in vivo release rates was observed (Figure 1). As in internal control, the inulln polymer squares were removed from the rats at the end of 450 hrs and rat urine analyzed 4.5 hrs later. As shown in Figure 1, the recovery rate of H-inulin dropped 300 fold. This control confirmed that H-inulin is rapidly cleared from the blood stream and excreted into the urine. Thus inulin is an excellent marker for directly assessing release rates from the polymer implant. 

In vitro and in vivo release kinetics were compared using two different approaches. In the first approach (the recovery approach) polymer implants containing a radioactively labeled substrate—,4C-labeled bovine serum albumin, /3-[14C]-lactoglobulin, or [3H]-inulin—were implanted subcutaneously into rates (in vivo) or released in phosphate-buffered saline, pH 7.4, at 37°C (in vitro). At various time points, the polymer implants were removed from the rats or the saline. They were then lyophilized to remove residual water and dissolved in xylene. When the polymer dissolved, the unreleased macromolecules precipitated to the bottom of the vial. Water was then added to dissolve the macromolecules scintillation fluid was next added, resulting in a homogeneous translucent emulsion which was counted via liquid scintillation. 

The foreign body reaction occurring around soft tissue implants and thrombosis on surfaces in contact with blood are the major reactions encountered with implants. Both reactions involve the interaction of cells with the implant, especially in the later stages, and much previous study has therefore emphasized cellular events in the biocompatibility process. However, cells encounter foreign polymer implants under conditions that ensure the prior adsorption of a layer of protein to the polymer interface. The properties of the adsorbed layer are therefore important in mediating cellular response to the material. 

Strasser, J.F., et al. Distribution of l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) and tracers in the rabbit brain following interstitial delivery by biodegradable polymer implants. Journal of Pharmacology and Experimental Therapeutics, 1995, 275(3), 1647-1655. 

Walter, K.A., et al., Interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma. Cancer Research, 1994, 54, 2207-2212. 

Assume that the drug diffuses through, and is simultaneously eliminated from, tissue in the vicinity of an implant releasing active molecules. The polymer implant is surrounded by biological tissue, composed of cells and an extracellular space (ECS) filled with extracellular fluid (ECF). Immediately... 

In many situations, drug transport due to bulk flow can be neglected. This assumption (v is zero) is common in previous studies of drug distribution in brain tissue [17]. For example, in a study of cisplatin distribution after continuous infusion into the brain, the effects of bulk flow were found to be small, except within 0.5 mm of the site of Infusion [24]. In the cases considered here, since drug molecules enter the tissue by diffusion from the polymer implant, not by pressure-driven flow of a fluid, no flow should be introduced by the presence of the polymer. With fluid convection assumed to be negligible, the general governing equation in the tissue. Equation 10-17, reduces to ... 

Controlled-release polymer implants are useful for delivering drugs directly to the brain interstitium. This approach may improve the therapy of brain tumors or other neurologieal disorders. The mathematical models described in this section—which are based on methods of analysis developed in earlier chapters—provide a useful framework for analyzing mechanisms of drug distribution after delivery. These models describe the behavior of chemotherapy compounds very well and allow prediction of the effect of changing properties of the implant or the drug. More complex models are needed to describe the behavior of macromolecules, which encounter multiple modes of elimination and metabolism and are subject to the effects of fluid flow. 

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