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PubMed1977

Comparison of the biosynthetic and biodegradative ornithine decarboxylases of Escherichia coli.

Biosynthetic ornithine decarboxylase was purified 4300-fold from Escherichia coli to a purity of approximately 85% as judged by polyacrylamide gel electrophoresis. The enzyme showed hyperbolic kinetics with a Km of 5.6 mM for ornithine and 1.0 micronM for pyridoxal phosphate and it was competitively inhibited by putrescine and spermidine. The biosynthetic decarboxylase was compared with the biodegradative ornithine decarboxylase [Applebaum, D., et al. (1975), Biochemistry 14, 3675]. Both enzymes were dimers of 80 000-82 000 molecular weight and exhibited similar kinetic properties. However, they differed significantly in other respects. The pH optimum of the biosynthetic enzyme was 8.1, compared with 6.9 for the biodegradative. Both enzymes were activated by nucleotides, but with different specificity. Antibody to the purified biodegradative ornithine decarboxylase did not cross-react with the biosynthetic enzyme. The evolutionary relationship of these two decarboxylases to the other amino acid decarboxylases of E. coli is discussed.

Carboxy-Lyases↗

PubMed2002

Biodegradation of hydrophilic-hydrophobic hydrogels and its effect on albumin release.

The objective of this study was to examine the effects of composition ratio of a new class of bicomponent biodegradable hydrogels and the molecular weights of the constituents on the hydrolytic degradability of the hydrogels and their release of bovine serum albumin (BSA). Biodegradable hydrogels were prepared from dextran derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) over a wide range of dex-AI to PDLLAM composition ratio. The results obtained indicated that the hydrolytic degradation of these biodegradable hydrogels could be controlled by adjusting the composition ratio of dex-AI to PDLLAM or by changing their molecular weights. Along with the hydrogel degradation, water content of the hydrogels changed, and 3D porous network structure was observed. Generally, as the PDLLAM composition in the hydrogels increased, the rate of weight loss increased due to the hydrolytic degradation of the PDLLAM. The increase in molecular weights of either dex-AI or PDLLAM would decrease the degradation rate of the dex-AI/PDLLAM hydrogels. BSA release data correlated well with the hydrogel degradation profiles, suggesting that the extent and rate of BSA release would be mainly controled by hydrogel degradation. As the PDLLAM composition in the hydrogel increased, the extent and rate of BSA release also increased. An increase in the molecular weights of the hydrogel constituents, however, led to a decrease in BSA release.

Journal Article↗

PubMed1996

Development and pharmacokinetics of galactosylated poly-L-glutamic acid as a biodegradable carrier for liver-specific drug delivery.

PURPOSE: A biodegradable carrier for the liver-specific delivery of drugs was developed using poly-L-glutamic acid (PLGA) modified with galactose (galactosylated PLGA or Gal-PLGA), and its feasibility was investigated in mice. METHODS: 111In-PLGA and 111In-Gal-PLGAs were injected in mice and their distribution and biodegradation properties were studied. RESULTS: After intravenous injection. 111In-PLGA was rapidly eliminated from the plasma and recovered mainly in the kidneys and urine. Approximately 15% of the dose was recovered in the liver, predominantly in the nonparenchymal cells. 111In-Gal-PLGAs were taken up by the liver parenchymal cells. Derivatives having 16 or more galactose residues were taken up by the liver to a higher extent (> 60% of the dose). The hepatic clearance of 111In-Gal-PLGAs correlated with their number of galactose residues. 111In-Gal18-PLGA was degraded into low-molecular weight products in the liver. CONCLUSIONS: The advantageous in vivo properties of Gal-PLGA as a liver-specific biodegradable carrier of drugs were demonstrated in mice.

Animals↗

PubMed1995

Controlled release of contraceptive steroids from biodegradable and injectable gel formulations: in vivo evaluation.

PURPOSE: The purpose of this study was to investigate in vivo biocompatibility, biodegradability and biological effects of contraceptive steroids, such as levonorgestrel and ethinyl estradiol, released from gels prepared with a combination of derivatized vegetable oil (Labrafil 1944 CS) and glyceryl ester of fatty acids (Precirol ATO 5). METHODS: Biocompatibility, biodegradability, and in vivo effects of levonorgestrel and ethinyl estradiol were studied by histologic evaluation of rat tissue, visual estimate of changes in gel size, and assessment of drug effects on reproductive cyclicity of female rats, respectively, following subcutaneous injection of gel formulations. RESULTS: Histological evaluation of the tissue samples following an injection of the gel revealed an inflammatory reaction for about 7 days, after which the tissues did not show any inflammatory response. Complete degradation of the gels containing 10% wax was observed between 5 and 6 weeks. Normal rat estrous cycles were completely blocked by the contraceptive steroids released from the gels. Gel formulations containing 0.25% w/w levonorgestrel were more effective in blocking the estrous cycle of female rats compared to the oil formulations containing an identical drug loading. The duration of the biological effect induced by levonorgestrel appears to be dose-related. The gel formulation containing 2.00% ethinyl estradiol was superior to oil formulation containing an identical drug loading in terms of controlling drug release and toxicity. CONCLUSIONS: These observations suggest that Labrafil-Precirol gels are biocompatible and biodegradable. Moreover, controlled release of steroids is possible in vivo for a prolonged period of time.

Animals↗

PubMed2000

Regenerative periodontal surgery in interproximal intrabony defects with biodegradable barriers.

AIM: The comparison of the effects of guided-tissue regeneration (GTR) using 2 different biodegradable barriers (polylactide acetyltributyl citrate; polydioxanon) in 3- and 2-wall intrabony defects. METHOD: The polydioxanon barrier is an experimental membrane for GTR therapy that consists of an continuous occlusive barrier that has a layer of slings on the side that is meant to face the mucoperiosteal flap. 15 patients provided 15 pairs of similar contralateral periodontal defects: 12 predominantly 2-wall and 18 predominantly 3-wall intrabony defects. Each defect was randomly assigned to treatment with either polylactide acetyltributyl citrate (control [c]) or polydioxanon (test [t]) devices. At baseline and 6 months after surgery, clinical measurements (P1I, GI, PPD, PAL-V) were performed. RESULTS: Barrier exposure was commonly observed in both groups (control/test): 5/4 after 7 days, 9/11 after 14 days and 11/12 after 28 days postsurgically. 4 weeks after surgery, 77% of all barriers were exposed to some extent. However, both treatments revealed a significant GI reduction (p<0.05), PPD reduction [-4.63+/-1.85 mm (t), -4.17+/-1.89 mm (c); p<0.001] and PAL-V gain [3.97+/-1.17 mm (t), 3.40 mm+/-1.40 (c); p<0.001] 6 months after surgery. Regarding GI and PPD reduction as well as PAL-V gain, there were neither statistically significant nor clinically relevant differences between test and control: similar clinical results were found 6 months after surgical treatment using both biodegradable barriers. CONCLUSIONS: Based on the results of the present study, the use of both biodegradable barriers in GTR therapy may be recommended.

Absorbable Implants↗

PubMed2002

A tough biodegradable elastomer.

Biodegradable polymers have significant potential in biotechnology and bioengineering. However, for some applications, they are limited by their inferior mechanical properties and unsatisfactory compatibility with cells and tissues. A strong, biodegradable, and biocompatible elastomer could be useful for fields such as tissue engineering, drug delivery, and in vivo sensing. We designed, synthesized, and characterized a tough biodegradable elastomer from biocompatible monomers. This elastomer forms a covalently crosslinked, three-dimensional network of random coils with hydroxyl groups attached to its backbone. Both crosslinking and the hydrogen-bonding interactions between the hydroxyl groups likely contribute to the unique properties of the elastomer. In vitro and in vivo studies show that the polymer has good biocompatibility. Polymer implants under animal skin are absorbed completely within 60 days with restoration of the implantation sites to their normal architecture.

3T3 Cells↗

PubMed2002

Imaging of biodegradable osteosynthesis materials by ultrasound.

OBJECTIVE: Biodegradable osteosynthesis materials are not radio-opaque and therefore not visible on conventional X-rays. The aim of this study is to investigate the use of ultrasound for imaging biodegradable materials to detect and monitor the degradation process. METHODS: Forty-six patients had two different polylactide osteosynthesis fracture plate materials used for the fixation of midfacial fractures. A 7.5 MHz ultrasound transducer with a 4.2 x 0.9 cm footprint was used by two examiners at approximately 4-month intervals over 36 months to monitor changes of the latero-orbital and infra-orbital rims. RESULTS: Intrinsically amorphous 50 : 50 poly(D,L)lactide reached the maximum of thickness (about 300% of the initial thickness) between 14 and 18 months post-implantation and was totally resorbed in clinical and ultrasound examinations 30 months post-implantation. In 85 : 15 poly(L,D)lactide plates, the maximum of thickness (about 300% of the initial thickness) was reached between 22 and 26 months post-implantation and resorption was still in progress 36 months post-implantation. CONCLUSION: Ultrasound examinations are suitable for detecting and monitoring the degradation process of biodegradable osteosynthesis plates in the peri-orbital region.

Absorbable Implants↗

PubMed2005

Bridging small-gap peripheral nerve defects using biodegradable chitin conduits with cultured schwann and bone marrow stromal cells in rats.

Nerve regeneration requires not only an autologous, allogenous, or biodegradable scaffolding, but additional interactions with regeneration-promoting Schwann cells. Considering the pluripotency of bone marrow stromal cells into different lineages, the authors compared biodegradable conduits with the application of cultured Schwann cells and bone marrow stromal cells in a rat sciatic injury model. Simple conduit bridging served as controls. Electrophysiologic evaluation and histologic morphometrical analysis were performed after 6 weeks; both groups with cultured cells showed a statistically significantly higher number of axons, more well-shaped remyelinated axons, and an advance in clinical functional recovery (SFI) than the simple conduit-bridging group. Confocal microscopy found that bone marrow stromal cells adopted the Schwann-cell phenotype, expressing S100 protein. Considering the ease of aspiration and greater resource of bone marrow stromal cells, the implantation of a biodegradable conduit with cultured bone marrow stromal cells was capable of presenting an alternative to conduits with Schwann cells for bridging nerve defects.

Absorbable Implants↗

PubMed1998

Stimulation of fracture healing by local application of humoral factors integrated in biodegradable implants.

Growth stimulation by growth hormones or by IGF-1 is well known whereas publications about stimulation of fracture healing with these substances are rare. One of the main effects of IGF-1 is angiopoiesis which consequently may be expected to induce and accelerate the soft tissue callus formation. BMP-2 is a stimulator for osteoclasts and osteoblasts and prepares the osseous reparation. RhBMPs, mostly BMP-2, are already used in the reconstruction of the cranial vault. The main disadvantage of these proteins is the quick inactivation after about 20-30 minutes. Local stimulation without systemic effects might be avoided by releasing a low but constant dose of IGF-1 or BMP. We speculate that the combination of a reasonable implant with an integrated drug release system may enlarge the field of application of biodegradable implants in the treatment of fractures. Such an implant might remarkably reduce the time for fracture healing and also lower the costs of postoperative treatment. In this paper we report our animal models in which we have tested constructive principles of biodegradable implants, we present the first clinical experiences with polyactates (PLLA) in the osteosynthesis of children, and we describe our inventions concerning drug releasing implants. 1) PLLA-implants a) The animal models We performed on oblique osteotomy of the right metacarpal bone in 48 juvenile calves and osteoplastic reconstructions of the cranial vault in 28 juvenile Göttinger minipigs. Biodegradable osteosynthesis with PLLA implants led to results as good as with conventional materials in both animal models, so that we proceeded to clinical evaluation in children. b) The clinical application in children 35 children, aged 6 weeks to 17 years, had resorbable osteosynthesis of their cranioplasties for correction of congenital malformations and posttraumatic reconstructions. The follow-up ranged from 5-15 years. 2) Invention of a drug-releasing system IGF-1 or BMP-2 is planned to be incapsulated by evaporation technique into nanospheres of low PDLLA (Poly-DL-Lactite) with a molecular weight of about 20,000 and an expected resorption time of 2-3 weeks (patent pending). 3) Concept of our drug-releasing resorbable implants Plates could be built up in multilayers of PDLLA sheets, separated by a spongiform matrix containing the IGF-1- or BMP-2-loaded nanospheres. The screws are hollow due to an internal driving system. The specially designed thread could also contain nanospheres, which would be brought into the cortical bone and the medullary space. The cavity of the screw is filled up with nanospheres after tightening.

Absorbable Implants↗

PubMed2005

Biodegradable X-ray markers of controlled radio-opacity. Temporary position measurements in bone.

In order to analyze X-ray markers for potential use in biodegradable implants or radiostereogrammatic analysis (RSA), we combined iopromide contrast fluid with biodegradable calcium phosphate cement. The radio-opacity of 10 x 10 mm markers containing different iodine concentrations (0, 120, 240, 360 and 720 mg per gram cement) was compared to an aluminium wedge of increasing (1-10 mm) thickness. The addition of iopromide increased the radio-opacity in a dose-dependent manner, which was comparable to 9-mm aluminium at concentrations of 240-720 mg/g. Radiographs of markers placed in explanted rabbit and in human femora were made to investigate the clinical accuracy for position determination. Markers of 1 x 1 mm (120 mg/g) were clearly discernable in all femora, and could be used to adequately measure distances of 5-45 mm (accuracy 0.10-2.19 mm). These markers might be embedded in biodegradable implants or used as temporary markers in the bone to analyze postoperative position on radiographs.

Absorbable Implants↗

PubMed2005

FK506 in a biodegradable glycolide-co-clatide-co-caprolactone polymer for prolongation of corneal allograft survival.

PURPOSE: FK506 has been extensively used in preventing immune rejection for human organ transplantation. This study aimed to evaluate the effects of a biodegradable FK506 drug delivery system (DDS) implanted into anterior chamber for the prolongation of corneal allograft survival in high-risk keratoplasty. METHODS: Biodegradable glycolide-co-clatide-co-caprolactone polymer (PGLC) was used as drug carrier to be incorporated with 0.5 mg of FK506 powder. The drug release from the FK506-PGLC DDS was evaluated in vitro and in vivo. The FK506-PGLC DDS was implanted into the anterior chamber of 12 high-risk keratoplasty rabbits. The graft survival time and clinical features of the FK506-PGLC DDS group were compared with the untreated, PGLC DDS, cyclosporin A-PGLC DDS, and 0.5% FK506 drops groups. The histopathological examination was performed to evaluate the safety of the FK506-PGLC DDS. RESULTS: The mean graft survival time was longest (> 180 days) in the FK506-PGLC DDS group. In vivo, the FK506 concentration in aqueous humor peaked on day 28 (17.9 +/- 2.3 ng/ml) and kept a sustained release for at least 168 days. No adverse reactions were observed in the FK506-PGLC DDS group. CONCLUSIONS: Biodegradable FK506-PGLC DDS implanted into anterior chamber can effectively prevent immune rejection in high-risk keratoplasty model, presenting a promising approach for the prolongation of corneal allograft survival.

Absorbable Implants↗

PubMed2003

Biodegradation-based polymer surface erosion and surface renewal for foul-release at low ship speeds.

Non-toxic foul-release provides an environmentally friendly and sustainable technical solution to control micro- and/or macrofouling on ships' hulls. Silicone-based coatings have been used for foul-release at high or moderate ship speeds (> 15 knots). To remove the fouling from slower ships (< 15 knots), the macrofoulers in particular, biodegradable polymers may be used to make the coating surface self-renewable. Synthesized by micro-organisms for carbon and energy storage under controlled conditions, polyhydroxyalkanoates (PHAs) are hydrophobic bipolymers that are gradually decomposed into CO2 and water in the environment. Because of their hydrophobic property and lack of hydrolysis in sterile aqueous solution, PHAs do not dissolve in water, but erode at the polymer surface (2-5 microns in depth) catalyzed exclusively by microbial enzymes (depolymerases) that are attached on the solid surface. The thin-layer surface erosion behaves like a self-renewable surface coating, which approaches a constant renewal rate at a relative hydraulic speed as low as 3 knots. A turbulence eddy model is used to describe the effect of energy consumption per mass of liquid on the turbulent shear stress and the surface renewal rate. Furthermore, the polymer biodegradation or surface renewal rate can be controlled within a broad range by blending the material with polymers such as poly (epsilon-caprolactone) (PCL). The biodegradation of binary blends of PHA/PCL of different compositions was quantitatively monitored by means of weight loss and Raman spectroscopy.

Biofilms↗

PubMed2002

Radioprotection, pharmacokinetic and behavioural studies in mouse implanted with biodegradable drug (amifostine) pellets.

PURPOSE: We evaluated the use of a subcutaneously (s.c.) implantable, biodegradable pellet as a drug delivery system for the radioprotector amifostine. MATERIALS AND METHODS: Mice were implanted s.c. with either the custom-made biodegradable amifostine drug pellet or the placebo pellet without amifostine, exposed to cobalt-60 gamma-radiation (bilateral, 1 Gy min(-1), 7-16 Gy), and the 30-day survival rate was monitored. The non-irradiated mouse was used for pharmacokinetic and behavioural tests. RESULTS: Significant radioprotection (85-95% survival) at 10 Gy was observed in the three-amifostine pellet implanted group 3-5 h after implantation. LD50/30 was 7.97, 8.74 and 16.64 Gy for the control, three-placebo pellet (dose reduction factor, DRF=1.10, p<0.01), and three-amifostine pellet (DRF=1.79, p<0.01) groups respectively in mouse exposed to radiation 2h after implantation. Radioprotection at 12 Gy was observed up to 4h after s.c. amifostine administration and up to 3h after implantation. Pharmacokinetic data revealed that the three-amifostine pellet group had sustained blood WR-1065 levels at 2 h after implantation, in contrast to the reported sharp peak at 30 min for s.c. administration. Although locomotor activity was significantly reduced (p<0.01) in the amifostine pellet group, the onset of the locomotor decrement was delayed as compared with groups that received 400 and 750 mg kg(-1) s.c. amifostine. CONCLUSIONS: Amifostine in biodegradable implant was effective. The radioprotection observed was comparable between conventional s.c. administration of the drug and implantation. Pharmacokinetic data and locomotor activity suggest that the implantation was beneficial though radioprotection data warrants formulation improvements in implants.

Amifostine↗

PubMedDate not supplied

Microencapsulation of superoxide dismutase into biodegradable microparticles by spray-drying.

The aim of this work was to encapsulate superoxide dismutase (SOD) into biodegradable microparticles by spray-drying technique. The nature of the organic solvent to dissolve the polymer, the method of incorporation of the drug in the organic phase (with or without a surfactant, namely sucrose ester of HLB = 6), the surfactant/polymer ratio, and the nature of the biodegradable polyesters were investigated as formulation variables. The polyesters investigated as matrix were poly(epsilon-caprolactone) (PCL), poly(d, l, lactide-co-glycolide) (PLG-RG756), and poly(d, l-lactide) (PLA-R207) of respective molecular weight 78.2 kDa, 84.8 kDa, and 199.8 kDa. At surfactant/polymer ratio of 1/10, the SOD-retained enzymatic activities were higher (> 95%) for PLG-RG756 and PLA-R207 but relatively lower for the PCL (approximately 85%) probably due to the PCL relatively higher hydrophobicity. The obtained microparticles exhibited average volume mean diameter of 4-10 microm, the smaller for PCL and the larger for PLG-RG756 polymeric matrix. The in vitro release profile showed that SOD was completely (100%) released from PLA-R207 in 48 hr and from PLG-RG756 and PCL within 72 hr. These results showed that spray-drying with incorporation of surfactant such as sucrose ester may efficiently encapsulate SOD into biodegradable microparticles. Such formulations may improve the bioavailability of SOD and similar biopharmaceuticals.

Algorithms↗

PubMed2004

Synergistic effects of micropatterned biodegradable conduits and Schwann cells on sciatic nerve regeneration.

This paper describes a novel biodegradable conduit that provides a combination of physical, chemical and biological cues at the cellular level to facilitate peripheral nerve regeneration. The conduit consists of a porous poly(D,L-lactic acid) (PDLLA) tubular support structure with a micropatterned inner lumen. Schwann cells were pre-seeded into the lumen to provide additional trophic support. Conduits with micropatterned inner lumens pre-seeded with Schwann cells (MS) were fabricated and compared with three types of conduits used as controls: M (conduits with micropatterned inner lumens without pre-seeded Schwann cells), NS (conduits without micropatterned inner lumens pre-seeded with Schwann cells) and N (conduits without micropatterned inner lumens, without pre-seeded Schwann cells). The conduits were implanted in rats with 1 cm sciatic nerve transections and the regeneration and functional recovery were compared in the four different cases. The number or size of regenerated axons did not vary significantly among the different conduits. The time of recovery, and the sciatic function index, however, were significantly enhanced using the MS conduits, based on qualitative observations as well as quantitative measurements using walking track analysis. This demonstrates that biodegradable micropatterned conduits pre-seeded with Schwann cells that provide a combination of physical, chemical and biological guidance cues for regenerating axons at the cellular level offer a better alternative for repairing sciatic nerve transactions than conventional biodegradable conduits.

Absorbable Implants↗

PubMed2001

Enhancement of chondrogenic differentiation of human articular chondrocytes by biodegradable polymers.

Biodegradable polymers are attractive candidates for chondrocyte embedding and transplantation in cartilage tissue engineering. In an attempt to determine the effects of a variety of biodegradable materials on cartilage proliferation and extracellular matrix production, poly-L-lactic acid (PLLA) with a molecular weight of 5,000, polyglycolic acid (PGA) with a molecular weight of 3,000, and copolymer of poly(L-lactic acid-glycolic acid) 50:50 (PLGA) with a molecular weight of 5,000, were dissolved in DMSO and added into the medium for 4 weeks in in vitro high-density micromass culture of multiplied human articular chondrocytes (HAC). PLLA with a molecular weight of 270,000 (PLAO3) was used as thin film. Cell proliferation and differentiation in these biomaterials were compared with tissue culture polystyrene (TCPS) as a control. Alamar blue and alcian blue staining were carried out to determine the chondrocyte proliferation and differentiation, respectively. Samples exposed to these biomaterials promoted cell proliferation in the range of 86-105% of the control proliferation, and a slight but significant increase in cell proliferation was noted only in the culture exposed to PLGA. The sample exposed to PGA elicited a significant 3.7-fold higher (p < 0.01) cell differentiation than controls and was significantly higher than that of the samples exposed to PLLA, PLAO3, and PLGA. After 4 weeks of culture, the cell differentiation from most to least was in the following order PGA > PLAO3 > PLGA = PLLA > Cont. = DMSO. Chondrocyte differentiation of the samples exposed to various biomaterials were significantly higher compared with controls. Thus, serially passage chondrocytes are competent for cell growth and quantifiable matrix production, and biodegradable polymers, especially PGA, hold promise as suitable substrates for scaffolding materials for human cartilage tissue engineering.

Biocompatible Materials↗

PubMed2002

Synthesis, biodegradability, and biocompatibility of lysine diisocyanate-glucose polymers.

The success of a tissue-engineering application depends on the use of suitable biomaterials that degrade in a timely manner and induce the least immunogenicity in the host. With this purpose in mind, we have attempted to synthesize a novel nontoxic biodegradable lysine diisocyanate (LDI)- and glucose-based polymer via polymerization of highly purified LDI with glucose and its subsequent hydration to form a spongy matrix. The LDI-glucose polymer was degradable in aqueous solutions at 37, 22, and 4 degrees C, and yielded lysine and glucose as breakdown products. The degradation products of the LDI-glucose polymer did not significantly affect the pH of the solution. The physical properties of the polymer were found to be adequate for supporting cell growth in vitro, as evidenced by the fact that rabbit bone marrow stromal cells (BMSCs) attached to the polymer matrix, remained viable on its surface, and formed multilayered confluent cultures with retention of their phenotype over a period of 2 to 4 weeks. These observations suggest that the LDI-glucose polymer and its degradation products were nontoxic in vitro. Further examination in vivo over 8 weeks revealed that subcutaneous implantation of hydrated matrix degraded in vivo three times faster than in vitro. The implanted polymer was not immunogenic and did not induce antibody responses in the host. Histological analysis of the implanted polymer showed that LDI-glucose polymer induced a minimal foreign body reaction, with formation of a capsule around the degrading polymer. The results suggest that biodegradable peptide-based polymers can be synthesized, and may potentially find their way into biomedical applications because of their biodegradability and biocompatibility.

Biocompatible Materials↗

PubMed1989

Biocompatibility of a biodegradable, controlled-release polymer in the rabbit brain.

The biodegradable polyanhydrides are a new class of controlled release polymers developed for the interstitial delivery of drugs to their target site in the brain or other organs over periods ranging from days to years. These polymers can release molecules of any size in a predictable fashion. Their degradation products are non-cytotoxic and biocompatible. The biocompatibility of a biodegradable polyanhydride, the copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP-SA) in a 50:50 formulation, was studied in the rabbit brain. Twenty adult New Zealand White male rabbits underwent implantation of PCPP-SA in a frontal lobe and absorbable gelatin sponge (Gelfoam) in the other frontal lobe. The animals were evaluated daily until the time of sacrifice. Groups of four animals were sacrificed sequentially on post-operative days 1, 3, 7, 21, and 60, and the brains processed for histological evaluation. None of the animals showed behavioral changes or neurological deficits suggestive of toxicity and all that received implants survived to their date of sacrifice. The histological examination showed no significant differences between the tissue reaction from PCPP-SA compared to Gelfoam. The polymers were also tested in the rabbit cornea bioassay and did not induce an inflammatory response. We conclude that PCPP-SA (50:50), a new biodegradable polymeric matrix that can be surgically implanted for the interstitial delivery of drugs in the brain, is biocompatible in the rabbit brain.

Animals↗