Biocompatibility polyanhydrides

Implants in the rabbit corneas exhibited no observable inflammatory characteristics over a period of 6 weeks. Compared to other previously tested polymers, the inertness of these polyanhydrides rivals that of the biocompatible poly(hydroxyethyl methacrylate) and ethylene-vinyl acetate copolymer. Histological examination of the removed corneas also revealed the absence of inflammatory cells (21)... 

The synthesis of poly(anhydride-co-amide)s (Table VII) of various chemistries was pursued by Hartmann and Schulz (1989) as a means of improving biocompatibility and extending the degradation times of polyanhydrides. This work also contains calorimetry data on the thermal transitions and spectroscopic characterization. 

Biocompatibility is an essential property of new biomaterials for drug delivery. Biocompatibility is always assessed with respect to specific applications and may be assessed with respect to cytotoxicity, allergic responses, irritation, inflammation, mutagenicity, teratogenicity, and carcinogenicity (Katti el al., 2002). The reviews by Katti et al. (2002) and Domb et al. (1997) provide good discussions on the biocompatibility studies that have been conducted with polyanhydrides over the past two decades. 

Biodegradable polymers, both synthetic and natural, have gained more attention as carriers because of their biocompatibility and biodegradability and therewith the low impact on the environment. Examples of biodegradable polymers are synthetic polymers, such as polyesters, poly(orfho-esters), polyanhydrides and polyphosphazenes, and natural polymers, like polysaccharides such as chitosan, hyaluronic acid and alginates. 

Biocompatible ortho aromatic polyanhydrides, (IV), prepared by Uhrich [5] were used in drug delivery systems and as scaffolding implants for tissue reconstruction. 

Fatty acids have been used previously in the development of polymers for biomedical applications as they are considered to be inert, inexpensive and biocompatible. The main fatty acids which are used as a base for synthesis of biomedical polymers (polyanhydrides) are stearic acid (/), erucic acid (C22 unsaturated fatty acid) dimer (2), bile acid dimer (i), ricinoleic acid 4) and other fatty acids (5), middle long carbon chain (C12 - 15) dibasic acids, such as dodecanedioic, brassylic acid, tetradecandioic acid and pentadecandioic acid (/). 

The release of a number of drugs from polyanhydride matrices has been studied including ciprofloxacin, p-nitroaniline, cortisone acetate, insulin, and a variety of proteins. ° In many instances, drug release was reported to coincide with polymer degradation. The biocompatibility of polyanhydrides has... 

Leong, K.W. D Amore, P. Marietta, M. Danger, R. Bioerodible polyanhydrides as drug-carrier matrices. II biocompatibility and chemical reactivity. J. Biomed. Mat. Res. 1986, 20, 51-64. 

Several other biodegradable, biocompatible, injectable polymers are being investigated for drug delivery systems. They include polyvinyl alcohol, block copolymer of PLA-PEG, polycyanoacrylate, polyanhydrides, cellulose, alginate, collagen, gelatin, albumin, starches, dextrans, hyaluronic acid and its derivatives, and hydroxyapatite. ... 

The biocompatibility of implantable polyanhydride disks was studied in the brain of rats, rabbits, monkeys, and eventually in human clinical trials. Wafers of poly(CPP SA) and poly (FAD SA) were implanted in the frontal lobes of rats, rabbits, and monkeys. In all these studies, the animals receiving the implants showed no behavioral changes or neurological deficits, indicating that the polymers were not invoking a systemic or local toxicity. To determine how the body metabolized the poly(CPP SA), radio-labeled copolymers were implanted in the brains of rats. Seven days after the implantation, 40% of the " C SA-labeled polymer had been excreted as CO2, 10% was excreted along with the urine, 2% with the feces, and 10% still in the implanted device. In the same period only 4% of the " C CPP-labeled polymer was excreted along with the urine and feces. 

With these preclinical toxicology and biocompatibility studies carried out in animals having demonstrated both the efficacy and safety of the polyanhydrides, studies involving these materials moved toward human clinical use. In 1987, the Food and Drug Administration approved experimental use of these polyanhydrides in humans, under an Investigational New Drug clinical trial application. A Phase I/II clinical trial of 21 patients in five U.S. hospitals was carried out... 

Initial biocompatibility studies were conducted on polyanhydrides. As evaluated by mutation assays (29), the degradation products of the polymer were non-mutagenic and non-cytotoxic. Teratogenicity tests were also negative. Growth of mammalian cells in tissue culture was also not affected by these polymers (29). 

This chapter explores the development of biodegradable polyanhydride polymers as a local chemotherapeutic delivery system in brain tumor patients. In so doing, the authors detail the unique pharmacokinetic considerations inherent in CNS drug delivery, and the resultant advantages of local administration. Subsequent sections chronicle the development of biocompatible technologies, preclinical and clinical experience with polymer-based tumor treatments, and potential future advancements in local antineoplastic drug delivery. 

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