Polyanhydrides experiments

Pure PCPP was used for this experiment to magnify the effect. At pH 7.4, pure PCPP degrades in about 3 years, as discussed above. However, this rate increases markedly as the pH rises, and at pH 10.0, this material degrades in just over 100 days. At very acidic pH values, many of the polyanhydrides virtually do not erode at all. 

Alkaline phosphatase, an enzyme with a molecular weight of approximately 86,000, has been incorporated into a polyanhydride matrix using compression molded PCPP-SA 9 91. Five percent loaded wafers, 50 mg each, were perpared, and measured 1.4 cm in diameter, with a thickness of 0.5 mm. Release experiments were then conducted using techniques similar to those described for carmustine above. As can be seen in Pig. 13, the alkaline phosphatase was released in a well-controlled manner over a prolonged period of time, just over a month, from this polyanhydride. 

As in the alkaline phosphatase example above, p-galactosidase, an enzyme with a molecular weight of approximately 360,000, has also been incorporated into a polyanhydride and released in a well-controlled fashion. As is shown in Fig. 14, the release of 3-galactosidase was quite linear over most of the time examined, and was complete, reaching 100% release in about 800 hr. This experiment utilized 5% loaded, compression-molded wafers of PCPP-SA 9 91, 1.4 cm in diameter and 0.5 mm thick, weighing 50 mg. 

Whether in copolymers or blends, inhomogeneous erosion has a nontrivial effect on drug release kinetics as will be shown later. Leong et al. (1985) demonstrated that the pH of the degradation media also has a dramatic effect on the erosion rate, which increases with increasing pH. The acceleration of degradation of polyanhydrides with increase in pH is widely reported and has been used to speed up experiments (Shakesheff et al., 1994). 

The polyamide obtained in these experiments was identified as polynonanoamide Coffman and his coworkers had prepared this compound in 1948 via the polyanhydride of sebacic acid. The first fiber-forming polyamide was obtained by Carothers from an amino acid—viz., w-aminononanoic acid—a discovery in 1935 which led to intensified research on the polyamides and culminated in the development of Nylon 6-6. 

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. 

In the rabbit cornea bioassay, no evidence of inflammatory response was observed with any of the implants at any time. On an average, the bulk of the polymers disappeared completely between 7 and 14 days after the implantation [66]. In similar animal experiments in which polyanhydride matrices containing tumor angiogenic factor (TAF) were implanted in rabbit cornea, a significant vascularization response was observed without edema or white cells. Moreover, and most importantly from the biocompatibiUty standpoint, polymer matrices without incorporated TAF showed no adverse vascular response [67,68]. 

The physical and mechanical properties of polyanhydrides can be altered by minor modifications. Biodegradable polymer blends of polyanhydrides and polyesters have been investigated as dmg carriers (Leong et al., 1984). A polymeric blend of poly (trimethylene carbonate) (PTMC) with poly(adipic anhydride) (PAA) and the matrix of PTMC—PAA blend was found to be biocompatible in vitro and in vivo experiments as well as a promising candidate for controlled drug delivery erosion with tuneable erosion rate achieved by varying the proportion of PTMC and PAA (Edlund and... 

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