Polyanhydrides modeling

Modeling the behavior of bioerodible polyanhydrides is complicated by the many phenomena contributing to release profiles described in the previous section. The degradation kinetics may be coupled to other processes, such as diffusion and dissolution, and the overall erosion kinetics represent the sum of all of these multiple processes (Goepferich, 1996a). 

Many model formulations of polyanhydrides have been tested both in vitro and in vivo. The delivery schemes that polyanhydrides have been... 

Proteins may be stabilized by encapsulation in polyanhydride microspheres. Stability of proteins with respect to water-induced aggregation has been demonstrated to be a function of polymer hydrophobicity for insulin and bovine somatotropin as model proteins (Ron et al., 1993). Encapsulation and enzymatic activity of a variety of other proteins encapsulated in P(SA FAD) was studied by Tabata et al. (1993). 

The development of new polyanhydrides has sparked researchers to developed new device fabrication and characterization techniques, instrumentation, and experimental and mathematical models that can be extended to the study of other systems. The growing interest in developing new chemistries and drug release systems based on polyanhydrides promises a rich harvest of new applications and drug release technologies, as well as new characterization techniques that can be extended to other materials. Future endeavors will likely focus on multicomponent polyanhydride systems, combining new chemical functionalities to tailor polyanhydrides for specific applications. 

The release characteristics of polyanhydride systems could be used not only to develop clinical treatments, but also to induce chronic disease states as models for studying immune function. Many current models of chronic diseases are based on induction of acute effects, which do not exhibit the same long-term behavior as the disease being modeled. 

The incorporation of fatty acids into a polyanhydride chain was investigated using two fatty acids lithocholic acid and ricinoleic acid. Lithocholic acid containing polyanhydrides (Figure 2) were prepared by two step synthesis. Polyanhydrides reached molecular weights of 21000-115000 Da, depending on the polymer composition. Release of model drugs from these polymers showed sustained release of 5FU for almost 3 weeks and triamcinolone for 4 weeks (22). 

As with PLA or PLG carriers, the application of either polyanhydride or polyorthoester polymers for 5-FU sustained release in glaucoma treatment or PVR has been investigated. Using compression techniques, polyanhydride devices constructed from combinations of(p-carboxyphenoxy)alkanes with sebacic acid have been produced. Disk or T-shaped polyanhydride devices containing between 10 and 20%i 5-FU prolonged lOP reduction and bleb survival in filtration models or... 

E.-S. Park, M. Maniar, J. Shah, Effects of model compounds with varying physicochemical properties on erosion of polyanhydride devices, J. Control. Release 40 (1996) 111-121. 

Tabata, Y., Langer, R., 1993. Polyanhydride mierospheres that display near-constant release of water-soluhle model drug compounds. Pharmaceutical Research 10, 391-399. 

A biodegradable polyanhydride has been prepared by polycondensation of a lithocholic acid dimer (Scheme 11b). The homopolymer has a Tg of 85°C and a melting point of >250°C, both of which can be lowered by the incorporation of a comonomer (sebacic acid). The polymers have been subjected to degradation and release studies, using p-nitroanUine as the model drug. The degradation and release rates are found to be dependent on the copolymer composition, and no apparent toxicity is observed in vivo [110]. 

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