Degradation in vivo

Poly(orthoesters) represent the first class of bioerodible polymers designed specifically for dmg deUvery appHcations (52). In vivo degradation of the polyorthoester shown, known as the Al amer degradation, yields 1,4-cydohexanedimethanol and 4-hydroxybutyric acid as hydrolysis products (53). 

Like the in vitro studies, the in vivo degradation of the TMC-CL copolymers containing 89% CL showed no change in shape or size after one year. As the degradation of the TMC-CL copolymers was so slow, a mature fibrous capsule remained throughout the year. Histological results of the TMC-CL copolymers were similar to those obtained from TMC-DLLA or other commonly used biodegradable polymers. 

Wang Y, Kim YM, and Danger R. In vivo degradation characteristics of poly(glycerol sebacate). 

Many investigators have studied the in vivo degradation kinetics of lactide/glycolide materials (5,35-39). There has been some confusion in the interpretation of results primarily because of lack of consistency in nomenclature and careful attention in describing the specific stereoisomers evaluated. Nevertheless, the overall degradation kinetics are fairly well established for the entire family of homopolymers and copolymers. At the present, this common knowledge of the in vivo lifetimes of various lactide/glycolide polymers is a primary reason for their popularity. 

Brich, Z., Nimmerfall, F., Kissel, T., and Bantle, S., Branched ter-polyesters Synthesis, characterization, in vitro and in vivo degradation behaviors, Proc. Int. Symp. Control. Rel. Bioact. Mater., 15, 95, 1988. 

First, it should be stated that most of the systems to be described are erodible by nonenzymatic hydrolysis. With one exception, no evidence exists yet that an in vivo degradation is different in mechanism from an uncatalyzed chemical hydrolysis. 

Chen, P., Johnson, P., Sommer, T., Jentsch, S., and Hochstrasser, M. Multiple ubiquitin-conjugating enzymes participate in the in vivo degradation of the yeast MATa2 repressor. Cell 1993, 74, 357-69. 

In Vitro and In Vivo Degradation of Pofy(Lrlactide) Braided Multifilament Yarns... 

Hochstrasser, M., and Varshavsky, A. (1990). In vivo degradation of a transcriptional regulator the yeast o2 repressor. Cell 61,697-708. 

The in vivo degradation of PPC has been monitored for use as a surgical polymer, or as slow-release substrate. The degradability of PPC pellets in the peritoneal cavity of rats was found to be negligible after 2 months. The surface area was probably too small for substantial degradation [88]. No adverse reactions with respect to the health of the animals were reported. The interaction of PPC with various bacteria... 

Brondsted, H. and Kopecek, J. (1992). Hydrogels for site-specific drug delivery to the colon— in vitro and in vivo degradation. Pharmaceut. Res., 9, 1540-1545. 

Spenlehauer, G., Vert, M., Benoit, J.P., and Boddaert, A. (1989). In vitro and in vivo degradation of poly(DL-lactide/glycolide) type microspheres made by solvent evaporation method. Biomaterials, 10, 557-563. 

Tomihata, K. and Ikada, Y. (1997). In vitro and in vivo degradation of films of chitin and its deacetylated derivatives. Biomaterials 18, 567-575. 

We have studied the effect of irradiation on both pectin and cellulose degradation extensively, both from the standpoint of the in vivo degradation as measured by the characteristics of the extracted polysaccharides 13, 16) and in model systems utilizing in vitro techniques 10, 12, 14, 26,... 

NOE experiments confirmed the substitution pattern of chenabine, and the MS of O-acetylchenabine, which shows the same m/e 397 base peak as the alkaloid, provided further evidence for placement of the phenolic group. The CD spectrum indicates the (S ) configuration. It is not known whether 99 and 100 are in vivo degradation products of a bisbenzylisoquinoline precursor or are primary products of biosynthetic coupling (60). 

Coyhaiquine (107), C26H27N05, from Berberis empetrifolia Lam. (Ber-beridaceae), although not formally a bis alkaloid, appears to be derived by in vivo degradation of a proaporphine-benzylisoquinoline. NMR spin decoupling experiments assigned the chemical shifts of the 6a, 7a, and 7(3 hydrogens. NOE experiments then showed a 3% enhancement of the 7a-H on irradiation of the 8-H, establishing the indicated syn stereochemistry (64). 

Greenberg, B.M., V. Gaba, A. Mattoo, and M. Edelman (1987). Identification of a primary in vivo degradation product of the rapidly-tuming-over 32 kd protein of photosystem II. European Mol. Biol. Org. J., 6 2865-2869. 

Klun J. A., Schwarz M. and Uebel E. C. (1992) Biological activity and in vivo degradation of tritiated female sex pheromone in the male European corn borer. J. Chem. Ecol. 18, 283-298. 

Fig. 10. Effect of side chain length in the amino acid moiety of polydepsipeptides on the in vivo degradability...

Figure 4.12 Synthesis and in vivo degradation of PLGA polymers...

Plasmids may be incorporated into anionic or neutral liposomes (for further details on liposomes see Section 5.3.1) to ensure protection against in vivo degradation, to control disposition profiles and to enhance intracellular delivery. However, the encapsulation efficiency of plasmids is very low, because of the large dimension of plasmids compared to the internal diameter of the vesicles. 

---