Polymer degradation and drug release

Septicin antibacterial implant for the treatment of chronic bone infections have been developed [21-24]. The multidisciplinary concept of polymeric implants has expanded to include research on the chemistry and characterization of polymers, experimental and theoretical polymer degradation and drug release, toxicology and metabolism, and research in specific fields of applications such as cancer, proteins and hormones delivery, infectious diseases, and brain disorders. This chapter concentrates on the chemistry and characterization of polyanhydrides with a brief description on recent applications of polyanhydrides. 

The morphology of polyanhydride was studied by Scanning Electron Microscope (SEM) to elucidate the mechanism of polymer degradation and drug release from polyanhydrides [67]. Microspheres prepared by three different... 

Experiments were also performed to evaluate whether the extent of enhancement could be regulated externally. By varying the ultrasound intensity, the degree of enhancement for both polymer degradation and drug release for the bioerodible and non-erodible systems could be altered 10-fold (42). 

Degradation and disappearance of a biodegradable polymer matrix occurs in a sequence of steps. Some of these steps are understood reasonably well as a consequence mathematical expressions can be used to describe some aspects of polymer degradation and drug release. These mechanisms will be illustrated using the pLGA system. 

Typically, the processed polymeric nanoparticles are stable in the blood stream and elsewhere in the body [20]. Their degradation and drug release are determined by the chemical degradation rate of the polymer such as poly(lactide) and poly(glycolide). Such nanopartides can be used for site-spedfic intracellular drug delivery if they have targeting moieties on the surface. 

Figure 7 Principle of a Monte Carlo-based approach to mathematically model polymer degradation and drug diffusion in PLGA-based microparticles. Scheme of the iimer structure of the system (one-quarter of a spherical cross section) (A) at time t = 0 (before exposure to the release medium) and (B) during dmg release. Gray, dotted, and white pixels represent nondegraded polymer, drag and pores, respectively. Source From Ref. 48.

Arosio, P., Busini, V., Perale, G., Moscatelli, D. Masi, M. 2008. A new model of resorbable device degradation and drug release - Part I zero order model. Polymer International, 57, 912. 

Hurrell, S. and Cameron, R. E., The effect of buffer concentration, pH and buffer ions on the degradation and drug release from polyglycolide. Polymers International 52, 358-366 (2003). 

Noorsal, K., Mantle, M.D., Gladden, L.F., Cameron, R.E., 2005. Degradation and drug-release studies of a poly(glycohde-co-trimethylene carbonate) copolymer (Maxon). Journal of Applied Polymer Science 95, 475—486. 

Alexis, F., 2005. Factors affecting the degradation and drug-release mechanism of poly(lactic acid) and poly[(lactic acid)-co-(glycolic acid)]. Polym. Int. 54, 36—46. 

Mathematical modelling of drug release from biodegradable systems requires consideration of the relative rates of polymer degradation and drug diffusion. Two defined scenarios may be established, as described next. 

YoUes, S., and Sartori, M. F., Degradable polymers for sustained drug release, in Drug Delivery Systems (R. L. Juliano, ed.), Oxford University Press, New York, 1980, pp. 84-111. 

The erosion of copolymers requires the hydrolytic cleavage of three bond types the A A bond, the A-B bond, and the B-B bond. If the degradation rates of these three bonds are unequal, as is likely the case, then the erosion will be inhomogeneous. And, if drugs are inhomogene-ously distributed in the polymer matrix, the drug release profile will not follow overall device erosion (Shen et al., 2002). Therefore, it is necessary to accurately describe the microstructure of microphase-separated systems. 

Crystallinity and molecular weight affect polymer degradability and consequently erosion-based release Hydrophobic drugs typically have slower release rates Increased interactions may lead to slower release High drug loading may cause increased release rates due to channeling effects... 

---