2013 Theses Doctoral

Effect of Laser Induced Crystallinity Modification on Degradation and Drug Release of Biodegradable Polymer

Hsu, Shan-Ting

Biodegradable polymers such as poly(L-lactic acid) (PLLA) are promising in drug delivery applications. In biodegradable polymer-based drug delivery systems, drugs are released at a rate determined by polymer degradation. Polymer degradation exhibits an undesirable induction period, during which a limited amount of embedded drug is released. As a semi-crystalline polymer, PLLA degradation and drug release are affected by its crystallinity. Control over PLLA crystallinity tailors drug release over time, and provides a potential solution to shorten the induction period of polymer degradation and drug release.The work presented in this thesis first investigates the crystalline morphology and crystallinity developed during the PLLA film formation processes. Solvent casting, spin coating, and subsequent annealing are conducted. The resulting morphology, crystallinity, molecular order, conformation, and intermolecular interaction are examined using optical microscopy, wide-angle X-ray diffraction, and Fourier transform infrared spectroscopy. Solvent casting produces category 1 spherulites, and annealing the spin coated films leads to category 2 spherulites. Crystal structure of the two kinds of films shows distinct features. The results advance the understanding of PLLA crystal structures, which is essential for its medical applications.Control over crystallinity allows for modification of PLLA degradation and drug release over time. Laser irradiation is used in this study to induce surface melting and resolidification. The high cooling rate of the laser treatment coupled with the slow polymer crystallization kinetics leads to reduced surface crystallinity after the laser irradiation. Effects of laser irradiation on the surface morphology, crystallinity, and chemical modifications are investigated via optical microscopy, wide-angle X-ray diffraction, and X-ray photoelectron spectroscopy. The effect of laser crystallinity modifications and drug loading concentration on PLLA biodegradation and drug release is investigated. Degradation is characterized through molecular weight by gel permeation chromatography. Drug release is measured by spectrophotometry. A finite element model is developed to numerically examine the spatial and temporal temperature profiles, as well as chemical modifications in the PLLA matrix after the laser treatment. Effect of laser crystallinity modification on biodegradation and drug release is also numerically investigated based on PLLA hydrolysis and diffusion mechanisms. It has been demonstrated that laser irradiation reduces PLLA crystallinity. A working window of laser fluence levels exists within which crystallinity is decreased while no appreciable chemical modification is observed. The working window is enlarged for the higher crystalline polymer as a result of the cage effect. The degradation and drug release tests show that the addition of drug accelerates polymer degradation and drug release rate, because the porous structure after drug release favors water penetration and hydrolysis based degradation. With a low drug concentration, the slow polymer degradation kinetics results in an induction period of drug release. The induction period is shortened by the laser treatment. It is demonstrated that laser treated PLLA, with lower surface crystallinity, has a higher initial degradation rate while the subsequent degradation is not modified. Because of the accelerated initial degradation, the induction period of drug release is therefore shortened, while the drug release rate is kept unmodified, which is desired in drug delivery applications.