Effect of Laser-Induced Crystallinity Modification on Biodegradation Profile of Poly(L-Lactic Acid)

Abstract

Poly(L-lactic acid) (PLLA) is of interest in drug delivery applications for its biodegradable and biocompatible properties. Polymer-controlled drug delivery relies on the release of embedded drug molecules from the polymer matrix during its degradation. PLLA degradation exhibits an induction period, during which an insignificant amount of degraded products and embedded drug can be released. Due to this induction period, drug release is initially nonlinear, a complication in drug delivery applications. PLLA degradation is a function of crystallinity, such that control over its crystallinity tailors drug release over time. In this study, the effect of laser-induced PLLA crystallinity reduction on degradation is investigated. Samples having lower surface crystallinity are shown to have higher rates of molecular weight reduction and earlier mass loss than nonlasertreated samples, as observed from gel permeation chromatography and mass change. Wide-angle X-ray diffraction measurements show that crystallinity increases with degradation. A numerical model is implemented from hydrolysis and diffusion mechanisms to investigate the effect of laser irradiation on biodegradation. Controlled laser treatment of PLLA offers a method for constant drug release through the reduction of surface crystallinity.

Effect of drug loading and laser surface melting on drug release profile from biodegradable polymer

“…6 With a reduced surface crystallinity, PLA degrades faster and experiences a shorter time period before mass loss. 7 The results demonstrate the potentiality to shorten the induction period of drug release through laser crystallinity modification.…”

“…crystalline chains. 7 For 5, 10, and 20% drug loaded PLLA, the GPC profiles also shift left with time and the bimodal distributions are observed. The broadened profiles are a result of widened distribution of chain length, leading to a larger polydispersity index.…”

“…To study the effect of laser treatment on shortening the drug release induction period, the 1, 5, and 10% drug loaded matrices were treated on both sides by a KrF excimer laser with a 248 nm wavelength, 25 ns pulse width, and 3.0 J/cm 2 fluence. 7 Drug release tests were conducted such that each sample was placed in a vial and fully immersed in 10 mL phosphate buffered saline (PBS) with a pH of 7.4. The drug release period lasts for up to 84 days.…”

“…Laser energy absorbed by PLLA generates heat and is governed by the heat equation. 6,7 The process of polymer degradation and drug release is captured by a phenomenological model. In the model, PLLA matrix is assumed to be composed of nine species: nondegraded amorphous chains, degraded amorphous chains in stages 1, 2, and 3, crystalline chains, degraded crystalline chains, monomers, water molecules, and drug molecules, with details given in literature.…”

“…In the model, PLLA matrix is assumed to be composed of nine species: nondegraded amorphous chains, degraded amorphous chains in stages 1, 2, and 3, crystalline chains, degraded crystalline chains, monomers, water molecules, and drug molecules, with details given in literature. 7,15 Degradation of amorphous and crystalline chains is considered separately. During degradation, the concentration of nondegraded amorphous chain is expressed as…”