Morphology and Release Kinetics of Protein-Loaded Porous Poly(L-Lactic Acid) Spheres Prepared by Freeze-Drying Technique

Takashi Sasaki,Daisuke Morino,Kazuki Tanaka,Kensuke Sakurai

doi:10.5402/2011/490567

Abstract

Freeze-drying a biodegradable polymer, poly(L-lactic acid) (PLLA), from 1,4-dioxane solutions provided very porous spherical particles of ca. 3 mm in radius with specific surface area of 8–13 m2 g−1. The surface of the particle was found to be less porous compared with its interior. To apply the freeze-dried PLLA (FDPLLA) to drug delivery system, its morphology and drug releasing kinetics were investigated, bovine serum albumin (BSA) being used as a model drug compound. Immersion of FDPLLA into a BSA aqueous solution gave BSA-loaded FDPLLA, where mass fraction of the adsorbed BSA reached up to 79%. Time-dependent release profile of BSA in water suggested a two-step mechanism: (1) very rapid release of BSA deposited on and near the particle surface, which results in an initial burst, and (2) leaching of BSA from the interior of the particle by the diffusion process. It was suggested that the latter process is largely governed by the surface porosity. The porosity of both the interior and surface was found to decrease remarkably as the concentration of the original PLLA/1,4-dioxane solution increases, C 0. Thus, C 0 is a key parameter that controls the loading and releasing of BSA.

Highlights

In recent decades, controlled drug release from capsules made from biodegradable and biocompatible polymers has been extensively studied
We confirmed by differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS) that the as-prepared freeze-dried PLLA (FDPLLA) is completely amorphous as we reported elsewhere [20]
We have found that the porosity and specific surface area of the present FDPLLA are rather high, which leads to prominent ability of protein loading

Summary

Introduction

In recent decades, controlled drug release from capsules made from biodegradable and biocompatible polymers has been extensively studied. The drug release from microspheres are considered to occur both by degradation of the polymer matrix and by simple diffusion of the drug molecules. It has been revealed that various factors affect the feature of drug release, such as the size and structure of the microsphere, porosity, chemistry, degradability, and molar mass of the polymer material, and pH value of the medium [1]. Microspheres for the drug release have been prepared by polymerization method or by solvent removing method [1]. Controlled/living radical polymerization, which has been developed recently, can provide microspheres with well-controlled morphology [6]. For biodegradable polymers such as poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA), and various naturally occurring polymers, microspheres are usually prepared by solvent evaporation or spray-drying method [7,8,9,10,11,12,13,14,15,16,17]

Methods

Results

Conclusion