A novel approach to prepare tripolyphosphate/chitosan complex beads for controlled release drug delivery

Abstract

A novel approach was developed to improve the mechanical strength of tripolyphosphate (TPP)/chitosan beads prepared under coagulation condition at 4°C in the presence of gelatin. Cross-sectional analysis indicated that the beads had a homogeneous crosslinked structure, as a result the beads were strengthened greatly (the mechanical strength increased more than ten times). Furthermore sodium alginate (a polyanion) can interact with cationic chitosan on the surface of these TPP/chitosan beads to form polyelectrolyte complex film for the improvement of the drug sustained release performances. The loading efficiency of model drugs (brilliant blue and FITC-dextran) in these beads was very high (more than 90%). Crosslinking time, TPP solution pH and other preparation factors had an effect on the drug release performance of beads. The release period of brilliant blue (a poor water soluble dye) was more than 2-months at a fairly constant rate in 0.9% NaCl, 10 mM PBS pH 7.4. However, for FITC-dextran (a water soluble polysaccharide) only 1–2 days in the same conditions. It seems that TPP/chitosan bead prepared by the novel method is a promising formulation for drug delivery.

Introduction

Chitosan with excellent biodegradable and biocompatible characteristics, is a naturally occurring polysaccharide. Due to its unique polymeric cationic character and its gel and film forming properties, chitosan has been examined extensively in the pharmaceutical industry for its potential in the development of drug delivery systems (Yao et al., 1995, Illum, 1998).

Recently, the use of complexation between oppositely charged macromolecules to prepare chitosan beads (or microspheres) as a drug controlled release formulation, especially for peptide and protein drug delivery, has attracted much attention, because this process is very simple and mild (Polk et al., 1994, Liu et al., 1997). In addition, reversible physical crosslinking by electrostatic interaction, instead of chemical crosslinking, is applied to avoid possible toxicity of reagents and other undesirable effects.

Tripolyphosphate (TPP) is a polyanion, and can interact with cationic chitosan by electrostatic forces (Kawashima et al., 1985a, Kawashima et al., 1985b). Since Bodmeier et al. (1989) reported a TPP/chitosan complex can be prepared by dropping chitosan droplets into a TPP solution, many workers have explored the potential pharmaceutical usage (Shirashi et al., 1993, Sezer and Akbuga, 1995, Aydin and Akbuga, 1996, Calvo et al., 1997a, Calvo et al., 1997b, Shu and Zhu, 1999). However, the mechanical strength of these chitosan beads is very poor, so its usage in the pharmaceutical industry is still limited.

Aral and Akbuga (1998) have strengthened TPP/chitosan beads by coating sodium alginate on the bead surface to form a polyelectrolyte complex film. But the poor mechanical strength of TPP/chitosan beads still needs to be improved. Herein we report a new method to prepare TPP/chitosan beads with a more homogeneous structure. The controlled release behavior of model drugs from these beads was also investigated.