Biosynthetic polyhydroxyalkanoates and their potential in drug delivery

Abstract

Polyhydroxyalkanoates (PHAs) are naturally occurring biodegradable polyesters produced as energy storage materials by many bacteria. The most common PHA, poly(3-hydroxybutyrate) (PHB), can be produced in high yield by fermentation of a variety of bacterial strains. PHB is a isotactic semi-crystalline polyester with great potential as a biodegradable commodity; it has useful physico-mechanical properties and appears to be biocompatible. Hydrolytic degradation occurs by surface erosion which makes it an attractive material for controlled release applications. The homopolymer PHB has a relatively high melting point and crystallizes rapidly, making entrapment of drug technically difficult. The related copolymers with 3-hydroxyvalerate, P(HB-HV)s, have similar semi-crystalline properties though their slower rates of crystallization result in matrices with different properties; this merits further investigation. Release of low molecular weight drugs from PHB and P(HB-HV) matrices tends to proceed by penetration of water and pore formation, at least above loadings of approximately 5% drug. Release from such matrices is predominantly independent of polymer erosion; though at lower loadings it is possible to trap drug more effectively. PHB and P(HB-HV) matrices lose mass very slowly when compared to bulk-degrading poly(lactide-glycolide) systems. Therefore the applications of these materials in drug delivery are likely to depend on the formulation of suitable blends with other biocompatible polymers. Porosity, erosion rate and hence drug release rate can be controlled by blending techniques. At a more fundamental level there is considerable potential for design and bioengineering of other PHAs for applications in drug delivery. For example, medium chain PHAs are rubbery materials with low melting points which may be much more suitable as matrices for applications in drug delivery.