Design and development of a novel controlled release PLGA alginate-pectinate polyspheric drug delivery system

Abstract

A 23 full factorial design was employed to evaluate and optimize the drug entrapment efficiency and in vitro drug release from PLGA microparticles encapsulated in a complex crosslinked alginate-pectinate matrix (polysphere). The independent formulation variables included the volume of internal and external phases, and concentration of PLGA. Surface morphology and internal structure of PLGA microparticles and polyspheres were examined by scanning electron microscopy which revealed spherical PLGA microparticles with highly porous surfaces that accounted for the rapid burst effect of this system. Texture analysis was used to profile the matrix resilience, tolerance, and energy absorbed. In vitro drug release was assessed in buffer media on PLGA microparticles and polyspheres. Polyspheres exhibited ideal zero-order release while PLGA microparticles had a burst effect followed by lag phase. Kinetic modeling of in vitro drug release data indicated that formulations were not highly dependent on polymeric erosion as a mechanism for drug release but rather diffusion. A close correlation existed between the matrix tolerance and energy absorbed. Formulations with decreased tolerance absorbed less energy, thus led to rapid surface erosion, lower matrix integrity and hence a burst effect. The converse was true for an increased matrix tolerance, which led to zero-order release supported by superior matrix integrity and a significantly reduced burst effect. The rat subcutaneous model validated in vitro release data and demonstrated that the polyspheres provided flexible yet superior rate-modulated drug delivery.