Alginate coated chitosan microparticles mediated oral delivery of diphtheria toxoid. (Part A). Systematic optimization, development and characterization

The current study was embarked upon to develop “optimized” alginate coated chitosan microparticles (ACMs) loaded with Diphtheria toxoid (DTx) employing formulation by design approach. The developed system was characterized for particle size, zeta potential, surface morphology, acidic degradation protection studies, in process stability studies, storage stability studies and in-vivo uptake studies. Microparticles with minimum of average size of 5 μm (PDI, 0.184) were chosen after optimizing the composition and process conditions. The optimized chitosan microparticles were subjected to alginate coating for better protection of loaded antigen till it reached to uptake site i.e. M cells in the Peyer's patches (PPs) and transport of higher amount antigen to the PPs. The zeta-potential values for uncoated chitosan microparticles and ACMs were found to be +29 ± 3.3 mV and −32.6 ± 4.2 mV, respectively. This change of zeta potential, for uncoated to coated, can be explained by the fact that the coating of alginate on chitosan microparticles led to negative side of the zeta potential by virtue of its predominance on the surface. The developed ACMs were able to transport the antigen effectively to the M cell as revealed by confocal laser scanning microscopy. Further, DTx-loaded ACMs demonstrated significant immune responses at serum IgG as well as mucosal sIgA level.

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