Development of sodium alginate nanocarriers for the treatment of ophthalmic infection and inflammation

Abstract

Limited bioavailability of the current eye drops caused by insufficient corneal penetration and quick drug washout often leads to the requirement of frequent doses during the treatment of ophthalmic diseases. In this study, sodium alginate polymannuronate (SA) nanocarriers were prepared using ionotropic gelation method to provide better bioavailability through mucoadhesivity by binding to the ocular mucus layer. It has been assumed till this date that only G blocks of SA takes part in ionic crosslinking. This study has revealed that M blocks can also take part in crosslinking during ionic gelation in the absence of G blocks and show better encapsulation efficiency due to self-assembly. This comprehensive analysis of the only M block containing sodium alginate (SA) nanoparticles demonstrated how to modify their properties by meticulously choosing the appropriate crosslinker type and concentration, and also highlighted their novel drug delivery behavior. Four crosslinkers were initially studied at various concentrations and the Taguchi design of experiment demonstrated that the crosslinker type and concentration had a statistically significant effect on particle size and stability. By comparing the zeta potential and particle size values, the optimal combination with the necessary microstructural characteristics for the research purpose was found. Dexamethasone (DEX) and Ciprofloxacin (CIP) were loaded into the nanoparticles. Polymeric micelles formed through self-assembly of the polymer showed very high encapsulation efficiency upon the incorporation of the two hydrophobic drugs. Sustained and simultaneous release of the drugs was obtained. The formulation was proved to be biocompatible and cured the scleral inflammation of the rabbit uveitis models significantly within only 3 days. However, semi-gel formulationsare frequently sticky, opaque, and too viscous to use comfortably. Thus, a nanosuspension based formulation is required to be prepared for overcoming the issues while maintaining the beneficial qualities of the semi-gel.Thus, nanosuspension has been formulated mimicking human tear fluid properties.It is expected that this in-depth study will pave the way for future works using the nanocarriers, in the field of targeted drug and protein delivery.