Rifampicin-loaded phthalated cashew gum nano-embedded microparticles intended for pulmonary administration

Tuberculosis is a serious infectious disease commonly treated with rifampicin (RIF), which has low water solubility and high permeability. Polymeric nanoparticles (PNs) are used for controlled drug delivery to improve drug efficacy. However, PNs can be easily expelled via pulmonary administration. Nano-embedded microparticles (NEMs) are designed to bypass pulmonary barriers. Cashew gum, a versatile heteropolysaccharide, was modified into phthalated cashew gum (PCG), which targets alveolar macrophages, to increase hydrophobicity and improve drug encapsulation efficiency. In this study, the PCG was successfully obtained. Polymeric nano- particle (PN)-PCG-RIF was fabricated, and its performance characteristics were investigated. PN-PCG-RIF exhibits mucoadhesive properties. An in vitro release study showed the release of 66.57 % of RIF after 6 h. An in vitro cytotoxicity study in A549 cells showed that PN-PCG-RIF is cytocompatible. The cellular uptake study demonstrated efficient cellular internalization in J774 macrophages, which was attributed to the PCG composition binding to the galactose-type lectin C receptor (MGL-2/CD301b). NEM-RIF was optimized by the Box Behnken designer with a particle size of 240.80 nm, PdI of 0.185, and redispersion index of 1.63. Scanning electron microscopy revealed NEMs-RIF in the form of spherical agglomerates. Collectively, RIF-NEMs were successfully developed from PN-PCG-RIF, having potential for the treatment of tuberculosis.