Immunomodulating polyorganophosphazene-arginine layered liposome antibiotic delivery vehicle against pulmonary tuberculosis

Tuberculosis (TB) is an infectious disease that leads to high mortality and remains challenging because of the poor treatment efficiency and side effects. The multifunctional poly(organo)phosphazene with arginine to overcome the challenges via immunomodulating properties. Polymer grafted liposomes enhance the delivery of both drugs in the tuberculosis-infected alveolar macrophages. It also effectively triggers macrophage cell proliferation, nitric oxide production and activates innate responses against pathogens. The thin-film method was used to prepare three different liposome designs. And, suitable liposome formulation was selected for coating by the arginine-g-PCPP polymer. The breakdown of ester bonds under the acidic condition helps to drug releases inside the cell. In the endosomal pH condition, the release of RIF and IZN was 73 and 80%. The neutral pH release of RIF and IZN was 57 and 62%. PGL drug delivery system will improve the antibacterial activity against both gram-positive and gram-negative bacteria. Dual drug-loaded PGL shows a higher inhibitory of Mycobacterium at 2 mg/mL. It was four times less concentrated compared to the single drug-loaded PGL. It also accelerates macrophage cell proliferation via m -CSF and CAT-1. Our results indicate that PGL can deliver dual drugs to the TB-infected macrophage and modulate the immune system against TB pathogens.