Polymeric micelles coated with hybrid nanovesicles enhance the therapeutic potential of the reversible topoisomerase inhibitor camptothecin in a mouse model.

Abstract

Nanoparticles with longer blood circulation, high loading capacity, controlled release at the targeted site, and preservation of camptothecin (CPT) in its lactone form are the key characteristics for the effective delivery of CPT. In this regard, natural membrane-derived nanovesicles, particularly those derived from RBC membrane, are important. RBC membrane can be engineered to form vesicles or can be coated over synthetic nanoparticles, without losing their basic structural features and can have prolonged circulation time. Here, we developed a hybrid system to encapsulate CPT inside the amphiphilic micelle and coat it with RBC membrane. Thus, it uses the dual ability of polymeric micelles to preserve CPT in its active form, while maintaining its "stealth" effect due to conserved RBC membrane coating. The hybrid system stabilized 60% of the drug in its active form even after 30 h of incubation in serum, in contrast to 15% active form present in free drug formulation after 1 h of incubation. It showed strong retention inside the Ehrlich Ascites Carcinoma (EAC) mice models for at least 72 h, suggesting camouflaging ability conferred by RBC membrane. Additionally, the nano formulation retarded the tumor growth rate more efficiently than free drug, with no evident signs of necrotic skin lesions. Histopathological analysis showed a significant reduction in cardiac atrophy, hepato-renal degeneration, and lung metastasis, which resulted in the increased overall survival of mice treated with the nano formulation. Hence, CPT-loaded polymeric micelles when coated with RBC membrane can prove to be a better system for the delivery of poorly soluble drug camptothecin.