Reverse biomembrane vesicles for effective controlled delivery of doxorubicin HCl

A new derivative of erythrocyte ghosts--reverse biomembrane vesicles (RBVs)--was developed, loaded with doxorubicin HCl (Dox RBVs), and extensively characterized both in vivo and in vitro. The formulation of reverse biomembrane is based on budding of membrane into the ghost interiors (endocytosis) leading to accumulation of small vesicles within each parent ghost. The system was evaluated in vitro for entrapment efficiency, membrane orientation, vesicle size, release profile, and centrifugal stress. The stability studies were performed at 4 degrees C by assessing the effect on vesicle size and leakage after 7, 15, and 21 days. The stability study showed negligible leakage and no appreciable change in vesicle size after storage for several days--an indication of good stability of RBVs formulation. The formulation and process variables were optimized to obtain vesicles of 1.2-1.8 microm. The amount of doxorubicin entrapped in RBVs was 0.75 mg/ml of packed vesicles. The in vitro release profile showed 52.86% of drug release in 16 hr. A membrane orientation study revealed inversion of membrane surface because only 10% of sialic acid was accessible on trypsin treatment. The plasma clearance data revealed an increase in half-life and bioavailability of drug. Tissue concentration data suggest that liver and spleen remain the major organs for clearance of these drug-loaded RBVs, which suggests preferential uptake by the reticuloendothelial system. On the whole, this vesicle system proved to be of potential application in cancer chemotherapy.