Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy

The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regards to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of polyasparthylhydrazide by thin layer evaporation and extrusion techniques. Both copolymers were self-assembled in pre-formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100 nm. The anticancer activity of GEM-loaded neutral and cationic SVAs was tested in human alveolar basal epithelial (AS-49) and colorectal cancer (Ca-Co-2) cells. In vivo biodistribution in Wistar rats showed that cationic SVAs accumulate at higher concentration in lung tissue than neutral SVAs and CLs. Cationic SVAs may therefore serve as an innovative future therapy for pulmonary carcinoma.