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

6533b855fe1ef96bd12affee

RESEARCH PRODUCT

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

Gaetano Giammona Massimo Fresta Christian Celia Christian Celia Gennara Cavallaro Mariano Licciardi Donato Cosco Nicolò Mauro Donatella Paolino

subject

Drug Biodistribution Macromolecular Substances media_common.quotation_subject Supramolecular chemistry Antineoplastic Agents 02 engineering and technology 010402 general chemistry Hydrazide Deoxycytidine 01 natural sciences Biochemistry Gemcitabine Hydrochloride supramolecular chemistry Structure-Activity Relationship chemistry.chemical_compound Drug Delivery Systems Cations Drug Discovery Tumor Cells Cultured Animals Humans Tissue Distribution Cationic liposome Rats Wistar General Pharmacology Toxicology and Pharmaceutics vesicular aggregates Cell Proliferation media_common Pharmacology Liposome Dose-Response Relationship Drug Molecular Structure nanoparticle Organic Chemistry Cationic polymerization 021001 nanoscience & nanotechnology Gemcitabine Rats 0104 chemical sciences chemistry Biochemistry antitumor agent liposome Molecular Medicine Drug Screening Assays Antitumor 0210 nano-technology

description

The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) 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 (A549) and colorectal cancer (CaCo-2) cells. GEM-loaded cationic SVAs increased the anticancer activity in A549 and CaCo-2 cells relative to free drug, neutral SVAs, and CLs. In vivo biodistribution in Wistar rats showed that cationic SVAs accumulate at higher concentrations in lung tissue than neutral SVAs and CLs. Cationic SVAs may therefore serve as an innovative future therapy for pulmonary carcinoma.

year	journal	country	edition	language
2016-03-08	ChemMedChem

https://doi.org/10.1002/cmdc.201600070