Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy.
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.
Laboratory of Biocompatible Polymers, Biological, Chemical and Pharmaceutical Sciences and Technologies Department (STEBICEF), University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.
Mariano
M
Licciardi
Department of Experimental and Clinical Medicine, Building of BioSciences, University of Catanzaro "Magna Graecia", V.le Europa s.n.c., 88100, Germaneto, Italy.|Interregional Research Center for Food Safety & Health (IRCFSH), Building of BioSciences, University of Catanzaro "Magna Graecia", V.le Europa s.n.c., 88100, Germaneto, Italy.
Donatella
D
Paolino
Laboratory of Biocompatible Polymers, Biological, Chemical and Pharmaceutical Sciences and Technologies Department (STEBICEF), University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.
Nicolò
N
Mauro
Interregional Research Center for Food Safety & Health (IRCFSH), Building of BioSciences, University of Catanzaro "Magna Graecia", V.le Europa s.n.c., 88100, Germaneto, Italy.|Department of Health Sciences, University of Catanzaro "Magna Graecia", Building of BioSciences, V.le Europa s.n.c., 88100, Germaneto, Italy.
Donato
D
Cosco
Laboratory of Biocompatible Polymers, Biological, Chemical and Pharmaceutical Sciences and Technologies Department (STEBICEF), University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.|Mediterranean Center for Human Advanced Biotechnologies (Med-Chab), Viale delle Scienze Ed. 18, 90128, Palermo, Italy.
Gaetano
G
Giammona
Interregional Research Center for Food Safety & Health (IRCFSH), Building of BioSciences, University of Catanzaro "Magna Graecia", V.le Europa s.n.c., 88100, Germaneto, Italy.|Department of Health Sciences, University of Catanzaro "Magna Graecia", Building of BioSciences, V.le Europa s.n.c., 88100, Germaneto, Italy.
Massimo
M
Fresta
Laboratory of Biocompatible Polymers, Biological, Chemical and Pharmaceutical Sciences and Technologies Department (STEBICEF), University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.
Gennara
G
Cavallaro
Department of Pharmacy, University of Chieti - Pescara "G. d'Annunzio", Via dei Vestini 31, 66100, Chieti, Italy. c.celia@unich.it.|Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA. c.celia@unich.it.
Christian
0000-0002-0590-5429
C
Celia
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D046911:Macromolecular Substances / Q000008:administration & dosage* / Q000737:chemistry*; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D002412:Cations; D046911:Macromolecular Substances; D003841:Deoxycytidine; D000093542:Gemcitabine
antitumor agents; liposomes; nanoparticles; supramolecular chemistry; vesicular aggregates