Strategy to provide a useful solution to effective delivery of dihydroartemisinin: development, characterization and in vitro studies of liposomal formulations

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2014-04, Vol.116, p.121-127
• Main Authors: Righeschi, Chiara, Coronnello, Marcella, Mastrantoni, Azzurra, Isacchi, Benedetta, Bergonzi, Maria Camilla, Mini, Enrico, Bilia, Anna Rita
• Format: Article
• Language: English
• Subjects: Albumins - chemistry; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Artemisinins - administration & dosage; Artemisinins - chemistry; Artemisinins - pharmacology; Bioavailability; Cell Proliferation - drug effects; Cell Survival - drug effects; Cellular; Computing time; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Screening Assays, Antitumor; Drugs; Flow cytometry; Formulations; Humans; Liposomes; Liposomes - chemical synthesis; Liposomes - chemistry; MCF-7 Cells; Rhodamines - pharmacology; Solutions; Structure-Activity Relationship; Tumor Cells, Cultured; Uptakes
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2013.12.019

Dihydroartemisinin is one of the most potent anticancer artemisinin-like compounds, able to induce cancer cell death by apoptotic pathways. Besides its effectiveness, it is a poorly water soluble drug with low bioavailability and low half-life (34-90 min), therefore, the development of new formulations of dihydroartemisinin to increase bioavailability is in great need. Conventional (P90G and cholesterol) and stealth liposomes (P90G; cholesterol and PE 18:0/18:0 PEG 2000) to deliver dihydroartemisinin to cancer cells were developed for the first time. Both developed formulations show physical characteristics as drug carrier for parental administration and good values of encapsulation efficiency (71% conventional liposomes and 69% stealth liposomes). Physical and chemical stabilities were evaluated under storage condition and in presence of albumin. Cellular uptake efficiency of liposomes was determined by flow cytometry. Higher internalization occurred in the conventional liposomes rather than in the stealth liposomes suggesting that hydrophilic steric barrier of PEG molecules can reduce cellular uptake. Flow cytometry analysis was also used as an alternative technique for rapid size determination of liposomes. Cytotoxicity studies in the MCF-7 cell line confirmed the absence of toxicity in blank formulations suggesting liposomes may be a suitable carrier for delivery of DHA avoiding the use of organic solvents. Cytotoxicity of DHA and of both liposomal formulations was evaluated in the same cell line, confirming a modified release of DHA from vesicles after cellular uptake.