Externally Triggered Novel Rapid-Release Sonosensitive Folate-Modified Liposomes for Gemcitabine: Development and Characteristics

• Published in: International journal of nanomedicine Vol. 16; pp. 683 - 700
• Main Authors: Omar, Mahmoud M, Hasan, Omiya Ali, Zaki, Randa Mohammed, Eleraky, Nermin E
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Apoptosis; Cancer; Cancer therapies; Carboplatin; Care and treatment; Cell Death - drug effects; Cell Line, Tumor; Chemotherapy; Cholesterol; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxycytidine - blood; Deoxycytidine - pharmacokinetics; Deoxycytidine - pharmacology; Deoxyribonucleic acid; DNA; DNA repair; Drug Delivery Systems; Drug Liberation; Drugs; Endocytosis - drug effects; Ethylenediaminetetraacetic acid; Female; folate-modified liposomes; Folic acid; Folic Acid - chemistry; Gemcitabine; Humans; Kinases; Lipids; Liposomes; Original Research; Ovarian cancer; Ovarian Neoplasms - blood; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Particle Size; Polyethylene glycol; Rats; Rats, Sprague-Dawley; sonosensitive liposome; that externally triggered; Tissue Distribution - drug effects; Tumors; Ultrasonics; Egypt; folate-modified liposomes; sonosensitive liposome; gemcitabine; ovarian cancer; externally triggered
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S266676

To develop an externally triggered rapid-release targeted system for treating ovarian cancer, gemcitabine (GMC) was entrapped into sonosensitive (SoS) folate (Fo)-modified liposomes (LPs). GMC-loaded LPs (GMC LPs), GMC-loaded Fo-targeted LPs (GMC-Fo LPs), and GMC-loaded Fo-targeted SoS LPs (GMC-SoS Fo LPs) were prepared utilizing a film-hydration technique and evaluated based on particle size, ζ-potential, and percentage entrapped drug. Cellular uptake of the fluorescent delivery systems in Fo-expressing ovarian cancer cells was quantified using flow cytometry. Finally, tumor-targeting ability, in vivo evaluation, and pharmacokinetic studies were performed. GMC LPs, GMC-Fo LPs, and GMC-SoS Fo LPs were successfully prepared, with sizes of <120.3±2.4 nm, 39.7 mV ζ-potential, and 86.3%±1.84% entrapped drug. Cellular uptake of GMC-SoS Fo LPs improved 6.51-fold over GMC LPs (under ultrasonic irradiation - <0.05). However, cellular uptake of GMC-Fo LPs improved just 1.24-fold over GMC LPs ( >0.05). Biodistribution study showed that of GMC concentration in tumors treated with GMC-SoS-Fo LPs (with ultrasound) improved 2.89-fold that of free GMC ( <0.05). In vivo, GMC-SoS Fo LPs showed the highest antiproliferative and antitumor action on ovarian cancer. These findings showed that externally triggered rapid-release SoS Fo-modified LPs are a promising system for delivering rapid-release drugs into tumors.