2-Dioleoyl-sn-glycero-3-phosphocholine-based nanoliposomes as an effective delivery platform for 17β-estradiol

The high loading efficiency and controlled release of hydrophobic drugs is still an unmet goal in the development of drug delivery systems. In the present study, liposomes were developed to encapsulate 17 beta-estradiol (E2), which is a sex steroid shown to confer protective effects in the cardiovascular system. Egg phosphatidylcholine (EPC), 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were used to prepare liposomes by thin film hydration and tested for their ability to load E2 with a high efficiency. DOPC-based liposomes were found to improve E2 encapsulation efficiency and loading capacity compared to those composed of EPC and DPPC. In addition, neutral liposomes, liposomes prepared with the cationic charging agent DDAB, and liposomes prepared with the anionic charging agent DMPG, were characterized with regard to their E2 encapsulation efficiency, loading capacity, particle size, zeta potential, and in vitro drug release. A human coronary artery endothelial (HCAE) cell model was used to further evaluate liposome effects on cytotoxicity and relative cellular uptake efficiency of each formulation. Results showed that DOPC liposomes composed of DDAB had the highest E2 loading capacity and improved cellular uptake compared to uncharged and DMPG-based liposomes, demonstrating the greatest potential to be used in future cardiovascular therapeutic applications. (C) 2013 Elsevier B.V. All rights reserved.