title: Transdermal delivery of low molecular weight heparin loaded in flexible liposomes with bioavailability enhancement: comparison with ethosomes.
abstract: Low molecular weight heparin (LMWH)-loaded flexible liposomes (flexosomes) were formulated for transdermal delivery, and their physicochemical and pharmacokinetic parameters were compared with LMWH-loaded ethosomes. Flexosomes had similar particle size compared with ethosomes, but their deformability was higher than that of ethosomes (76.7% vs. 46.8%). In vitro, flexosomes demonstrated 2.6-fold higher permeability coefficient than ethosomes. In comparison to LMWH aqueous solution, skin deposition of flexosome increased 3.2-fold, while that of ethosome increased only 2.0-fold. In vivo, after the topical application of flexosome to hairless mouse, [anti-Xa](max) was 1.11 IU/mL, while ethosomes showed only 0.32 IU/mL. Moreover, AUC(0-24 h) of flexosomes was 2.5-fold higher than ethosomes. In conclusion, the enhanced skin permeation and bioavailability of LMWH can be achieved with flexosomes in comparison with ethosomes. The LMWH transdermal delivery via flexosomes has the potential to replace the parenteral dosage forms for the treatment of venous thromboembolism, pulmonary embolism and cardiovascular events.
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Yun-Kyoung
authors.initials: YK
authors.lastname: Song
authors.forename: Seo Yeon
authors.initials: SY
authors.lastname: Hyun
authors.forename: Hyung-Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Chong-Kook
authors.initials: CK
authors.lastname: Kim
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Oh
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008081:Liposomes; D051379:Mice; D011655:Pulmonary Embolism / Q000188:drug therapy; D013923:Thromboembolism / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008081:Liposomes