Cell-Penetrating Peptide-Surface Modified Liposomes to Enhance the Intestinal Absorption of Enoxaparin

Abstract

Background: Enoxaparin is low-molecular-weight heparin administered by subcutaneous/intravenous injection. The oral bioavailability of enoxaparin is restricted by its low absorption through the intestine. In this study cell-penetrating peptide-surface functionalized liposomes (CPPs-L) were prepared to improve the intestinal absorption of enoxaparin. Methods: Liposomal formulations were prepared by the ethanol injection method and the intestinal absorption of the formulation was evaluated using the single-pass intestinal perfusion (SPIP) technique in rats. Meanwhile, the human fraction dose absorbed value (Fa (human)) of the formulations was predicted based on the calculated effective intestinal permeability (P effect (rat)) values obtained from the SPIP study. Results: Liposomal enoxaparin revealed an increased intestinal absorption by ten-time compared with the free drug solution. Meanwhile, CPPs-L formulation revealed an enhanced intestinal absorption compared with the un-modified liposomal formulation. Regarding Fa (human), it is predicted that liposomal formulations could have the potential to improve the fraction dose absorbed of enoxaparin from low to intermediate levels. Conclusion: Overall, the liposomal formulation can be considered as a mighty drug carrier for the oral delivery of enoxaparin.

Keywords

• cell-penetrating peptide
• enoxaparin
• intestinal absorption
• liposome