Abstract
Enoxaparin, an anticoagulant that helps prevent the formation of blood clots, is administered parenterally. Here, we report the development and evaluation of lipid–polymer hybrid nanoparticles (LPHNs) for the oral delivery of enoxaparin. The polymer poloxamer 407 (P407) was incorporated into lipid nanoparticles to form gel cores and ensure high encapsulation efficiency and the controlled release of enoxaparin. In vitro results indicated that 30% of P407 incorporation offered higher encapsulation efficiency and sustained the release of enoxaparin. Laser confocal scanning microscopy (LCSM) images showed that LPHNs could not only significantly improve the accumulation of enoxaparin in intestinal villi but also facilitate enoxaparin transport into the underlayer of intestinal epithelial cells. In vivo pharmacokinetic study results indicated that the oral bioavailability of enoxaparin was markedly increased about 6.8-fold by LPHNs. In addition, its therapeutic efficacy against pulmonary thromboembolism was improved 2.99-fold by LPHNs. Moreover, LPHNs exhibited excellent biocompatibility in the intestine. Overall, the LPHN is a promising delivery carrier to boost the oral absorption of enoxaparin.
Highlights
Heparin is an anticoagulant that prevents the formation of blood blots, and it has shown great prevention and therapeutic efficacy in terms of deep-vein thrombosis (DVT), pulmonary embolism (PE), and venous thrombosis [1] clinically
The tested amount of poloxamer 407 (P407) had no significant influence on particle size, polydispersity index, or zeta potential, but it led to different encapsulation efficiencies for enoxaparin
When the amount of P407 was set as 30%, the enoxaparin-loaded lipid–polymer hybrid nanoparticles (LPHNs) possessed a higher encapsulation efficiency of 65.72%
Summary
Heparin is an anticoagulant that prevents the formation of blood blots, and it has shown great prevention and therapeutic efficacy in terms of deep-vein thrombosis (DVT), pulmonary embolism (PE), and venous thrombosis [1] clinically. Its oral absorption is still low due to its large molecular weight, high anionic charges, and first-pass effect in the liver [4,5,6]. Because LMWH is hydrophilic, the encapsulation efficiency of LMWH in the SLNs is low, which leads to insufficient therapeutic concentration in vivo. This is due to hydrophilic drugs having limited loading quantity and homogeneity in the lipid cores. Encouraged by the advantage of SLNs and hydrogels, we attempted to fabricate lipid–polymer hybrid nanoparticles (LPHNs) for the oral delivery of enoxaparin. We attempt to investigate whether lipid–polymer hybrid nanoparticles can increase encapsulation efficiency and boost the oral absorption of enoxaparin
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