Student United Institute of Pharmacy Kanpur, Uttar Pradesh, India
Background: Objective of present study was to enhance oral bioavailability of anticoagulant drug by polymeric nanoparticulate carrier system. Low Molecular Weight Heparins(LMWH) are administered by parenteral route and repetitive injections are disadvantages which demand for an improvement of administration strategy by other non-invasive routes. It can be replaced by oral warfarin for outpatient therapy but it has slow onset and high incidence of drug–drug interaction.
Aims: Oral route is most convenient administration pathway highly accepted by all patients but it presents a challenge owing to large anionic charge, excessive hydrophilicity and high molecular weight of drug thus depicting poor absorption. Due to these limitations to oral delivery of LMWH, different approaches such as carriers or absorption promoters have been proposed to enhance oral absorption.
Methods: Chitosan nanoparticles(NPs) were prepared by ionic gelation of chitosan and coated with alginate solution. NPs were characterized for morphology, particle size, polydispersity index, zeta potential, drug loading and entrapment efficiency using SEM, Zeta-sizer, FTIR and DSC. In-vitro release and permeation study was performed, in-vivo studies included venous thrombosis model, uptake using fluorescence microscopy and pharmacokinetic studies in rats.
Results: Coating of alginate over NPs improved release profile of enoxaparin from nanoparticles for successful oral delivery. In-vitro permeation studies elucidated that more amount of drug permeated across intestinal epithelium due to alginate coating. In-vivo studies show enoxaparin loaded nanoparticles exhibit better anticoagulant activity during oral administration. Results of present study indicated that this system is more stable as compared to other system.
Conclusion(s): Enoxaparin loaded alginate coated chitosan nanoparticulate carrier was developed and showed enhanced drug stability, improved availability across intestine, reduced thrombus formation in rat venous thrombosis model along with reduced side effects as compared to drug solution. These results concluded that designed nanocarriers as possible candidates for improving absorption of low molecular weight heparin by oral administration.
