NOVEL NANOPARTICLES FOR THE ORAL DELIVERY OF LOW MOLECULAR WEIGHT HEPARIN: IN VITRO AND IN VIVO ASSESSMENT
Objective: The objective of the present study was to prepare and evaluate a novel oral formulation of nanoparticles for the systemic delivery of low molecular weight heparin (LMWH).
Â Methods: Nanoparticles were prepared by polyelectrolyte complexation (PEC) method using polymers sodium alginate and chitosan. Entrapment efficiency of LMWH in nanoparticles was found to beÂ Ì´88%. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), Xâ€‘ray diffraction (XRD), Scanning electron microscopy (SEM) Â studies carried for nanoparticles. In vitro release studies were performed for the formulations. Ex vivo permeation studies were performed optimized formulation by using small intestine of rat and in vivo studies were conducted on rat model.
Results: In vitro release studies demonstrated that the release of LMWH was negligible in the stomach and high in the small intestine. FTIR has indicated that there is no interaction between the ingredients in nanoparticle. DSC and XRD studies confirmed that the amino groups of chitosan interacted with the carboxylic groups of alginate. Invitro % drug release of 95% was shown by formulation AC5. Ex vivo permeation studies have elucidated that Ì´ 73% of LMWH was transported across the epithelium. Nanoparticles have shown enhanced oral bioavailability of LMWH as revealed by 4.5 fold increase in AUC of plasma drug concentration time curve.
Conclusion: The results suggest that the nanoparticles prepared can result in targeted delivery of LMWH into systemic circulation via intestinal and colon routes. Novel nanoparticles thus prepared in this study can be considered as a promising delivery system.
Keywords: Antifactor Xa activity, Chitosan, Differential scanning calorimetry, Sodium alginate, Low-molecular-weight heparin, Oral bioavailability.
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