Novel Nanoparticles for the Oral Delivery of Low Molecular Weight Heparin: In Vitro and in Vivo Assessment

Abstract

Objective: The objective of the present study was to prepare and evaluate a novel oral formulation of nanoparticles for the systemic delivery of lowmolecular-weight heparin (LMWH).Methods: Nanoparticles were prepared by polyelectrolyte complexation method using polymers, i.e., sodium alginate and chitosan (CH). Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency, In vitro release and scanning electron microscopic studies were carried out for nanoparticles. Ex vivo permeation studies were performed with optimized formulation using small intestine of rat and in vivo studies were conducted on rat model. Results:Entrapment efficiency of LMWH in nanoparticles was found to be 88%. 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 CH interacted with the carboxylic groups of alginate. In vitro % drug release of 95% was shown by formulation AC5. Ex vivo permeation studies have elucidated that ~73% of LMWH was transported across the epithelium. Nanoparticles have shown enhanced oral bioavailability of LMWH as revealed by 4.5-fold increase in area under the curve of plasma drug concentration-time curve. Conclusion:The results suggest that the nanoparticles prepared can result in targeted delivery of LMWH into systemic circulation through intestinal and colon routes. Novel nanoparticles thus prepared in this study can be considered as a promising delivery system.

Unsuccessful Delivery of Tetrandrine From Colon-Targeted Dosage Forms Comprising Alginate/Hydroxypropyl Methylcellulose and Alginate–chitosan Beads

“…The viscosity of alginate/HPMC mixtures affected the diameters and densities of beads and the volumes of entrapped drug substance. Alginate-chitosan beads increased in diameter with increasing chitosan concentrations, reflecting the formation of polyelectrolyte complexes between carboxyl groups of alginate and amine groups of chitosan [31][32][33][34]. Previous studies have shown that bead sizes are normally distributed over 50-2000 µm [35].…”

Synthesis and Stability of Resveratrol-Conjugated Gold Nanoparticles Modified With Polyethylene Glycol

“…Nanoparticles are usually <100 nm in size. They consist of different biodegradable materials such as natural or synthetic polymers, lipids, or metals [2]. Gold nanoparticles (AuNPs) have been widely developed as a multifunctional platform for various biomedical applications [3] such as biosensing systems, cancer therapies, drug delivery, and pharmaceuticals [4].…”

Synthesis and Stability of Resveratrol-Gold Nanoparticle-Polyethylene Glycol-Folic Acid Conjugates

“…Nanoparticles have several advantages, such as improvement in the intracellular infiltration, circulation time of the drug, and enhanced hydrophobic solubility [1]. They consist of different biodegradable materials such as natural or synthetic polymers, lipids, or metals [2]. Gold nanoparticles (AuNPs) are some of the most widely employed nanoparticles in medicine.…”