Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex.

Xiao-Lei Qiu,Chun-Xia Li,Shi-Xin Wang,Zi-Rui Fan,Ding-Fu Wang,Yang-Yang Liu

doi:10.3390/ijms22084077

Abstract

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.

Highlights

Unfractionated heparin (UFH) is a natural and widely used anticoagulant drug with good antithrombotic effects [1,2,3]
It was found that the solubility of heparin in DCM could not be improved by simple physical mixing with phospholipids
differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR), Nuclear Magnetic Resonance (NMR), and Scanning electron microscopy (SEM) analyses confirmed the successful preparation of the HEP–Pc complex

Summary

Introduction

Unfractionated heparin (UFH) is a natural and widely used anticoagulant drug with good antithrombotic effects [1,2,3]. Its main route of administration is intravenous injection or subcutaneous injection, which limits the long-term use of heparin. Effective oral heparin preparations can greatly increase patient compliance. Due to the high molecular weight, high negative charge, and susceptible enzymatic degradation of heparin, direct oral administration of heparin is ineffective. In order to overcome the poor bioavailability of oral heparin, several research groups have tried various drug delivery systems, such as liposomes, complexes of heparin and hydrophobic organic bases, enteric coatings, and aerosols [4,5,6]. No oral heparin preparation has entered the market at present

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Discussion

Conclusion