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Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery

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Low molecular weight heparin loaded pH-sensitive microparticles.

Yvette Meissner¹, Nathalie Ubrich¹, Fatima El Ghazouani¹

¹InsermU734-EA3452, Faculty of Pharmacy, Nancy, France.

International Journal of Pharmaceutics

|December 8, 2006

Summary

Oral colonic-targeted microspheres were developed for low molecular weight heparin (LMWH) delivery to treat inflammatory bowel disease. This approach aims to improve efficacy and reduce bleeding risks associated with parenteral LMWH administration.

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Area of Science:

Pharmaceutical Technology
Drug Delivery Systems
Biomaterials Science

Background:

Parenteral low molecular weight heparin (LMWH) is effective for inflammatory bowel disease but carries risks of severe hemorrhage.
There is a significant need for oral, colonic-targeted LMWH formulations to improve safety and localized delivery.

Purpose of the Study:

To develop and characterize pH-sensitive microspheres for the oral colonic delivery of enoxaparin, a type of LMWH.
To optimize microsphere preparation for efficient drug entrapment and controlled release in the colon.

Main Methods:

Enoxaparin was encapsulated into Eudragit P4135F microspheres using a double emulsion technique (solvent extraction/evaporation).
Preparation parameters including polymer concentration, inner phase volume, and surfactants (Sorbitan monostearate, hexadecyltrimethylammonium bromide) were optimized.
In vitro drug release studies were conducted at different pH values (pH<6 and pH 7.4).

Main Results:

Solvent evaporation yielded higher enoxaparin entrapment rates (70.1%) compared to solvent extraction (46.5%).
Sorbitan monostearate improved encapsulation efficiency and resulted in smaller particle sizes (120-160 µm).
Microspheres demonstrated pH-dependent drug release, retaining LMWH at pH<6 and releasing it rapidly at pH 7.4.

Conclusions:

Optimized pH-sensitive microspheres efficiently encapsulate LMWH and provide pH-controlled release, suitable for colonic delivery.
These microspheres offer a promising platform for the oral administration of heparin in inflammatory bowel disease therapy, potentially reducing hemorrhagic risks.