Delivery of LMW heparin via surface coated chitosan/peg-alginate microspheres prevents thrombosis

Thomas Chandy, Gundu H.R. Rao, Robert F. Wilson, Gladwin S. Das

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Heparin remains the gold-standard inhibitor of the process involved in the vascular response to injury. Continued anticoagulation is achieved by subcutaneous administration of low-molecular-weight heparin (LMW Hep) or with an orally active anticoagulant such as warfarin. An oral heparin would avoid the inconvenience of subcutaneous injections and adverse events associated with warfarin. A mild chitosan/PEG/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as heparin and LMW Hep was investigated. Heparin and LMW Hep entrapped alginate beads were further surface/enteric coated with chitosan and cellulose acetate phthalate (CAP) via carbodiimide (EDC) functionalities. It was observed that approximately 70% of the content is being released into Tris-HCI buffer, pH 7.4 within the initial 6 hours and no significant release of LMW Hep was observed from enteric coated microspheres (12%) during treatment with 0.1 M HCI, pH 1.0 for 4 hours. But acid treated capsules had released almost all the entrapped LMW Hep into Tris-HCI, pH 7.4 media within 6 hours. From scanning electron microscopic and swelling studies, it appeared that the surface coatings (via chitosan and CAP) had modified the alginate microspheres and subsequently the drug release. The released heparin and LMW Hep had shown their anticoagulant functions. These results established the feasibility of modifying the formulation in order to obtain the desired controlled release of bioactive agent (LMW Hep), for a convenient pH dependent delivery system.

Original languageEnglish (US)
Pages (from-to)87-96
Number of pages10
JournalDrug Delivery: Journal of Delivery and Targeting of Therapeutic Agents
Issue number2
StatePublished - 2002

Bibliographical note

Copyright 2008 Elsevier B.V., All rights reserved.


  • Alginate
  • Cellulose Acetate Phthalate
  • Chitosan
  • LMW Heparin
  • Microencapsulation
  • Polyethylene Glycol


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