The characteristics, biodistribution and bioavailability of a chitosan-based nanoparticulate system for the oral delivery of heparin

Heparin is a potent anticoagulant; however, it is poorly absorbed in the gastrointestinal tract. In this study, we developed a nanoparticle (NP) system shelled with chitosan (CS) for oral delivery of heparin; the NPs were prepared by a simple ionic gelation method without chemically modifying heparin. The drug loading efficiency of NPs was nearly 100% because a significantly excess amount of CS was used for the CS/heparin complex preparation. The internal structure of the prepared NPs was examined by small angle X-ray scattering (SAXS). The obtained SAXS profiles suggest that the NPs are associated with a two-phase system and consist of the CS/heparin complex microdomains surrounded by the CS matrix. The stability of NPs in response to pH had a significant effect on their release of heparin. No significant anticoagulant activity was detected after oral administration of the free form heparin solution in a rat model, while administration of NPs orally was effective in the delivery of heparin into the blood stream; the absolute bioavailability was found to be 20.5%. The biodistribution of the drug carrier, 99(m)Tc-labeled CS, in rats was studied by the single-photon emission computed tomography after oral administration of the radio-labeled NPs. No significant radioactivity was found in the internal organs, indicating a minimal absorption of CS into the systemic circulation. These results suggest that the NPs developed in the study can be employed as a potential carrier for oral delivery of heparin. (C) 2009 Elsevier Ltd. All rights reserved.