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, (99m)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.

Rapidly self-expandable polymeric stents with a shape-memory property.

A novel biodegradable stent, made of chitosan films cross-linked with an epoxy compound, with a shape-memory property was developed. To reduce their crystallinity, glycerol and poly(ethylene oxide) were blended in the chitosan films. The mechanical properties of the prepared stent were studied using a commercially available metallic stent as a control. After blending, the ductility of the chitosan films was improved, and the compressive strength of the stent was significantly enhanced. The metallic stent could tolerate elastic deformations of 10% before becoming irreversibly deformed, while the polymeric stent was able to withstand deformations up to 30% and still regain its original configuration. The developed stent could rapidly expand ( approximately 150 s) from its crimped (temporary) to fully expanded (permanent) states stimulated by hydration, which is advantageous considering avoiding its migration during in vivo deployment. In the preliminary animal study, the implanted stent was found to be intact, and no thrombus formation was seen in the stent-implanted vessel. This degradable stent can be an attractive alternative to metallic stents and may serve as a useful vehicle for local drug delivery.