title: The characteristics, biodistribution and bioavailability of a chitosan-based nanoparticulate system for the oral delivery of heparin.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, National Cheng Kung University, Tainan City, Taiwan, ROC.
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Chen
authors.forename: Hen-Sheng
authors.initials: HS
authors.lastname: Wong
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.forename: Hsin-Lung
authors.initials: HL
authors.lastname: Chen
authors.forename: Shiaw-Pyng
authors.initials: SP
authors.lastname: Wey
authors.forename: Kiran
authors.initials: K
authors.lastname: Sonaje
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Lin
authors.forename: Che-Yi
authors.initials: CY
authors.lastname: Chu
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D006493:Heparin / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012542:Scattering, Radiation
chemical_list: D000925:Anticoagulants; D004337:Drug Carriers; D006493:Heparin; D048271:Chitosan