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  • Title: Preparation, optimization, and in-vitro/in-vivo/ex-vivo characterization of chitosan-heparin nanoparticles: drug-induced gelation.
    Author: Shahbazi MA, Hamidi M, Mohammadi-Samani S.
    Journal: J Pharm Pharmacol; 2013 Aug; 65(8):1118-33. PubMed ID: 23837580.
    Abstract:
    OBJECTIVES: Management of blood coagulation-related diseases is currently limited by the inability to provide an adequate drug concentration in blood circulation for a long term. As a promising way to overcome this problem, the long-acting forms of these drugs have attracted many interests in recent years. METHODS: In this study, chitosan-heparin nanoparticles were prepared as a polymeric delivery system intended for the prolonged intravenous delivery of heparin where the drug was used as both the therapeutic agent and a gel-forming counter-ion. The nanoparticle preparation method was optimized using a Taguchi orthogonal array. Critical formulation variables were optimized in this study in terms of their corresponding effects on the target response of particle size. Nanoparticles were characterized by the Fourier transform infrared spectroscopy, transmission electron microscopy and zeta potential. KEY FINDINGS: The size, polydispersity index, zeta potential and encapsulation efficiency for the optimized formulation were found to be 61.33 ± 1.53 nm, 0.06, +15.7 mv and 74.16 ± 1.27%, respectively. The sizes of the prepared drug-loaded nanoparticles were stable at least 1 week at room temperature and 3 months in refrigerator. CONCLUSIONS: The ex-vivo and in-vivo tests on the heparin-chitosan nanoparticles using activated partial thromboplastin time (aPTT) as the biological index were indicative of a smoother and longer elevation in aPTT in the presence of nanoparticulate drug.
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