Journal
DRUG DELIVERY
Volume 21, Issue 7, Pages 501-508Publisher
INFORMA HEALTHCARE
DOI: 10.3109/10717544.2014.895068
Keywords
Cholesterol-modified pullulan; epirubicin; nanoparticles; pharmacokinetics; stability; toxicity
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Funding
- Natural Science Foundation of Hebei Province [H2012201069, B2013201181]
- Science and Technology Planning Project of Hebei Province [13272705]
- Natural Science Foundation of Hebei University, China [2010-193]
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To further develop cholesterol-modified pullulan self-aggregated nanoparticles (CHSPNs) as a drug nanocarrier, CHSP was synthesized and characterized. Its cholesterol degree determined by H-1 NMR was 5.2 cholesterol groups per hundred glucose units. CHSPNs were prepared in aqueous media and characterized by dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM). These nanoparticles were almost spherical in shape, and the zeta potentials of CHSPNs were near zero in aqueous media. CHSPNs can be stable at least 2 months with no significant size and zeta potential changes. Single dose toxicity test in mice was investigated for the safety evaluation of CHSPNs as a drug nanocarrier, and the result showed CHSPNs were well tolerated at the dose of 200 mg/kg in mice. Epirubicin (EPI)-loaded CHSPNs (EPI-CHSPNs) were prepared and the in vivo pharmacokinetics and biodistribution were studied. Compared with the EPI solution, EPI-CHSPNs have exhibited higher plasma drug concentration, longer half-life time (t(1/2)) and the larger area under-the-curve (AUC). Moreover, the drug level of EPI-CHSPNs increased in liver and decreased in heart. The results indicated that CHSPNs were stable, safe and may be a promising drug delivery carrier.
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