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The preliminary evaluation on cholesterol-modified pullulan as a drug nanocarrier;Abstract
To further develop cholesterol-modified pullulan self-aggregated nanoparticles (CHSPNs) as a drug nanocarrier, CHSP was synthesized and characterized. Its cholesterol degree determined by 1H 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 200mg/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 (t1/2) 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.;Keywords
Cholesterol-modified pullulan
epirubicin
nanoparticles
pharmacokinetics
stability
toxicity;Introduction
Nanomaterials are structures with at least one dimension of 100nm or less. These materials have specific physic-chemical properties different to bulk materials of the same composition, and are increasingly being used for commercial purposes such as fillers, catalysts, semiconductors, cosmetics, microelectronics and drug carriers (Landsiedel et al., 2010). Using the nanoparticles (NPs) to deliver drugs, the absorption of poorly water-soluble pharmaceuticals may be improved and led to pro
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