The Study Of The Effect Of Molecular Structure Of Chitosan On Character Of Norcantharidin Chitosan Nanoparticles In Vitro And In Vivo

Objectives: To study the effect of different deacetylation degree (DD) and molecular weight (MW) of chitosan (CS) on the properties of norcanthardin loaded chitosan nanoparticles (NCD-NP) in vitro in order to optimize the prescription and formulation of NCD-NP. To study the liver targeting trend of all kinds of norcantharidin chitosan nanoparticles(NCD-NP) in mice in order to discuss the influence of targeting of different parameters of CS.Methods: Norcanthardin (NCD) was used as model drug and the CS-NP was prepared by ionic crosslink process using different kinds of chitosan with various DD and MW. The properties of those CS-NPs, such as the appearance, mean size, zeta potential, encapsulation efficiency (EE), loading capacity (LC) and the drug release rate in vitro, were detected. The concentrations at definite schedule of NCD in mice plasma and liver were determined respectively by HPLC after tail intravenous injection administration of narcanthardin solution (NCD-SOL) or all kinds of NCD-NPs. The targeting ability to liver was evaluated by r_e which equal to (AUC)_NCD-NP/ (AUC)_NCD-SOL.Results All kinds off CS-NPs were spherical with narrow size distribution. With the decrease of DD of CS, the mean size of the CS-NP was increased while the zeta potential, the EE and LC of NCD were all decreased. With the decrease of MW of CS, the mean size of the CS-NP was diminutive correspondingly while the zeta potential, the EE and LC were not changed significantly. Both the decrease of DD and MW of CS could render the speed-up of the release rate of NCD from the CS-NP in vitro. The examinations reveal that the NCD-NP with bigger bulk has liver targeting, while the NCD-NP with very small bulk has not targeting ability.Conclusions Both the DD and MW of CS had significan effect on the properties of the CS-NP in vitro. Through the adjustment on the two molecular parameters, CS-NP with various mean size and drug release rate could be obtained. The NCD-NP with big bulk has liver targeting and it can improve curative effect and reduce toxicity of NCD. The liver targeting ability of NCD-NP was achieved by the interception of reticoendothelial system (RES)...