Study On The Preparation And In Vivo Pharmacokinetics Of CS-CT/PR-Dual-Loaded PLGA Nanoparticles

OBJECTIVE To prepare Calcitonin/Puterrin-PLGA-Dual-Loaded nanoparticles modified by Chitosan,and investigate their in release behavior and in vivo pharmacokinetics.METHODS CS-CT/PR-NPs were prepared by the double emulsion solvent evaporation technique with PLGA as a carrier material;the formulation of CS-CT/PR-NPs was optimized by orthogonal design;the morphology of CS-CT/PR-NPs was observed by transmission electron microscope;the mean particle size,particle size distribution and Zeta potential were measured by laser particle size analyzer;the entrapment efficiency and drug loading were measured by ultracentrifugation;the in vitro release behavior was studied by dialysis;in vivo pharmacokinetics of CS-CT/PR-NPs were studied in comparison with CT,CS-CT-NPs.RESULTS CS-CT/PR-NPs were spherical in shape with the mean particle size of(190±2.65)nm,particle size distribution of(0.117±0.027)and Zeta potential of(16.5± 1.08)mV.The entrapment efficiency was(75.7±1.15)%,and the drug loading of CT was(3.47±0.31)%,while those of PR were(50.9±1.08)%and(4.68±0.19)%,respectively.The profiles of in vitro release had the features of sustained-release.The T1/2 were(186.86±0.73)、(283.67±4.12)、(333.29±5.64),AUC0-t were(81724.45± 185.78)、(126888.88±335.38)、(207747.75±237.24),MRT were(287.49± 1.63)、(464.17±6.98)、(523.81±9.67),Vz/F were(0.0119±0.00004)、(0.2513±0.00113)、(0.1700±0.00108).CONCLUSION CS-CT/PR-NPs were prepared successfully and showed a sustained-release characteristic with high entrapment efficiency,which may improve the oral bioavailability of CT and provide the experimental reference for preparing the dual-loaded nanoparticles.And the AUC and absolute bioavailability were markedly improved afer oral.