| PurposeIn this study,mPEG-PLGA nanoparticles which contained simultaneously two Chinese medicines that is HT and SYR were prepared to achieve long-term and targeted nano-formulation.To explore the feasibility of constructing and investigate the discipline of mPEG-PLGA block copolymer as a carrier which contained Chinese multi-component nano-drug delivery systems.To provide a scientific basis for the treatment of hepatitis B ills of this innovative drug research,but also provide a reference for the other poor stability and short half-life soluble drugs.Method and result1.The process inspection and lyophilized research of SH-NPsCombining single factor method and central composite design to study the optimization of process and prescription with size,encapsulation efficiency and drug loading as index.The particles were prepared by precipitation method with stabilizing agent Poloxamerl88.The particles showed average diameter of(71.03±2.89)nm,zeta potential of(-25.02±0.99)mV,drug-loading coefficient of(32.38± 1.21)%,encapsulation ratio of(12.01±0.32)%and PDI of(0.19±0.008).The comparative experimental method on freeze-dried process clarified that the freeze-dried powder with 5%mannitol was white and fluffy,and presented well re-dissolved.The encapsulation efficiency,zeta potential and PDI of the lyophilized particles did not changed significantly,but the size with a little addition.2.Research on characteristics of SH dual drug loaded nanoparticleThe morphology of freeze-dried SH dual drug loaded nanoparticles was observed by transmission electron microscope;Zetasizer Nano-ZS90 laser particle size analyzer determined the Zeta potential,particle size and PDI.The DSC curve showed that loaded drugs were amorphous without being affected by types of drugs.The release results of both model drugs clarified that the release curve was in line with Higuchi equation with the pH7.4 of release medium,37? of release temperature,and 100r·min-1 of stirring speed.To some extent,both model drugs possessed controlled release.SH-NPs within 144h release nearly is saturated and the cumulative release percentage is close to 85%.3.The pharmacokinetics and tissue distribution in vivoresearch of SH-NPsSaline solution looked upon as control group,after injection into rats tail vein,UPLC analyzed the concentration of SYR and HT.Pharmacokinetics data was dealed with by DAS2.0.The process of time-drug result of controlled and particles groups confirmed to two compartment model.At the same administration dose,T1/2? of SYR and HT in the particles group were 3.7 and 5.5 times than that in the controlled group.The T1/2? and the AUC increased significantly showed that particles could extend drug circulation time in the body,and improve the bioavailability of both model drugs,with some long-cycle effects contrast to native drug solution.After injecting SH-NPs and SH saline solution into rat tail vein,UPLC analyzed the plasma concentration and some tissues of SYR and HT to calculate accumulation situation by trapezoidal method.The result showed that particles group could improve SYR and HT content in the liver compared to controlled group(P<0.05).With the standard of the relative uptake rate and relative target rate,particles group could improve the distribution of SYR and HT in the liver,which means nanoparticles possessed targeting.ConclusionSH-NPs was successfully prepared.The appearance of nanoparticles was spherical,the size of nanoparticles was under 100 nm,and the PDI was narrow.The release data was in line with Higuchi equation.Theclearance of nanoparticles in the mice was slower which signified that particles extended the circle time of drugs in the rats.And tissue distribution showed that the particles possessed livertargeting. |
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