Preparation And Quality Evaluation Of CHHPS Nanoparticles

Turmeric pigment is a natural polyphenolic turmeric obtained from rhizomes,which is mainly found in ginger,birch plants.Curcumin?CUR?is the most important active ingredient in turmeric pigment,which accounts for about 75 %.CUR has a wide range of pharmacological effects,with anti-inflammatory,anti-oxidation,anti-tumor and other biological activity.Its broad spectrum of anti-cancer,a variety of cancer with cytotoxic effects,such as gastric cancer,osteosarcoma,lung adenocarcinoma and so on.CUR can interact with different molecular targets to participate inflammation,has anti inflammatory effects,and has good application prospects for cardiovascular disease such as hyperlipidemia and atherosclerosis,Have good clinical application value and research and development potential.However,CUR not only has poor solubility,but also has low bioavailability,which greatly limits the wide application of CUR in clinic.Domestic and foreign research reports show that through the transformation and modification of the drug structure,the bioavailability of the drug can be improved and enhance the role of drugs on tumor cell targeting inhibition.It was found that the CUR derivatives derived from Triphenylphosphine?TPP?could enhance the tumor cell targeting inhibition by electronically displacing lipophilic cations to selectively accumulate in the mitochondria of tumor cells.The main work of this paper involves the following parts:The CUR chlorinated derivatives?CURCD?were synthesized by the etherification of halogenated alkanes with CUR as raw material,And the Curcumin triphenylphosphine derivative?CURTP?was synthesized by addition reaction of CURCD with TPP.The effects of molar ratio,reaction time,temperature and recrystallization solvent on the yield of the product were investigated.The results showed that CURTP was successfully synthesized and identified by MS and ¹HNMR.The equilibrium solubility of CURTP in water was 53.31 ?g/mL.The oil and water partition coefficient was 0.61.Compared with CUR,CURTP solubility is highly improved.The CURTP melting point was measured at 128.50 130.50 °C.The HA-g-mPEG was synthesized by grafting hyaluronic acid through N-boc-glycine to polyethylene glycol as the drug carrier for preparing CURTP nanoparticles.And the synthesis of HA-g-mPEG was identified by IR.The CHHPS were prepared by HA-g-mPEG as the carrier.The average entrapment efficiency was 81.60 %,the average particle size was 200.00 nm,and the Zeta potential was-31.30 mV.The results showed that the pharmacokinetic properties of CHHPS changed significantly compared with CUR and CURTP.The pharmacokinetic properties of CHHPS were significantly higher than that of CUR and CURTP.The AUC?0-72h?of CURTP and CHHPS were 721.30 ?g /L·h and 2217.33 ?g /L·h,respectively,which was nearly 3 times of that of the former;the MRT_0-72hof CURTP was 0.54 h,and CHHPS was 2.94 h,CHHPS had a longer average residence time and longer duration in vivo.The Cl of CURTP and CHHPS were 10949.50 L/h/kg and 3583.42 L/h/kg,respectively.The total clearance of CHHPS was significantly lower than that of CURTP,indicating that CHHPS was slow to be eliminated and has a longer duration of action in vivo.