Study On The Preparation Of Curcumin-loaded PLGA Nanoparticles In Microchannels And Its Pharmacokinetics

Curcumin,a natural diphenolic compound extracted from turmeric Curcuma longa,is a well application perspective drug,due to it has a lot of pharmacological activities such as anti-inflammatory,antibacterial,anticancer and so on,and is especially with little toxic effects in cancer prevention and treatment.However,the clinical application of curcumin is seriously limited by its poor stability,poor water solubility,short half-life and low bioavailability.Thus,it is significant to develop a new formulation for improving the water solubility and bioavailability of curcumin in clinical application.In this study,curcumin-loaded PLGA nanoparticles were successfully prepared by the method of interfacial precipitation in micro-channel.Curcumin was encapsulated in biodegradable poly(D,L-lactide-co-glycolide)solid lipid nanoparticles.The main contents and results are as follows:1)A precise and convenient HPLC method was established to determine the concentration of curcumin.The characteristic of linearity,recovery and precision were investigated with this method.2)Compared with several methods including solvent dispersing method,emulsion-solvent evaporation method,precipitation and rectangular microchannels method for preparing Curcumin-loaded PLGA nanoparticles(Cur-NPs).The influence of aqueous phase flow and concentration of aqueous phase,lipid phase flow and concentration of lipid phase flow,gas phase flow were investigated by single factor experiment of microchannels.3)The preparation process was optimized using response surface method.The Cur-NPs prepared with optimized preparation was characterized of its surface morphology,particle size,the Zeta potential,XRD and IR.4)Preliminary study on the phamacokinetics of its release in vitro,cellular entry,tissue distribution and so on.The results showed:the preparation optimized by single factors and response surface method in rectangular microchannels was a feasible novel method,and ideal Cur-NPs was obtained.The encapsulation efficiency was(94.92 ± 0.28)%,the average size was(107.5 ± 1.18)nm and the Zeta potential was-25.30 mV.The shape of Cur-NPs were good dispersion,smooth surface and spherical observed by TEM.The XRD and IR were showed that the curcumin was encapsulated in PLGA.Furthermore,experiment by dialysis method in vitro exhibited that the Cur-NPs had a good sustained release efficacy.Fluorescent microscope studies demonstrated that the cellular entry of Cur-NPs were much better than free Cur.Meanwhile,the pharmacokinetics study was showed that it could prolong the retention time in wistar rats,and be targeted to the liver.