Study On The Preparation Of Starch Nanoparticles And Its Drug-Loaded Performance Using High-Speed Shear Mixing Technique

Starch nanoparticles(SNPs)are active carriers with a large specific surface area,good biocompatibility and degradability.The former usually uses a large amount of emulsifier,a high oil/water ratio and a low concentration of starch solution,resulting in low yields,while the latter is a new method for the synthesis of nanoparticles with the aid of high energy technology with low emulsifier usage and high production efficiency.The high speed shear technique has the advantages of simple equipment,low cost and ease of handling,and is a common means of mixing for the preparation of fine emulsions.High-speed shear mixing was used to prepare loaded losartan SNPs with using losartan as the model drug.The effects of starch type,starch solution concentration,cross-linking agent type and addition amount,cross-linking time and high-speed shear rate on the characteristics,drug loading and slow release performance of SNPs were systematically investigated,and the preparation effects of high-speed shear and traditional mechanical mixing process were compared.The main conclusions are as follows:The SNPs produced by high speed shear mixing with sodium tris/hexametaphosphate as the cross-linking agent were round,full and spherical in shape,but the uniformity of the particles was not good;the straight straigh/branched chain ratio of corn starch>1 was beneficial to the production of cross-linked SNPs,but the particles were sunken,heavily adhered and had low yields;soluble starch was more suitable as a raw material than corn starch to obtain well rounded,well dispersed and high yielding SNPs.The optimum conditions for the preparation of SNPs were as follow:15%concentration of soluble starch solution,25%addition of sodium trimetaphosphate,3 h crosslinking time,5000 r/min shear rate,smallest particle size(655.2 nm)and highest yield(69.5%);25%concentration of starch solution,30%addition of sodium hexametaphosphate,3 h crosslinking time,6500r/min shear rate,smallest particle size(805.2 nm)and highest yield.FTIR,XRD and DSC showed that the soluble starch was successfully cross-linked with the cross-linker and the SNPs were present in an amorphous structure with good thermal stability.Compared with the conventional mechanical stirring process,the high-speed shearing technique was not only more energy efficient(24.32×10~9kJ/(m~3kg)),but also produced SNPs with smaller particle sizes and higher yields and encapsulation rates.The SNPs made from corn starch with a straight chain/branched chain ratio>1 showed low encapsulation of losartan drug,while the best encapsulation performance was obtained from soluble starch;under optimal conditions,the encapsulation rates of losartan drug by SNPs prepared by high-speed shear mixing were 30.7%and 36.5%,and the drug loading capacity was 2.6%and 3.5%,respectively,when sodium tri/hexametaphosphate was used as the crosslinker.The structural characterization by FTIR,XRD and DSC showed that the losartan was successfully loaded into the SNPSs and there was no chemical reaction between the drug and the soluble starch,and the SNPs existed in an amorphous structure with good thermal stability.In vitro release study showed that the release rate of losartan starch nanoparticles was the fastest in the simulated large intestine(pH=9.0),followed by the small intestine(pH=7.2),and the slowest in gastric juice(pH=1.2).The above results showed that the starch nanoparticles with small particle size,round shape,high yield and losartan loading could be prepared by high speed shear mixing,but its particle homogeneity is not good.