A Cost-Effective Nano-Sized Drug Delivery System With High Drug Loading Capacity For Controlled Release Prepared Via Flash Nanoprecipitation

As one of the important nano-sized drug delivery systems,drug-loaded nanoparticles(NPs)have been widely applied in the medical fields including biomedicine and nano-pesticide due to their targeted administration and rich multi-functional transformation potential.Flash Nanoprecipitation(FNP)is a novel technique,possessing the abilities of the rapid construction of drug-loaded NPs and good reproducibility of experimental results.However,the high cost of commonly used block copolymers is not conducive to the further popularization and application of this technique.Moreover,it is difficult to prepare NPs with good storage stability for weakly hydrophobic molecules or drugs via FNP technique.Finally,the preparation of functional nanoparticles often requires complex chemical modification of polymers or drug molecules,which deviates from the concept of green chemistry.To address the above contradiction,this article uses low-cost polyvinylpyrrolidone(PVP)as a stabilizer and chitosan(CS)as a drug trapping agent and pH responsive agent on the basis of FNP technique,aiming to obtain pH-responsive NPs via a cost-effective method.The size,dispersion and drug-carrying capacity of NPs can be systematically tuned by adjusting the Reynolds number,the concentration of CS and PVP.Meanwhile,the universality of this method to different kinds of drugs and the in vitro release behavior of drug-loaded NPs were studied.The research contents of this paper include the following aspects:(1)In this paper,the weakly hydrophobic drug curcumin(CUR)was used as a model drug,and pH-responsive CUR-loaded were successfully prepared via FNP technique.It has found that the amphiphilic homopolymer PVP has a good stabilizing effect on hydrophobic drugs.CS-containing NPs have better dispersibility(PDI<0.1),extremely high encapsulation efficiency(95.2%)and satisfactory storage stability(storage time>60 days under sealed conditions at room temperature).(2)Using lutein(LTE)and itraconazole(ITZ)as model drugs,we further studied the universality of”PVP+chitosan combination" in FNP technique,and found that this method has an obvious optimization effects on the particle size,dispersibility,drug-loading capacity and particle structure of drug-loaded NPs.(3)The drug release behavior of nanoparticles was studied by UV-Vis absorption spectroscopy,and it was found that the CS-containing NPs have better protection for drugs under neutral conditions and can greatly improve the cumulative released quantity of drugs under acidic conditions.