Control Of Inner Structure Of NPs And Their Release Behavior Based On Flash Nanoprecipitation

Flash Nanoprecipitation(FNP)is a new technology that has emerged in recent years to prepare nanoparticles(NPs)by chemical engineering methods.Compared with the traditional method of preparing NPs by thermodynamic self-assembly,the advantage of FNP is that it is based on the kinetics control,which significantly improves the drug loading of NPs and reduces the preparation time of NPs to microseconds.The FNP method is based on very rapid precipitation.The coated hydrophobic molecules rapidly precipitate in water and form nucleus,which is then encapsulated and protected by a stabilizer to form stable water-dispersed NPs.The more hydrophobic the hydrophobic molecule,the worse the solubility in water,the faster the nucleation of the hydrophobic molecule,and the easier it is to form a close hydrophobic core,which helps to prepare stable NPs.However,after the stable drug-loaded NPs prepared by the FNP method are formed,their strong stability leads to the drug's release behavior is not easily controlled,and the drug is not easy to be completely released;On the other hand,it is not easy to use FNP method to produce stable NPs for weakly hydrophobic molecules or drugs with limited precipitation ability for nucleation.These limit the further widespread use of FNP in the NP field.In this paper,we use the weak hydrophobic antitumor drug sorafenib(Log P=5.1)as a drug and a biocompatible amphiphilic block copolymer poly(ethylene glycol)-block-poly(lactic acid)(PEG-b-PLA)as a stabilizer,successfully prepared sorafenib NPs?extending the application of FNP method in low hydrophobicity drugs.At the same time,it was found that the internal structure of NPs can be systematically controlled by adjusting chemical factors such as the ratio of drug-stabilizers,fluid flow rate,and Reynolds number in the preparation process,and the release behavior of NPs can be further regulated,and at the same time,the release mechanisms of drug-loaded NPs with different internal structures were studied.The specific research work is described as follows:Firstly,stable sorafenib NPs were prepared by FNP.Compared with the conventional self-assembly method,Sorafenib NPs were prepared and compared.It was found that sorafenib NPs prepared by FNP method are smaller in size and higher in drug loading.,and can be stable for more than a week.Secondly,the influence of the mass ratio of drug-stabilizer and the fluid velocity(Reynolds number)on the size structure of NPs was studied by dynamic static static light scattering instrument.It was found that the size and internal structure of NPs can be effectively controlled.With the gradual increase of the mass ratio of drug-stabilizer or Reynolds number,the size of NPs increases,and at the same time,the internal structure of NPs gradually changes from a compact structure to a loose structure.Finally,the drug release behaviors and release rates of NPs with different internal structures were studied by means of static and dynamic light scattering and UV-visible absorption spectra.The drug release rate of NPs with a tight internal structure was found to be relatively slow,whereas the drug release rate of NPs with a loose internal structure was relatively fast.