Preparation Of 5-Fluorouracil-Loaded Sodium Alginate Nanoparticles

Nanoparticles was thought to have the broad application prospect as a novel drug carrier.But nanoparticle carrieried often face problems of preparation process and biological safety.To successfully prepare drug delivery system,nanoparticles with simple and effective method avoiding use of potentially toxic solvent and components,5-fluorouracil(5-Fu)was chosen as a model chemotherapeutic drug and emulsified.5-Fu-loaded nanoparticles were prepared with the sodium alginate.To determine the prescription of sodium alginate of 5-fluorouracil-loadede nanoparticles,we use the encapsulation efficiency as the main evalution index in the previous study,accroading to single factor studies,the most influential factor to encapsulation efficiency were the concertration of 5-Fu,sodium alginate,CaCl2,lecithin and stirring speed,and then through the orthogonal expetiment to optimize the prescription,and ultimately determine the prescription of sodium alginate of 5-Fu-loaded nanoparticles are the concertration of 5-Fu is 4 mg/mL,the theconcertration of sodium alginate is 0.7mg/mL,the concertration of CaCl2 is 10mL,stirring speed is 1200rpm.In this study,we improved the analysis method of 5-Fu,we used high performance liquid chromatography method to improve detection accuracy,and research the precision,stability and recovery of this method.In order to evaluate the quality of the optimum formula of 5-Fu-loaded nanoparticles,we detected encapsulation efficiency and the drug loading capacity,self-emulsifying rate,shape of nanoparticles,size and distribution of nanoparticles and the release rate in vitro.The results indicate that RSD of the presion of high,medium and low concentrations are 0.75%,0.53%and 0.75%,RSD of stability is 0.68%,RSD of recovery was 1.27%,which indicate that this method was simple,fast,accurate and can do quantitive analysis of 5-Fu·The sodium alginate of 5-Fu-loaded nanoparticles prepared by the best prescription with the encapsulation efficiency of 56.2914.35%,the drug loading capacity of 8.69±2.66%..The freeze dried nanoparticles can completely emulsified within 15 min,the shape of nanoparticles is spherical or oval,uniform distribution,size of nanoparticles was about 300nm,the cumulated release is about 90%in 2 days.In the freeze-dried products,which have commonly lyoprotectant mannitol,glucose,sucrose and so on.From the results of the protective agent of formulation lyophilized found that the formulation was not added cryoprotectant freeze dried lyophilized sample of the projection can not formed,and poor dispersion,higher concentrations of cryoprotectant,the appearance becomes lyophilized sample neat enough,it may be due to high concentrations of cryoprotectant in a freeze dried resulting in a change in the environment.Among mannitol as a protective agent concentration at 2%,the appearance of other indicators lyophilized product than meet the requirements.5-Fu was mainly used for the treatment of gastrointestinal malignancies,so we choice gastric cancer cell line SGC-7901 as the research object,MTT assay was used to investigate the inhibition effect of sodium alginate of 5-Fu-loaded nanoparticles to cells.The results showed that inhibition effect of sodium alginate of 5-Fu-loaded nanoparticles was showed time-dependent and concentration-dependents,winthin 48 hours the higher concentration of nanoparticles,the longer time of action,inhibition of cells is stronger.This study suggested that the nanoparticles will be used as a potential carrier of chemotherapeutic drugs.