Research On Antheraea Pernyi Silk Fibroin Nanoparticles Loaded Drugs

Silk fibroin of domestic silkworm Bombyx mori（B.mori SF）is widely used in various fields,for example wound dressings,surgical sutures,drug delivery enzyme,immobilization materials and tissue engineering because of its excellent biodegradability,biocompatibility and breathable oxygen permeability.At present,silk fibroin as slow releasing substrate loaded drugs is mainly focused on silk fibroin hydrogel,silk fibroin membrane and silk fibroin microspheres.In addition to these advantages of silk fibroin,the Antheraea pernyi（A.pernyi）silk fibroin（ASF）contains the tripeptide sequence Arg-Gly-Asp（RGD）structure which makes it as a wound auxiliary,surgical suture,tissue engineering scaffold materials and drug release material well.In this paper,Ca²⁺in calcium gluconate was used to prepare ASF nanospheres.And this study is on the release of ASF nanospheres loaded different molecular drugs.The study found that the nanoparticles size is uniform from 200nm to 500nm,whether it contained macromolecular insulin or small molecular 5-fluorouracil.The average diameter of ASF nanospheres is about 300nm.The dispersion coefficient is high and uniformity is good.The utilization rate of silk fibroin and the coverage rate or the drug loading rate of insulin changed with the weight of drug quality.With the increase of the amount of drug input,the utilization rate of silk fibroin gradually decreased.But the utilization rate of silk fibroin was high and remained about 90%.The coverage rate of insulin decreased while the insulin loading rate showed an increasing trend with the increasing of insulin.It is the best point at M_（INS）/M_（ASF）=12/100 where the coating rate of insulin was 27.20%and drug loading rate of insulin was 3.62%through the analysis of the coating rate and the loading rate of insulin.The small molecule 5-fluorouracil loading rate is related to the amount of 5-fluorouracil.The drug loading rate is positively correlated with the amount of drug.However,the rate of coating is not correlated with the amount of drug delivery.When the mass ratio of small molecule 5-fluorouracil with ASF reached 12:100(M_（5FU）/M_（ASF）=12/100),the optimal ratio was reached.The drug loading rate reached 3.76%and the coating rate was 30.2%.ASF nanospheres have different particle sizes in different pH environment owing to different swelling.Under the neutral conditions（pH=7.4）,the swelling of the particles is most obvious resulting in having a higher drug release whether it loaded macromolecular insulin or small molecules 5-fluorouracil.But in acidic conditions（pH=5.2）,ASF nanospheres are almost no swelling so that the amount of macromolecular insulin release is very low.So that ASF nanospheres have pH-sensitive characteristics.After 5 days of release in the neutral conditions,the drug release rate of the insulin-loaded ASF nanospheres（ASF-INS nanospheres）was over 50%.The rate of release increased by the straight line and increased slowly after 5 days.Then the release rate was getting steady.The release of the small molecule 5-fluorouracil loaded ASF nanospheres（ASF-5FU nanospheres）did not pH-sensitive characteristics,although ASF nanospheres had different swelling conditions in different pH conditions.Since 5-fluorouracil is a small molecule drug,the effect of its swelling on the release is not significant.After a 3-day release,it was found that almost 70%of the 5-fluorouracil remained in the ASF-5FU nanospheres.After compatibility testing（XRD,IR）and thermal stability testing（DTG）,it was found that the drug-loaded ASF nanospheres formed by self-assembly can be a good combination,whether it loaded macromolecule insulin or small molecule 5-fluorouracil.And the results showed that ASF silk nanospheres are suitable as carrier for the drug release.