Preparation And Properties Of Sophorolipids-based Solid Dispersion And Nanoemulsion

Sophorolipids(SLs)is one of the highest yielding biosurfactants at present,with functions of emulsification,dispersion,solubilization,foaming,wetting,antibacterial,antitumor,etc.It is also non-toxic,biodegradable and non-degradable sensitive,bio-renewable,and environmentally compatible.SLs is a mixture of a series of structural analogues synthesized naturally by microorganisms,and is composed of two parts,one is a hydrophilic sophorose(two glucose molecules bonded by β-1,2 glycosidic bonds)and another one is hydrophobic saturated or unsaturated long chain ω-(or ω-1)hydroxy fatty,mainly divided into two types of acidic and lactonic.Dehydration condensation to form ester is called lactonic sophorolipids(LSL).No esterification reaction occurs,and the weakly acidic aqueous solution is called acidic sophorolipids(ASL).Generally speaking,LSL has higher lipophilicity,can reduce the surface tension of liquid,and has higher antibacterial and anti-cancer activities;ASL has better water solubility and foaming ability,and is an excellent foaming agent,available used as pharmaceutical excipients.SLs has high output and excellent performance,and is one of the hottest biological surfactants in research.It has been used in oil extraction,daily chemical,food,pesticide,pharmaceutical and other industries.The higher fermentation cost of SLs limits its large-scale production.The fermentation requires a combination of hydrophilic and hydrophob ic carbon sources,in which hydrophilic accounts for 10%-30% of the fermentation cost.Lignocellulose is the most abundant source of cellulose in the world.Wheat is one of the three major crops in the world and rich in lignocellulose.The cellulose and he micellulose can be hydrolyzed,but the rigid structure of lignin hinders its hydrolysis.It is necessary to find a suitable method for stripping lignin and investigate the ability of different wheat straw pretreatment methods to produce sophorolipid.LSL has poor water solubility,and the development of new LSL dosage forms will help to improve its bioavailability and expand its application potential in the field of medicine.Preparation of solid dispersion(SD)is one of the methods to improve the bioavailability of insoluble solid drugs.Therefore,searching for a suitable method and carrier to prepare LSL-SD helps to solve the problems of low dissolution and low bioavailability of LSL.At present,commonly used surfactants such as Tween-80 can cause adverse reactions such as nausea,hemolysis,even shock.ASL is an excellent biosurfactant and has the potential to be developed into pharmaceutical excipients.Investigating the ability of using ASL instead of Tween-80 to prepare two types of etoposide nanoemulsion(EN E)can help solve the problems caused by Tween-80.Based on the above considerations,this paper carried out the following three aspects of research:1.Investigate the effects of different straw pretreatment methods on the production of sophorolipids by fermentation of wheat straw saccharification solution.The three methods of acidic pretreatment method(ACP),alkaline pretreatment method(ALP)and Sulfur trioxide microthermal explosion pretreatment method(STP)were used to pretreat wheat straw,and SLs is fermented with straw saccharification solution.Among them,ACP will increase the lignin content,which is not conducive to wheat straw pretreatment.ALP and STP can effectively strip lignin.The final glucose content in the saccharification so lution of ACP,ALP and STP were 14.00,26.50,19.50 g/L,respectively,and the corresponding total SLs output were 23.70,56.80,49.60 g/L,respectively.Among the three pretreatment methods,the ALP group had the highest yield of sophorolipids,which proved that ALP is the best method for wheat straw pretreatment.LC-MS results showed that the crude SLs obtained from the fermentation of straw saccharification solution and the crude SLs obtained from the control group with glucose and oleic acid as the carbon source had the same peak time and peak shape,indicating that the two types of bottoms don’t have structural difference in the crude SLs produced under the material.That proves wheat straw has the potential to replace glucose as a cheap carbon source a nd reduce the production cost of SLs.2.The effects of different methods,carrier types and drug-carrier ratio on the dissolution and properties of LSL-SD are investigated.LSL-SD is prepared by melt-solvent method,the carrier is cellulose acetate(CA),and the drug-to-carrier ratio is 1: 2.The dissolution rate of LSL-SD is 98.50%,which is 53.50% higher than LSL API.In the same way,etoposide(ETO)solid dispersion(ETO-SD)is prepared with a dissolution rate of 80.80%,which is 30.40% higher than ETO API.Fourier infrared spectroscopy(FI-IR)shows that the peaks decrease and the peak shape broadens.Thermogravimetric(TG)and scanning differential calorimetry(DSC)show that both SD melting points and crystallinity decrease.Scanning electron microscopy(SEM)showed that the two SD structures become loose.This proves that the best method for preparing LSL-SD is the melt-solvent method,the carrier is CA,the drug-to-carrier ratio is 1: 2,and the corresponding dissolution rate is increased by 53.50 %.3.The effects of different colostrum p H and different sterilization methods on the preparation of etoposide nanoemulsion(ENE)are investigated.EN E is prepared by high-pressure homogenization method,in which the water phase is 5.00 g glycerol,4.00 m L 0.80 g/L ASL aqueous solution(or 0.20 g Tween-80),120.00 m L water,the oil phase is soybean phospholipid 3.60 g,medium chain fatty acid(MCT)20.00 m L,and soybean oil 20.00 m L.Acidic sophorolipids-etoposide nanoemulsion(ASL-ENE)and Tween-etoposide nanoemulsion(Tween-EN E)are obtained.ASL-EN E colostrum p H=5.50,ETO half-life in ASL-ENE is 32.80 h,19.00 h in the injection,the half-life is extended by 72.63% and becomes shorter with the increase of p H,proving that ASL can extend the half-life of the drug,acidic conditions are conducive to the preservation of ASL-ENE.Both particle sizes are around 205.00 nm,Tween-ENE potential is-45.10 m V,PDI is 0.19,ASL-EN E potential is-38.40 m V,PDI is 0.07.Water bath and high-pressure steam sterilization o f the two ENE are stable,and the release rate reaches more than 90% within 60 minutes.The results show that ASL has the ability to replace Tween 80 to prepare ENE,and the obtained ENE has better drug loading capacity and stability.