Preparation And Application Of Glucose Ester And Trehalose Ester Nano-drug Carriers

Malignancies are one of the leading causes of death worldwide.Chemotherapy has become one of the main methods for treating cancer because of its high efficiency.However,conventional chemotherapeutic drugs suffer from several limitations,such as poor solubility,relatively short half-life and low tumor accumulation.Nanotechnology have developed rapidly in recent years.Loading small molecule chemotherapeutic drugs on nanocarriers has the advantages of improving the solubility of drugs,prolonging residence time in blood circulation.In addition,nanomedicines can passively target and accumulate in tumor by EPR.However,a lot of carriers with low drug loading capacity and may cause side-effects to kidneys and other organs in the course of degradation and metabolism.Carbohydrates are ideal drug carriers because of good biocompatibility and biodegradability.Here,hydrophilic glucose and trehalose were connected to hydrophobic oleic acid through p H-sensitive ester bonds,and glucose-oleic acid and trehalose-oleic acid nanomicelles were constructed and used to transport the hydrophobic drug podophyllotoxin.This work is shown as following:First,hydrophilic glucose and hydrophobic oleic acid are connected through p H-sensitive ester bonds to construct amphiphilic glucose oleic acid monoester.Due to its amphiphilic property,it can self-assemble to nano-micelles in water and is used to load the hydrophobic podophyllotoxin.The nano-micelles were spherical and the particle size was about 58 nm by TEM and DLS measurements.Cumulative release experiment showed that podophyllotoxin-containing glucose oleic acid monoester nano-micelles can release up to50% at p H=5.5,while at p H=7.4 only 21% drug can be released for 50 hours.And it is very stability under the physical conditions.Cytotoxicity and cell phagocytosis showed that prepared micelles had good biocompatibility and could be quickly taken up by cancer cells.Cytotoxicity of drug-loaded micelles showed that drug-loaded micelles significantly reduced viability of tumor cells compared to free podophyllotoxin.Second,trehalose monoester and trehalose diester were synthesized with a p H sensitive ester group using TBTU method.Due to the amphiphilic molecular structure,trehalose monoester and trehalose diesters can self-assemble to nano-micelle in water.Then,trehalose monoester was used for podophyllotoxin loading.TEM and DLS measurements showed that the micelles were spherical and the particle size was about 81 nm and 155 nm,respectively.The podophyllotoxin was loaded by film dispersion method,and the rate of drug encapsulation was about 66.8%.The cumulative drug release experiment showed that the nano-drug was of p H response ability,and the drug can rapidly release in acidic environment.The cytotoxicity experiment showed that the blank micelles had a good biocompatibility and the drug loaded micelles presented an excellent anticancer activity.