| In recent years,the treatment of cancer has been a research hotspot.Among them,tumor-targeted multifunctional nanocarriers play an important role in tumor diagnosis and treatment,and the commonly used effective means for preparing functional nanoparticles are macromolecular self-assembly.The self-assembly of polymer micelles is superior in poorly soluble drug delivery systems.In this paper,hyaluronic acid is used as a hydrophilic segment to form nanomicelles by self-assembly with solanesol as a hydrophobic segment.Hyaluronic acid(HA)is a natural macromolecule with good biocompatibility and degradability,which has a good application prospect in many fields.However,hyaluronic acid has the disadvantages of its own hydrophilicity and single function,making its application range subject to certain limitations,so it is usually modified to change the physical and chemical properties of HA in order to give it more functions.In this paper,the active material solane thiosalicylic acid was used to modify hyaluronic acid,and it self-assembles into micelles in water,and its series of characterization and antitumor efficacy were investigated.1.Synthesis and characterization of hyaluronic acid micelles of grafted solanesol derivativesFirst,solanesol and thiosalicylic acid are formed into a solane thiosalicylic acid through a thioether bond,and hyaluronic acid and adipic acid dihydrazide are linked by an amide bond to obtain hyaluronic acid adipic acid dihydrazide(HA-ADH),which re-ligating with the previously synthesized solane thiosalicylic acid through an amide bond,the target product HA-STS was successfully obtained.The successful synthesis of HA-STS was confirmed by infrared spectroscopy and nuclear magnetic characterization.The synthesized carrier material is self-assembled into micelles in water,and DOX is loaded to obtain drug-loaded micelles.Characterization by laser particle size analyzer showed that the particle size and PDI value of the blank and drug-loaded micelles were small,and all of them were uniform spherical structures.The drug-loaded micelles have a drug loading of about 6.0% and a relatively high drug loading.Both dilution stability and storage stability are good.Differential calorimetric scanning analysis(DSC)demonstrated that doxorubicin exists in amorphous form in polymer micelles.In vitro release studies have shown that the polymer micelle HA-STS-DOX has the characteristics of slow release of the drug,and the release amount is high in an acidic environment,reaching about 70%,and the release amount under neutral conditions is less than 40%.In vitro hemolysis experiments showed that the hemolysis rate of blank and drug-loaded micelles on red blood cells was less than 5.0%,which was consistent with the requirements of intravenous injection.2.Efficacy evaluation of hyaluronic acid-loaded micelles grafted with solanesol derivativesThe MTT experiment proves that the blank micelle material has certain anti-tumor effect.Compared with STS,the cytotoxicity of HA-STS is relatively small.It may be because the polymer micelles encapsulate hydrophobic active groups and the hydrophilic chain is longer,thereby reducing cytotoxicity.The cytotoxicity of the drug-loaded micelles was stronger.Compared with 24 h,the cell inhibition was stronger at 48 h,indicating that the cell inhibition intensity was time-dependent.In vivo anti-tumor experiments have shown that the drug-loaded micelle HA-STS-DOX has the smallest tumor volume and the least toxicity of cardiotoxicity and liver,which fully demonstrates the advantages of drug-loaded micelles in anti-tumor. |
PDF Full Text Request