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Research On The Preparation Of An Intelligent Drug Delivery System Based On Human Hair Keratin

Posted on:2022-04-27Degree:MasterType:Thesis
Country:ChinaCandidate:J S DuFull Text:PDF
GTID:2511306722482554Subject:Chemical Engineering
Abstract/Summary:PDF Full Text Request
Drug delivery system(DDS)can reduce the serious side effects of chemotherapy in cancer treatment.The method of building a safe and effective DDS has been widely concerned by academia in recent years.Nanoscale DDS with good biocompatibility and stimulus response can accumulate in tumor tissue through passive targeting during human circulation and release loaded drugs through stimulation in tumor microenvironment.Human hair keratin is a kind of human natural polymer materials.Compared with other non-human materials,human hair keratin basically does not produce immune response after entering the human body and has good biocompatibility.In addition,human hair keratin also has natural stimulus response,excellent biological activity and biodegradability.Based on this,according to the excellent physical and chemical properties of human hair keratin,several DDSs were designed and constructed,as follows:(1)Preparation of keratin sulfhydryl self-crosslinking DDS.There are a large number of sulfhydryl groups in the molecular chain of human hair keratin.Keratin molecules are gathered by anti-solvent method,and the sulfhydryl groups on the molecular chain are cross-linked to form disulfide bonds to prepare keratin sulfhydryl self-crosslinking DDS.The preparation method is green and non-toxic and does not add any cross-linking agent.The particle size and surface morphology of keratin sulfhydryl self-crosslinking nanoparticles were characterized by laser particle size analyzer and transmission electron microscope(TEM).The results show that the particle size is about143.9 nm and the spherical morphology and size distribution are uniform.(2)Preparation of keratin-Dopamine self-assembled DDS.Inspired by marine mussel adhesion protein,keratin-dopamine self-assembled DDS was prepared by using human hair keratin and dopamine-like adhesion protein.The preparation process is convenient and fast,and the reaction conditions are simple and easy to realize.The laser particle size analyzer showed that the DDS had stimulus response in the simulated tumor cell environment.(3)Preparation of keratin-Tannic acid complex DDS.Using plant extract tannic acid and keratin as materials,keratin-tannic acid complex DDS was prepared by hydrogen bonding and hydrophobic interaction.Due to the existence of tannic acid,the DDS has the advantages of stability and safety.The dialysis bag method was used to explore the drug release behavior of the DDS.The results showed that the drug release of the DDS was low in the simulated normal physiological tissue environment,and the double responsive drug release could be carried out in the simulated tumor cell environment.(4)Preparation of Keratin@PDA@MSNs double-response DDS.Keratin-dopamine conjugate was used to encapsulate drug-loaded MSNs to prepare a drug-loaded DDS with keratin as the "gatekeeper" and capable of double responsive drug release.The effects of the DDS on the toxicity of doxorubicin(DOX)and the growth of tumor cells was evaluated by MTT assay.The results showed that it could weaken the toxicity of DOX to normal cells and effectively inhibit the growth of tumor cells.(5)Preparation of Keratin@aminated MSNs dual-response DDS.MSNs and human hair keratin were modified,and Keratin@aminated MSNs dual responsive DDS was prepared by amidation.The serum stability test is used to test whether the DDS can be stable in the blood environment,and the results show that it can exist stably in the serum environment and has the basis for long-term blood circulation.(6)Preparation of Keratin@Cu-MOFs nano-catalysis and triple-response DDS.Cu-MOFs are fired by hydrothermal method,and Keratin@Cu-MOFs,a DDS capable of nano-catalysis and triple responsiveness,is prepared by amidation reaction.UV-vis spectrophotometer was used to verify that the DDS could catalyze the production of highly toxic reactive oxygen species through Fenton-like reactions.Laser particle size analyzer and dialysis bag method were used to verify that the DDS had triple stimulus response of pH,GSH and Trypsin.
Keywords/Search Tags:Keratin, Drug delivery system, Stimuli responsibility, MSNs, MOFs
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