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Application Of Layer-by-layer Deposition Method Based On Electrostatic Action In Three Paclitaxel Nano-targeted Drug

Posted on:2021-02-03Degree:MasterType:Thesis
Country:ChinaCandidate:Q Z WangFull Text:PDF
GTID:2531306317466094Subject:Medicinal Chemistry
Abstract/Summary:PDF Full Text Request
Layer-by-layer deposition is a method of preparing a multilayer film based on static electricity and other forces.It can deposit a layer of oppositely charged polyelectrolyte on the charged surface of particles.The layer-by-layer deposition method is used to modify the nanoparticles only to modify the surface of the particles,without affecting the internal design and structure.After being covered with a multi-layer film,it can stabilize the entire system and protect the internal structure.It can extend the circulation time in the blood,and can increase the targeting ability through further modification.It has been applied to the research of various nano drug delivery systems.This subject mainly studies the application of layer-by-layer deposition method based on electrostatic effect in three drug-loading systems of paclitaxel liposome,paclitaxel albumin nanoparticles and paclitaxel hyaluronic acid micelles.In this paper,hyaluronic acid and polylysine are selected as the positive and negative polyelectrolytes as the main materials for layer-by-layer deposition of multilayer films.In this paper,first,dipalmitoylphosphatidylcholine(DPPC),cultured phosphatidylethanolamine(DSPE-mPEG2000),1-myristica-sn-glycerol-3-phosphatecholine(MSPC)and phosphatidylethanolamine-polyethylenedioxide Alcohol 2000-maleimide(DSPE-PEG2000-Mal)was used as the membrane material,and a blank liposome with a particle size of 89.1 nm and a potential of-14.0 mV was successfully prepared.The blank lipid was found by ultrafiltration centrifugation The optimal conditions for the deposition of polylysine on the body surface were obtained,and liposomes with a particle size of 95.2 nm and a potential of+15.3 mV were obtained.The modified liposomes successfully reversed their potentials and their particle size increased slightly.Modification of drug-loaded liposomes with the same method yielded similar results.Secondly,human serum albumin was used as a carrier to successfully prepare paclitaxel-encapsulated albumin nanoparticles with a particle size of 123.4 nm and a potential of-18.6mV.The surface was modified with polylysine to successfully prepare a positively charged surface Paclitaxel Albumin Nanoparticles.Finally,the paclitaxel hyaluronic acid nanomicelle PTX/HA-PTX was successfully prepared by a synthesis method and a self-assembly method,with a particle size of 116.4 nm,a potential of-19.8 mV,a drug loading of 28%,and an encapsulation rate of greater than 99%.The nanomicelle is very stable within 24 hours at 37℃ and has a slow-release effect.On the basis of the above micelles,the layer-by-layer deposition method showed that the polylysine layer was successfully modified,and hyaluronic acid and polylysine can be deposited alternately to prepare multilayer deposited nanomicelles.In addition,the E-selectin peptide ligand(CIELLQAR)was successfully covalently attached to polylysine,and the polylysine modified by the above peptide ligand was also deposited on the micelle surface,thereby further enhancing the Tumor targeting of nanomicelles.MALDI-TOF results show that 1-3 E-selectin peptide ligands are attached to each polylysine molecule.In this section,we use hyaluronic acid(HA),polylysine(PL)or peptide CIELLQAR modified polylysine(PL-CIELLQAR)as a polyelectrolyte to deposit on the surface of PTX/HA-PTX micelles 1-3 layer polyelectrolyte,successfully obtained and characterized six kinds of nano-micelles,the results show that the diameter of the above-mentioned nano-micelles are less than 200 nm,good dispersion,the potential can be consistent with the potential of the outermost polyelectrolyte,and The sealing rate is more than 98%,with good stability.Through the above research,1-3 layers of polyelectrolyte can be successfully modified by layer deposition on the surface of the three paclitaxel nano-delivery systems,which has laid a foundation for enhancing the stability and targeting of the nano-system and discovering a new nano-delivery system with better performance basis.
Keywords/Search Tags:Layer-by-layer deposition, Hyaluronic acid, Polylysine, E-selectin, Nano drug delivery
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