Structure Design And Preformance Study Of Anti-Cancer Nanocapsules With Smart Layer

Recently, in order to conquer cancer, countries are racing to develop the newest nano drug carrier material and technology. Polymer nano drug carriers have many advantages such as good biocompatibility, long circulation time in vivo and environmental response (pH, ion concentration, protease) drug release, etc. At the same time, by designing the molecular structure, the recognition and penetrating ability of nano carrier for targeted cells can be effectively improved, especially for the treatment of malignant tumor disease.But for now, there are also some limitations in applications of polymer nano drug carrier despite all the advantages listed above. The most common polymer nano carrier in research and application was polymer micelle/vesicles (amphiphilic copolymer, liposomes, etc.), which has low drug loading capacity, poor stability and the encapsulation rate, leading to antineoplastic agent prematurely leaking before the tumor site in the process of circulating. Biodegradable polymer (polylactic acid, polylactic acid and glycolic acid copolymer, poly has lactone, etc.) colloid particles have relatively high drug loading and encapsulation rate, but the period and efficiency of polymer degradation inhibit the drug release effectively.This study, based on the above considerations of the issue, aims to develop a new type of high drug loading intelligent nano drug capsule, synthesized a series of antineoplastic drugs DOX nanoparticles with high nanocrystallization, water stability and high dissolution rate via high-gravity anti-solvent precipitation. Then on this basis, by regulating the situ copolymerization of functional monomers and biodegradable crosslinking agent on the surface of the particles, we constructed intelligent nano drug capsules with high stability, cell endosome escape "proton sponge effect", whose capsule wall can be degraded and release drug timely. The effect of technological parameters of high gravity, surface active agent, functional monomer, the types and ratio of crosslinking agents on nanodrugs capsule in antitumor efficacy were studied in details, the research content is as follows:(1) DOX nanoparticles were synthesized via high-gravity anti-solvent precipitation. The nanoparticles are spheric morphology, while the shape is regular,the particle size is homogeneous and the distribution is narrow. The particle size ranges within 100 nm. The dissolution rate in vitro tests showed that the dissolution rate has been obviously improved.(2) A new, low toxicity and efficient anti-cancer drug delivery system was obtained by using prepared DOX nanoparticle capsules as delivery carrier. DOX nanoparticle capsules were prepared with acid biodegradable cdimethyl acrylic acid glyceride (GDM) as crosslinking agent. The dissolution rate in vitro tests showed that DOX nanoparticle capsules have pH response. Confocal fluorescence and flow cytometry showed that the adriamycin nanoparticle capsules in MCF-7 cell uptake.(3) By introducing positive monomer N-[3-(dimethyl amine) propyl] methyl acryloyl (APM), Zeta potential test showed that the surface of DOX nanoparticle capsules positively charged, indicating the "proton sponge effect" of DOX nanoparticle capsule.