| The delivery of chemotherapeutic can be improved by drug delivery systemsusing therapeutic nanocarriers, including liposomes, micelles and polymericnanoparticles. To be safe, these drug delivery systems are supposed to possess highloading capacity, accumulate in the required sites and extend circulation time.Additionally, comparing to other delivery systems, the polymeric nanoparticles havemany advantages, less expensive and the manufacturing processes are simple andsuitable for industrial scale up, although the use of organic solvents may make theissues toxic. Among the polymeric nanoparticles, biocompatible and biodegradablepoly (d,l-lactic/glycolic acid)/(PLGA)-based nanoparticles has been studied as carriersfor therapeutic bioactive molecules. Since PLGA have been investigated for manyyears and is approved by the US Food and Drug Administration.Poly (ethylene glycol)(PEG) with hydrophilic, uncharged and non-immunogenicproperties is an attractive material. Because it’s easy for surface modification of thenanoparticles to reduce opsonization. PLGA nanoparticles with PEG grafting escaperenal exclusion; Moreover, the long-term cycle nanoparticles preferentiallyaccumulate in tumor tissue and inflammation by enhancing the effect of permeabilityand retention (EPR). This stealth capacity of PEG depends on parameters, such as thedensity, molecular weight, conformation and flexibility of the PEG chains. In addition,the biological dispersion properties of PLGA are influenced by particle size, theinfluence of the conditions such as the loss rate of PEG. Compared with otherlong-term circulation system, the main advantage of PEG nanoparticles is shellstability and its ability to control drug release.In this article, we designed four different molecular weight proportion of theMPEG-PLGA parcel antitumor drug10-hydroxy camptothecin (10-HCPT) to formnanocarrier. And carries on the micellar carrier fluid dynamics (DLS), infrared (FITR)characterization, were determined for the drug loadings, the coating rate, to study thedrug release and degradation situation in vitro, finally also to observe the anti-tumoreffect is studied. Preliminary observation and analysis on the parents of the block copolymer formed in the nanocarrier, molecular size and hydrophilic block andhydrophobic block ratio affect the above properties.We successfully synthesized four different MEPG (5k)-PLGA (3k), MPEG(5k)-PLGA (9k), MPEG (5k)-PLGA (11k) and MPEG (5k)-PLGA (16k) blockcopolymers, through the dialysis method successfully loaded10-HCPT. Among them,the MPEG (5k)-PLGA (9k) to form micelles has the highest drug loadings, MPEG (5k)-PLGA (11k). Each particle size, uniform dispersion is good. In vitro release behavior,the MPEG (5k)-PLGA (11k) for drug release kinetics experiments, is the optimalgroup. In its first phase, and interpretation of the most obvious until36h total releasequantity reached89.13%, and then continue to release to the72h, drug releasequantity of91.06%in the end. On the slow release behavior and cumulative releasequantity are the best in the four groups. Also in the process of in vitro release, thegreater the proportion of hydrophilic block MPEG, PBS medium pH declined more.And in this process, the molecular weight of the size of nanocarrier micelle basic didnot change obviously, only appeared in the nanocarrier surface cracks. MPEG(5k)-PLGA (16k) in the process of degradation into small fragments, the speed shouldbe the slowest, and the smaller the MPEG than column, the slower the materialdegradation. Nanocarrier in the process of releasing quality change instead ofhydrophilic block and hydrophobic block of different proportion. And with thepercentage of the MPEG reduced, such a decline in the rate of mass loss, and the totalquality loss. Four kinds of carriers in vitro antitumor effect also have differences,including the MPEG (5k)-PLGA (9k) formation of the micelle showed strong abilityof tumor destruction, then MPEG (5k)-PLGA (11k). |
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