Preparation And Evaluation Of PEG-graft-PLA Nanoparticles As Drug Delivery System For Hydrophobic And Hydrophilic Medications

The duration of medicines transported to the pathological site varies greatly due tothe difference of its physicochemical properties, which leads to the combination therapyimpossible. However, the physicochemical properties of medicine only relate to thenanoparticles’ surface properties after encapsulated into nanoparticles (NPs). Thepresent study aimed at the encapsulation of both hydrophobic and hydrophilicmedications with polyethylene glycol-graft-poly (lactic acid)(PPLA) so that thedeveloped delivery system could arrive at the same pathological site and realizecontrolled release and combination therapy.The main contents of this research were shown below:Firstly, a nanoscale delivery system for hydrophilic drugs was developed usingnewly synthesized PLA derivative polymer PPLA by way of self-assembly. NPs wereprepared by solvent evaporation techniques with insulin (INS) as model drug. The NPswere characterized in terms of morphology, particle size distribution, zeta potential,hemolytic activity, the encapsulation and release of insulin. In particular, the bioactivityof the insulin released from nanoparticles was investigated. The results demonstratedthat the insulin encapsulated NPs (INS-PPLA NPs) were spherical with mean diameterof214nm, mean zeta potential of-34.65mV and hemolysis rate far below the ChineseHemolytic Standard of Injection Drugs (that is5%). The entrapment rate of insulin was60.7%and the release could be well controlled and lasted for24h. Furthermore, thereleased insulin retained its bioactivity. The results suggested that the PPLA NPs had thepotential for hydrophilic drugs carriers.Secondly, a nanoscale delivery system for hydrophobic drugs was developed usingPPLA by way of self-assembly. NPs were prepared by solvent evaporation techniqueswith Cucurbitacin B (CucB) and Docetaxel (TXT) as model drugs. The NPs werecharacterized in terms of morphology, particle size distribution, zeta potential,hemolytic activity, the encapsulation and release of CucB and TXT. The resulting NPswere narrowly distributed and spherical with average particle size around180nm, Zetapotential exceed–15mV and encapsulation efficiency over50%. The NPs realizedcontrolled release of hydrophobic medications for over160h with good bloodcompatibility.Thirdly, the viability of live cancer Hep-2cells and normal endothelium cells treated with CucB, TXT, CucB-PPLA NPs, TXT-PPLA NPs, and CucB in combinationwith TXT, CucB-PPLA NPs in combination with TXT-PPLA NPs respectively wasevaluated using MTT assay. The results demonstrated that both the CucB and TXTinhibited the growth of live cancer Hep-2in vitro; CucB in combination with TXT hadaddictive or synergistic antitumor activity against Hep-2in vitro; The encapsulationincrease the inhibition of medicines to Hep-2cells no matter in single and incombination medication. In addition, PPLA NPs reduced the side effects of anticancerdrugs to normal endothelium cells.