Preparation,Characterization And In Vitrocy Totoxicity Of Docetaxel,Curcumin Nanoparticles Based On New Dendrimer

Curcumin extracted from the rhizome of zingiberaceae plants turmeric is a kind of yellow pigment.It is an acidic polyphenols,the main chain is unsaturated aliphatic and aromatic group.Curcumin is the main active ingredient of turmeric,it is not onlyadvantageous bravery,antibacterial,fall hematic,anticoagulation,antioxidant effect,it is reported that curcumin has obvious anti-cancer effect.Curmumin plays a role of anti-cancer by inducing the differentiation of malignant cells,inducing apoptosis of tumor cells and inhibitory effect of tumot growth.And Curcumin is widely used in clinical.Nanosuspension as a new nano-delivery system draws the attention of thr public,because its preparation method is simple,widely used,the most important is poorly soluble drugs with high drug loading and drug transfer efficiency,especially suits for relatively weak activity,slightly larger dose of medicine chemical units or active site.Nanosuspensions have proved to be one of the most effective ways to deal with the dissolution problem of insoluble drugs with the advantage of very high drug payload and benefiting the biodistribution improvement of hydrophobic drugs.In this study,we using solvent precipitation in combination with high pressure homogeneous method preparation CUR nanosuspensions,improve the drug loading ang increase the speed of drug absorption and absorption rate,enhance biovailability.The main contents include the preparation,characterization,in vitro release.The CUR-PGD nanoparticles were prepared via the method of ultrasound precipitation combined high-pressure homogenization using codendrimer PAMAM-co-0.25OEG(PGD)as stabilizer.The drug loading capacity(DL%)of CUR-PGD nanoparticles was 41.2%,the solubility of CUR was increased to 1.5 mg·mL-1(50 times of CUR bulk powder).The mean diameter of the nanoparticles was 438.0 nm with spherical morphology and the zeta potential was 41.4 mV.The stability of CUR-PGD nanoparticles was measured in physiological saline,glucose,PBS and plasma,and the result showed that the nanoparticles was stable in these medium and there was no hemolytic phenomenon,which means they were suitable for intravenous administration.The DSC and XRD spectra of CUR-PGD nanoparticles showed that the CUR was present as crystal morphology in the nanoparticles.The CUR release from nanoparticles was detected in different release medium and presented obvious controlled release behavior.In summary,these results suggested that PGD may be an effective stabilizer for the preparation of CUR-PGD nanoparticles and CUR-PGD nanoparticles are a promising drug delivery system for CUR application in clinic.Docetaxel is a new generation of taxanes semisynthetic anticancer drugs,in clinical trails,has been successfully applied,mainly for the treatment for ovarian cancer,post-breast,lung and head/neck cancer.But docetaxel is highly lipophilic,insoluble in water,poor oral absorption,and unstable,low bioavailability.In this study,we using solvent precipitation in combination with high pressure homogeneous method preparation DTX nanosuspensions,improve the drug loading ang increase the speed of drug absorption and absorption rate,enhance biovailability.The main contents include the preparation,characterization,in vitro release,cytotoxicity test.The DTX nanoparticles were prepared via the method of ultrasound precipitation combined high-pressure homogenization using codendrimer PAMAM-co-0.25OEG(PGD)as stabilizer.The drug loading capacity(DL%)of DTX-PGD nanoparticles were65.7%,the solubility of DTX was increased to 1.6 mg·mL-1.The mean diameter of the nanoparticles was 270.4 nm,the PDI was 0.128 and the zeta potential was 28.6 mV.The DTX-PGD nanoparticles were stable in glucose and plasma.The nanoparticles exhibited schistose morphology in SEM.The XRD spectra of DTX-PGD nanoparticles showed that DTX was present as crystal morphology in the nanoparticles.The release of DTX from nanoparticles was detected in PBS+0.5%SDS release medium and presented obvious controlled release behavior.There was no hemolytic phenomenon which means they were suitable for intravenous administration.MTT results showed that the nanoparticles exhibited higher cytoxicity for 4T1 cells compared with DTX solution.