Doxorubicin - Hyaluronic Acid Nanoparticles On The Role Of Oral Squamous Cell Research

[Objective]This study was designed to prepare the drug loaded adriamycin hyaluronic acid nanoparticles and investigate its targeting ability and cytotoxicity in vitro and athymic mouse[Methods]The first part:the chemical conjugates HA with DOCA.The self-assembled HD nanoparticles solution was obtained by sonication.The formation of HD nanoparticles was characterized by transmission electron microscopy(TEM).ADM was used as a model drug to prepare drug-loaded nanoparticles.Investigate the drug release profile with different feed weight ratio of ADM. The second part:human cultured oral squamous cell was exposed to different concentrations of adriamycin loaded nanoparticles(0.5,1.0,5.0,10.0μg/ml).MTT assay was used to detect the targeted cytotoxicity of adriamycin loaded nanoparticles.With the concentrations of 5.0 and 10.0μg/ml,6,12,24and 48 hours later cell apoptosis was ascertained by cell flow cytometry.The third part:36 athymic mouse burdened with oral squamous cell were randomly divided into 2 groups.Group A was treated with adriamycin and group B treated with drug-loaded nanoparticles.With adriamycin concentration of 1.0,10.0μg/ml were administered respectively to subjects through the tumor.The dose was 1mg/kg for each group.1,5 and 15 hours after administration,3 subjects were sacrificed and the normal tissue,carcinoma tissue,heart,liver,spleen and kidney were examined through high performance liquid chromatography(HPLC) to identify drug concentration.[Results]1.The TEM observation demonstrated the self-assembled HD nanoparticles are near spherical shape.The drugs different feed weight ratio release obviously in first 5 hours,then it became mild.2.When oral squamous cell were treated with adriamycin nanoparticles in different concentrations,cell apoptosis was induced.The cytotoxicity of adriamycin loaded nanoparticles was greatly enhanced as compared with free adriamycin by MTT method(p<0.01),.The results of cell flow cytometry show that the rate of cell apoptosis is enhanced with the increase of the time(P<0.01).The percentage of cell apoptosis in the same time is increased with the increase of concentration(p<0.01). 3.The drug concentration in the carcinoma in group B were significantly higher than those in group A (P<0.01).The drug concentration in heart,liver,spleen,and kidney of group B were significantly lower than those of group A(P<0.01).[Conclusion]1.The drug in nanoparticles partially crystallized at higher drug content enhanced the sustained release.2.Nanoparticles based on HA as drug carriers can specifically recognize oral squamous carcinomas cells and deliver adriamycin into the cells and the effect is enhanced by the time.3.The drug-loaded nanoparticles can reinforce the target - specific action of anticancer agent, increase the drug concentration within the lesion and decrease it in non- specific organs.