Study On Preparation And Properties Of PHBV And Dextran Based Nano Drug Delivery Systems

Polymer nano-drug delivery system has attracted considerable attention because of its ability to enhance bioavailability and reduce side effects of chemotherapy drugs.Poly(3-hydroxybutyric-co-3-hydroxyvaleric)(PHBV)is a biodegradable,non-toxic bacteria produced polymer,which is an emerging biomaterial used as delivery systems of hydrophobic drugs.However,pure PHBV nanoparticles would be fast clearanced by reticuloendothelial systems(RES)due to the lipophilicity of polyester.To insure PHBV nanoparticles being transported to tumor tissues without unexpected degradation,it is necessary to enhance hydrophilcity of PHBV by surface modification,through which blood residence time,tumor targeting by permeability and retention(EPR)effect of PHBV can be increased or enhanced and thus improving curative effect of chemotherapy.In the present work,we choose dextran,for its excellent biocompatibility,to improve PHBV's hydrophilcity.On top of that,two different dextran-modified PHBV amphiphilic nano-drug delivery systems were constructed.In the first system,a novel PHBV/dextran amphiphilic nanoparticles(PDNPs)drug delivery system was formulated via an original double emulsion(w1/o1/w2)solvent-evaporation method.Results showed that the mean diameter of PDNPs was 205.0±6.9 nm and their zeta potential was-1.59±0.12 mV,by using dynamic light scattering(DLS)detection.PDNPs showed obvious core-shell structure with uniform particle dispersion.Cisplatin was loaded to demonstrate characterizations of the drug delivery system.Release time was prolonged up to 7 days according to in vitro drug release profile of cisplatin from PDNPs with 19.3±2.9%of drug loading content(DLC).We also found that it could be released faster in cancer cells(pH=5.5)than in normal cells(pH=7.4)with phosphate buffered saline(PBS)in PDNPs drug delivery systems,indicating that PDNPs were pH-responsive with excellent slow-release performance.The colony forming assay manifested that PDNPs displayed no cytotoxicity,still cisplatin-loaded PDNPs exhibited higher killing efficiency to cancer cells when compared with normal cells,which were represented by HeLa and L02 cell lines respectively,indicating that PDNPs delivery systems can specifically recognize cancer cells.In the other system,Dextran-grafted PHBV(PHBV-g-Dex)was synthesized successfully via an esterification reaction,and the PHBV-g-Dex micelle drug delivery system was fabricated by self-assembly behavior.As a result,the critical micelle concentration(CMC)was 0.029 mg/ml detected by fluorometry using pyrene as a probe.The mean diameter of PHBV-g-Dex micelles,which appeared spherical morphology and uniform dispersion,was 89.3±14.6 nm and their zeta potential was-20.5±3.2 mV.The hours of in vitro cisplatin release from PHBV-g-Dex micelles with 12.1±2.4%DLC could be prolonged to 72 h.We found that it could be released faster in cancer cells(pH=5.5)than in normal cells(pH=7.4)with PBS in PHBV-g-Dex micelles,which demonstrated PHBV-g-Dex micelles were pH-responsive with good slow-release performance.The colony forming assay manifested that PHBV-g-Dex micelles displayed no cytotoxicity.And cisplatin-loaded PHBV-g-Dex micelles exhibited higher killing efficient to cancer cells compared with normal cells,which indicated PHBV-g-Dex micelles delivery systems can specifically recognize cancer cells.In conclusion,through improving hydrophilcity by dextran modified PHBV,the novel PHBV/Dex nanoparticles and PHBV-g-Dex micelles drug delivery systems exhibit their own advantages as nano-delivery systems,both systems can be potentially applied for cancer chemotherapy to improve curative effect and reduce side effects.