The Study Of Curcumin MMP-2 Sensitive Targeting Drug Delivery System

Curcumin has a clear anti-tumor activity and good safety.However,the clinical application of curcumin was seriously limited by its poor water solubility,instability,short half-life in vivo and low bioavailability.The common dosage form of curcumin can not reach the purpose of cancer treatment because of the low bioavailability.With the development of the materials chemistry,nanotechnology and nanomedicine,amphiphilic polymer nanoparticles can be used as drug carriers due to its appropriate particle size,shape and high drug loading.After designed to drug delivery system,it was effectively solubilizing hydrophobic drug and to improve drug stability which attracts the concern of researches.Especially the environment sensitive tumor targeted drug delivery system which was designed according to the tumor microenvironment,it can significantly improve the bioavailability of drugs,and achieve targeted drug delivery.Polysaccharide has anti-tumor activity by itself.In this study,we choose Carboxymethyl dextran（CMD）substitute PEG as hydrophilic segment,hope it could combine the advantages of PEG and its own.amphiphilic triblock copolymer（CMD-Peptide-PCL,CPP）was synthesized using CMD,polycaprolactone（PCL）choosed as hydrophobic segment,MMP-2 sensitive peptide（XGPLGIAGQr₉X）as bridge.Then CPP assembled into nanoparticles.Curcumin,choosed as a model drug,was loaded by physical embedding method to prepare curcumin-CPP nanoparticles（Cur-CPP NPs）.Meanwhile,CPP was added as a functional material into the base film material of liposomes to prepare curcumin-CPP liposomes（Cur-CPP Lips）.Finally,the quality of Cur-CPP NPs and Cur-CPP Lips were evaluated by characterize the particle morphology,particle size,particle distribution,Zeta-potential,encapsulation efficiency and drug loading.Hydrophilic segment,hydrophobic segment and triblock copolymer were mainly characterized by FT-IR,¹H-NMR and GPC.The molecular weight of CMD was 11266,PCL was 3764.PDI was 1.24 and 1.05.¹H-NMR spectrum of the triblock copolymer and the GPC analysis revealed the successful preparation of amphiphilic triblock copolymer.The quality assessment of Cur-CPP NPs and Cur-CPP Lips have showed that the spherical shapes of Cur-CPP NPs and Cur-CPP Lips were observed by TEM.Cur-CPP NPs and Cur-CPP Lips’average size was362.7 nm and 2.014μm,PDI was 0.369 and 0.077,Zeta potential was-2.83m V and 16.6 m V.The encapsulation efficiency of Cur-CPP NPs and Cur-CPP Lips was determined as 87.46%and 99.33%and the drug loading as 0.8396%and 1.82%by HPLC.In addition,the inhibitory effect of different concentrations of Cur-CPP NPs and Cur-CPP Lips to the growth of Hela cell were investigated.The results showed that Cur-CPP NPs have no inhibitory effect to the growth of Hela cell.The concentrations of 4,16μg/m L Cur-CPP Lips have ability of inhibiting the Hela cell’s growth,and a high concentration（16μg/m L）of Cur-CPP Lips significantly inhibited the growth of Hela cell.（P<0.05）.Meanwhile,the blank vector CPP Lips at high concentrations（16μg/m L）has a certain ability to inhibit to Hela cell’s growth,but lower than the same concentration of Cur-CPP Lips.