Study On Antitumor Effects Of β-elemene Polymeric Micelles In Vivo And In Vitro

Cancer is a major public health issue in the w orldwide.Many researches revealed theβ-elemene,a volatile oil extracted from the curcuma wenyujin,can cure various cancers,including lung cancer,liver cancer,cerebral cancer,breast cancer,ovarian cancer,etc.However,Due to the terrible water solubility and poor bioavailability,mainliningβ-elemene induces a series of side effects,as phlebophlogosis,hemorrhage and pain to restrict the clinic application.Under this project topic,we preparedβ-elemene polymeric micelle,not only do we overcome the defects as poor bioavailability and side effect lead by mainliningβ-elemene,but the polymeric micelle boosts up the antineoplastic effect on the mice models.The main research contents of this paper are as follows:1.The synthesis and characterization of mPEG-PCL:compound the segmented copolymer by the ring opening polymerization,ascertaining the chemical construction by H-NMR;2.The quality research of nano-micelle:study the particle size,Zeta potential,drug-loading capacity,in vitro release behavior and stability of the micelle.3.The research of active antineoplastic effect onβ-elemene micelle on the cellular level:test the cytotoxicity of drug-loading micelle;detect the apoptosis and cell cycle of C26by Annexin V-FITC/PI reagent and PI staining.We replace theβ-elemene by coumarin and measure the capacity that C26 cell uptake micelle by FCM（flow cytometry）and IF（immunofluorescence）.Simultaneously,we measure the content ofβ-elemene micelle to assess the capacity that cell uptake micelle by HPLC.And we inspect the anti-metastasis capacity of micelle by wound healing.4.The research ofβ-elemene micelle on the animal level:experiment the pharmacokinetics test,in vivo anti-colon cancer test and the partial stimulation test.The conclusion of this paper is:the morphology of micelle is uniformly spherical,homogeneous distribution and high encapsulation efficiency.The diameter of the micelle is 20.96mm.Drug release effect is continuous and controllable.Comparing to the freeβ-elemene,theβ-elemene micelle has higher anti-proliferative activity,induces more apoptosis and cell cycle arrest,and strengthens the capacity of cell to uptake the drug.Meanwhile,theβ-elemene micelle improves the drug stability in the serum.A pharmacokinetics research revealed that the micelle groupβ-elemene’s AUC is 1.78times higher than freeβ-elemene and T_1/2/2 is 1.61 times.Proving the cycling time is extended and the drug concentration is higher.On the mice model of the colon cancer,theβ-elemene micelle has great antineoplastic effects,presents dose-dependent and no major toxic effect on normal organs.According to the partially simulation experiment,comparing to the free drug,β-elemene micelle alleviated the simulation on the vessel and muscle around the injection site prominently.By and large,we prepared mPEG-PCL polymeric micelle loadedβ-elemene,this micelle would be a new delivery system forβ-elemene and,play a great role in the future clinic treatment.