Study Of Loading And Releasing Ploymer Antitumor Drugs Based On Novel Silicon Carrier

Cancer has always been one of the major diseases that threaten human health..Chemotherapy is a common strategy for cancer treatment,and the results are unsatisfactory because of the low targeting and relatively serious side effects of anticancer drugs.To overcome these problems,several nanocarriers have been developed,such as polymer based nanoparticles,liposomes,drug conjugated particles,micelles,and the like,to improve drug delivery levels.Due to the synergistic effect of nanomaterials,it also has great appeal for combined drug delivery,minimizing the toxicity of single drugs to normal cells,and inhibiting multi-drug resistance in tumor cells.Nanoparticles?NPs?have many advantages,such as high loading capacity for drugs,adjustable physicochemical properties and flexible modification,making nanoparticles suitable for encapsulating anticancer drugs,thereby improving drug solubility and in vivo behavior,and stability.In addition,surface modification of NPs can prolong their circulation in the blood and provide specific targeting to increase efficacy while reducing adverse effects.However,there are still many conditions that limit the nanoparticles to make it impossible to meet clinical expectations.This includes most NPs being recognized by the immune system and eliminated as foreign substances.At the same time,a new type of silicon carrier that can be degraded by organisms has emerged,which has caused us great concern.Silicon supports are very effective for this co-delivery system due to their good chemical surface modification,large surface area and porous structures supporting nucleic acids and drug encapsulation.Loading and release assays were performed to assess the performance of the nanoparticles?NP?as a delivery system.Key parameters of an effective drug delivery system include drug loading capacity.The loading and adsorption of the drug in the pores of the nanoparticles and their release are controlled by a lot of factors that can be adjusted to successfully load and release different types of drugs.In recent years,polymeric materials have been widely used in biology and medicine to deliver drugs,peptides,proteins or nucleic acids to target sites via polymeric materials.Many biodegradable and biocompatible micelles have been extensively studied to produce diblock,triblock or multiblock copolymer micelles,which enhance the permeability and retention effects of the drug.They provide controlled release and improved tumor bioavailability.Among them,poly?lactic-co-glycolic acid??PLGA?nanocarriers show great promise,characterized by its biocompatibility,therefore,mPEG-PLGA nanoparticles can be used as an effective drug carrier while delivering hydrophilic Sexual and hydrophobic drugs to enhance anti-tumor effects.These nanomaterials have attracted great attention due to their unique core and shell assembly,nano-size and spherical structure,and have been widely used for drug delivery,known as nanoscale drug delivery systems?nano-DDS?.The core includes a composition for loading a hydrophilic drug,the outer shell of which contributes to pharmacokinetic activity in a biological medium in vivo or in vitro.In addition to being nanosized,DDS should also have the ability to filter through the reticuloendothelial system?RES?or the kidneys to absorb substances known to be used to clear smaller particles in the body.Paclitaxel?PTX?is a semi-synthetic plant alkaloids,mainly isolated from the bark of the yew,Food and Drug Administration to obtain approval of such a chemotherapeutic agent.Paclitaxel blocks the mitotic pathway in cell division by triggering cell microtubules and triggers apoptosis.Paclitaxel blocks the mitotic pathway in cell division by triggering cell microtubules and triggers apoptosis.It is an important treatment for breast cancer,head and neck cancer,non-small cell lung cancer,ovarian cancer and AIDS-related Kaposi's sarcoma.Despite its clinical popularity in treating life-threatening cancer clutches,extreme water solubility severely limits the use of this chemotherapeutic drug.Nanoparticle colloid delivery systems constitute a new approach with improved drug delivery options and tumor targeting that removes most of the limitations of conventional chemotherapy.The addition of biodegradable and biocompatible polymers,combined with the choice of surface functionalization,provides a unique perspective associated with and interacting with the tumor microenvironment,this interaction of the nanoparticle carrier with the cancer cell results in a cytotoxic effect of the chemotherapeutic agent interacting with the intracellular organelles without producing non-specific toxicity to normal cells.Therefore,the unique structure of modern nanocarriers is considered to be the main platform for PTX delivery because it overcomes the following limitations:First,when embedded in lipid-based nanocarriers,solubility can be greatly increased,or with water-soluble polymerization.Binding,second:Since the nanoscale range of the EPR effect is 10-200 nm,these carriers can escape the recognition of endogenous RES and improve the efficacy by delivering the drug to the target site.Third:Increase tumor uptake by attaching specific functionalized ligands to actively target specific cancer cells while reducing systemic cytotoxicity and increasing the maximum tolerated dose.But there are other factors that need to be considered,including drug release patterns,stability of embedded drugs,biological interactions and targeted behaviors,and molecular mechanisms of cell signaling and safer delivery.This paper is mainly composed of the following parts:1.Synthesis of Boc-GFLG-PTXThe paclitaxel was modified by esterification of the hydroxyl group?-OH?in the paclitaxel with the carboxyl group?-COOH?of the glycine C-terminus in the tetrapeptide GFLG?glycine-phenylalanine-leucine-glycine?.Under the reaction conditions of nitrogen protection,a solution of a condensing agent DCC?dicyclohexylcarbodiimide?was added dropwise to initiate polymerization,and a catalyst DMAP?4-dimethylaminopyridine?was added to accelerate the reaction.Since paclitaxel is poor in hydrophilicity,DMF?dimethylformamide?having a relatively strong polarity is selected as a solvent in the reaction system.The structure of Boc-GFLG-PTX was determined by ¹HNMR,FTIR and mass spectrometry,confirming the success of the synthesis.2.Synthesis of polymer-loaded microspheres MePEG-PLGAAccording to the literature report,the block copolymer MePEG-PLGA was synthesized by solution polymerization,and stannous octoate[Sn?Oct?₂]was used as a catalyst.According to the pre-designed molecular weight,Select methoxy polyethylene glycol 2000 as block copolymer macro initiator.Under the protection of nitrogen,the target product MePEG-PLGA was synthesized by ring-opening polymerization of DL-lactide and glycolide,and its structure was further confirmed by ¹HNMR and FTIR.The surface morphology,size,and the like were observed by a transmission electron microscope.3.MePEG-PLGA loading of Boc-GFLG-PTXThe hydrophilic chain in the MePEG-PLGA we synthesized is the polyethylene glycol end,and the PLGA formed by the reaction of lactide and glycolide is the hydrophobic end.Therefore,under ultrasonic conditions,MePEG-PLGA can self-assemble into a sphere in water and has a core-shell structure.And when the MePEG-PLGA self-assembled into a ball,the synthesized drug Boc-GFLG-PTX was wrapped into the microspheres.We evaluated the loading of Boc-GFLG-PTX in MePEG-PLGA at different concentrations.The main method of detection was HPLC,firstly,a standard curve of paclitaxel was then measured at different concentrations of Boc-GFLG-PTX loading rate of MePEG-PLGA,select the optimal loading concentration.4.Loading of the silicon carrier to MePEG-PLGA@Boc-GFLG-PTXThe nano drug-loaded microspheres MePEG-PLGA@Boc-GFLG-PTX was loaded into a silicon carrier by an equilibrium adsorption method.Scanning electron microscopy shows that the silicon carrier is not loaded with drugs and changes after loading.The silicon carrier is a circular nanodisk.Under the scanning electron microscope,the overall diameter of the silicon disk is about 1.5?m,and the surface is loose and porous.The diameter of the hole in the silicon disk is between 30-100nm,and most of the pore size is 50 nm.The pore size is consistent with the size of the drug-loaded microspheres prepared by us.The change after loading the nano drug-loaded microspheres MePEG-PLGA@Boc-GFLG-PTX can also be observed by scanning electron microscopy,which proves that the drug loading is successful.Subsequently,the loading rate of different concentrations of MePEG-PLGA@Boc-GFLG-PTX in the silicon carrier was measured by HPLC method,and the optimal loading concentration was selected.5.Study on drug release,carrier degradation and antitumor effectsThe release of the drug delivery system was studied in PBS and fetal bovine serum at pH 7.2.The in vitro drug release profile was plotted.The degradation of silicon in the blood was simulated in fetal bovine serum,and its degradation was observed by scanning electron microscopy.The killing effect of Si/MePEG-PLGA@Boc-GFLG-PTX on A549 cells at 24 hours and 48 hours was examined by MTT method,and the cytotoxicity of the block copolymer MePEG-PLGA and the silicon carrier was also examined.