Preparation Of Nanogels Loading Antitumor Drugs In Situ By 532 Nm Laser Induced Polymerization

Nanogels have very extensive application in the biomedical field.Nanogel is a promising drug carrier due to its three-dimensional network structure,good biocompatibility,large specific surface area and excellent drug performance.Currently,there are many methods to prepare drug-loaded nanogels,but facile,efficient and environmentally friendly preparation method is still deficient.Compared with the large-area exposure of traditional photopolymerization,laser induced polymerization can control the polymerization area more precisely.In this paper,532 nm laser induced polymerization was used to prepare nanogel loaded with anti-tumor drugs in situ to improve the therapeutic effect of anti-tumor drugs.Detailed contents are as follows:Preparation and property regulation of nanogel by 532 nm laser induced polymerization.Nanogels were prepared by 532 nm photopolymerization with polyethylene glycol diacrylate(PEGDA)as the polymerization monomer,eosin Y(EY)as photosensitizer and triethanolamine(TEOA)as the co-initiator.The polymerization parameters including laser power,illumination time,monomer concentration,stirring speed and initiator concentration were optimized.The effects of TEOA on the photopolymerization process at 532 nm and the properties of nanogels were systematically studied by means of UV-vis,FT-IR,~1H NMR,dynamic light scattering,scanning electron microscopy,atomic force microscopy and differential scanning calorimetry.Nanogels loaded with 5-fluorouracil(5-Fu)in situ were prepared by combining thiol-ene click reaction and 532 nm laser induced polymerization and its controlled release was investigated.Based on the preparation of nanogels by laser induced polymerization at 532 nm.The mercaptosuccinic acid,which can easily react with polymerized monomers in water,was introduced to improve the cross-linking degree of nanogels and a lot of hydrogen bond donors were introduced.5-Fu was model drug,mercaptosuccinic acid was thiol reagent,PEGDA was crosslinking monomer and EY/TEOA was co-initiating system.Nanogels loaded with 5-Fu(NG-S)in situ were prepared by combining thiol-ene click reaction and 532 nm laser induced polymerization.The morphology,double bond residue ratio,sulfhydryl modification degree,swelling property,physicochemical stability,and drug loading content of NG-S were characterized.The size of NG-S was about 180 nm,and the polydispersity index(PDI)was no more than 0.3.The drug loading content and swelling rate characteristics of drug-loaded nanogels can be adjusted by changing the proportion of reactive monomers and the initial dosage of administration.At the same time,the release behavior of drugs in vitro was investigated and the release kinetics was elucidated.Nanogels loaded with curcumin(NG-C)in situ were prepared by microemulsion photopolymerization to enhance the antitumor efficacy of the drug.The morphology,zeta potential,stability,chemical structure,drug-polymer interaction,drug loading content and drug release characteristics of NG-C were studied.The size of NG-C was about 150 nm,and the PDI was around 0.1.The drug loading content of NG-C was 8.96±1.16 wt%.The cumulative release amount of NG-C at p H 7.4,6.8 and 5.0 within 90h was 25%,34%and 55%in buffer solution,respectively.Cellular uptake and cytotoxicity of NG-C in tumor cells(He La and Hep G2)and the distribution of nanogels in vivo were investigated.Finally,in vivo antitumor properties were studied by intravenous injection of NG-C in nude Hep G2 tumor bearing mice.NG-C can inhibit tumor growth significantly in tumor bearing nude mice,with a tumor inhibition rate of about 56%,and showed good biocompatibility.Nanogels co-loaded with paclitaxel and curcumin as model drugs in situ were prepared by microemulsion photopolymerization for synergistic inhibition of breast tumors.EY/TEOA was co-initiating system,PEGMA was monomer,PEGDA was crosslinking agent,methacrylic acid(MAA)was acidity regulator and Tween 80 was emulsifier.Paclitaxel and curcumin were added into the reaction system,and microemulsions were prepared by phase transfer emulsification method.Then drug-loaded nanogel(NG-PC)was obtained by laser induced polymerization in situ.The size of NG-PC was 180 nm,and the PDI was less than 0.2.NG-PC showed controlled release of paclitaxel and curcumin within 90 h,and had obvious killing effect on 4T1and MCF-7 cells.The in vivo anti-tumor evaluation of 4T1 tumor-bearing mice showed that the inhibitory effects of NG-PC on tumor growth,tumor necrosis,cell apoptosis and proliferation were significantly higher than those of single drug and mix free drugs.This study provides a facile method for preparing nano-drug delivery platform with good drug carrying capacity and synergistic anti-tumor effect.