N-乙烯基-2-吡咯烷酮-丙烯酸共聚物/聚乙二醇半互穿网络水凝胶的合成及其药物缓释性能

N-乙烯基-吡咯烷酮;释药;N-乙烯基-2-吡咯烷酮-丙烯酸共聚物/聚乙二醇半互穿网络水凝胶的合成及其药物缓释性能     

Characterization of UV-curable Poly(ethylene glycol)Diacrylate Based Hydrogels

Poly(ethylene glycol) diacrylate/polyvinyl alcohol(PEGDA/PVA) hydrogels were prepared from PEGDA and PVA as precurors by means of single UV radiation(UV ra.), UV radiation followed by high energy electron beam irradiation(Irra.), UV radiation followed by freeze-thawing(FT) or UV ra. and Irra. followed by FT, respectively. 2-Hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone(Irgacure 2959) was used as a photoinitiator. The effects of the various methods on the swelling and mechanical properties of the hydrogels were investigated. The results show that hydrogels made by UV ra. plus high energy electron beam irradiation followed by FT showed a higher crosslinking density and a larger tensile strength than those made by the other methods.     

N-异丙基丙烯酰胺/N-乙烯基吡咯烷酮水凝胶的研究

研究了用Ｎ,Ｎ－亚甲基双丙烯酰胺作交联剂,Ｎ－异丙基丙烯酰胺／Ｎ－乙烯基吡咯烷酮共聚物水凝胶的合成与性能。结果表明,ＮＶＰ能显著延长共聚体系的凝胶化时间,但对共聚物的体积相变温度影响并不十分显著。当Ｎ－乙烯基吡咯烷酮的配料摩尔比（Ｎ－乙烯基吡咯烷酮／Ｎ－异丙基丙烯酰胺＋Ｎ－乙烯基吡咯烷酮）＝０．０１时,水凝胶呈现最大Ｔｃ和平衡溶胀胀比。当温度低于Ｔｃ时共的在水中的平衡溶胀比与Ｎ－异丙基丙烯酰胺和Ｎ－乙烯基吡咯烷酮的配料比有关;Ｎ－乙烯基吡咯烷酮配料摩匀比〈０．０１,平衡溶胀比随Ｎ－乙烯基吡咯烷酮配料摩尔比的增加而增加;Ｎ－乙烯基吡咯烷桐配料摩尔比〉０．０１,平衡溶胀比随Ｎ－乙烯基吡咯烷酮配料摩尔浓度的增加而降低。同Ｎ－并异丙烯酰胺均聚物水凝胶相比,共聚物水凝胶具有较好的温敏响应性。ＤＳＣ和ＴＧＡ研究表明,Ｎ－乙     

Novel Hydrogels for Rhythmic Pulsatile Drug Delivery

Summary: We are investigating an autonomous glucose-driven hydrogel/enzyme-based device prototype for rhythmic, pulsed delivery of gonadotropin releasing hormone (GnRH). The device employs a pH-sensitive hydrogel membrane in conjunction with the enzyme glucose oxidase. This system delivers GnRH in rhythmic pulses when exposed to a constant level of glucose. These pulses result from autonomous pH oscillations inside the device that are created by an unstable nonlinear feedback between hydrogel permeability to glucose and production of acid by glucose oxidase. Previous versions of this prototype utilized p(N-isopropylacrylamide-co-methylacrylic acid) p(NIPA-co-MAA) hydrogels, with 10 mol% MAA incorporated. With this membrane, which undergoes a volume transition (VT) near pH 5, pH oscillations centered around pH 5 are observed. This range is too low to sustain oscillations in physiologically buffered media. To shift the operating pH of oscillations closer to physiologic pH, we have sought ways to increase the pH of the volume transition. In this study we show that increasing the side chain length of the α-alkylacrylic acid (RAA) comonomer enhances the overall hydrophobicity of the copolymer, and shifts the VT pH closer to physiological pH values. We also demonstrate the ability of such membranes to affect an alkaline shift in the range of oscillations in the prototype oscillator device.     

环状RGDs修饰的分子刷型共聚物在成像及药物运输中的应用

以具有丰富接枝侧链的阴离子型共轭聚合物分子刷PFPANa为材料,通过简单的一步修饰法在聚合物的部分接枝侧链上引入靶向配体分子c(RGDyK),并利用分子刷侧链上未修饰配体分子的羧基负离子与抗癌药物DOX静电结合,制备了基于分子刷型共轭聚合物的靶向细胞成像和载药系统.研究结果表明载药系统对DOX药物的载药量可达13.3 wt%,体外细胞实验研究结果表明该载药系统可实现对肿瘤细胞的靶向选择性成像,并显著促进了肿瘤细胞对DOX药物的摄取,具有良好的抗肿瘤细胞生长效果,显著提高了药物运输效率.     

聚L-谷氨酸可注射水凝胶的制备及性能

通过活化改性聚L-谷氨酸（PLGA）制备酰肼化PLGA（PLGA-ADH）和3-氨基-1,2-丙二醇改性的PLGA（PLGA-OH）,PLGA-OH经高碘酸钠氧化制得醛基化PLGA（PLGA-CHO）,以PLGA-ADH和PLGA-CHO为前驱体,通过席夫碱交联反应构建了PLGA可注射水凝胶.研究了酰肼化和醛基化改性前后PLGA的结构变化,考察了固含量对水凝胶成胶时间、溶胀行为、机械性能、体外降解性能、药物释放行为及微观形貌等的影响,并进行了初步的细胞培养实验及裸鼠皮下注射成胶实验.结果表明,该PLGA可注射水凝胶在组织工程领域具有良好的应用前景.     

Synthesis and Characterization of Poly(ethylene glycol) Dimethacrylate Hydrogels

Facile synthesis and detailed characterization of photo-polymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and their hydrogels are described. Combined analyses of ¹H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). A systematic investigation into the structure and mechanical properties of PEGDM hydrogels was performed to characterize the relationships between the network structure and gel properties. Small-angle neutron scattering was used to characterize the structural features of hydrogels with respect to their semidilute solution precursors. A well-defined structural length scale (correlation length) manifested as a maximum in the scattering intensity was observed for hydrogels derived from high molecular mass PEGDMs and/or high oligomer mass fractions. Hydrogels derived from lower molecular mass PEGDMs and/or low oligomer mass fractions exhibited multiple correlation lengths suggesting the formation of inhomogeneous gel structures. The shear moduli, determined from uniaxial compression measurement, showed that the gel structures correlate well with the gel mechanical properties.     

纤维素纳米纤维接枝聚(N-异丙基丙烯酰胺)水凝胶的制备与表征

将具有温度响应的聚N-异丙基丙烯酰胺(PNIPAm)接枝到电纺纤维素纳米纤维膜上,制备温度响应型纤维素接枝聚N-异丙基丙烯酰胺(PNIPAm-g-Cell)纳米纤维水凝胶。 研究接枝单体(N)与纤维素(c)的质量比、反应温度、反应时间和引发剂浓度对产物接枝率、溶胀性和形貌的影响。 结果表明,最佳聚合反应条件为m(N):m(c)=15:1、反应温度40 ℃、反应时间3 h、引发剂浓度为10 mmol/L,得到PNIPAm-g-Cell接枝率和溶胀率分别为35%和31%。 与PNIPAm相比,PNIPAm-g-Cell水凝胶的低临界相转变温度(LCST)显著升高,说明亲水性纤维素的引入改变了体系的亲疏水平衡。 去溶胀动力学测试表明,0.5 min内接枝率为25%和35%的水凝胶保水率分别降低至93%和61%。 说明接枝率越高PNIPAm-g-Cell水凝胶对温度的响应速度越快,对温度越敏感。     

两亲嵌段聚合物载药胶束研究进展

在临床应用中,抗肿瘤药物的憎水性将严重影响疗效并造成一系列的副作用,因此,这些憎水性药物的增溶方法一直是研究的热点,其中,两亲嵌段聚合物载药胶束体系是目前最有效的方法之一,该方法通过将憎水性药物包裹在具有"核-壳"结构的纳米微球中以实现增溶目的。本文总结了目前用于载药胶束的两亲嵌段聚合物的材料及胶束的制备方法,介绍了超临界二氧化碳在此类药物胶束制备中的最新应用和该领域目前最为热门的研究方向——对肿瘤细胞具有靶向释药功能胶束的研究进展。     

Synthesis and Drug Release Properties of Thermosensitive Poly(N-vinylacetamide-co-vinylacetate) Hydrogels

Thermosensitive poly[N-vinylacetamide-co-vinylacetate][P(NVA-co-VAc)] hydrogels were prepared via free radical copolymerization from hydrophilic NVA and hydrophobic VAc in the presence of butylenes-bis (N-vinylacetamide)(Bis-NVA) as crosslinker. Scanning electron microscopy(SEM) images reveal that the as-prepared hydrogels were of three-dimensional network with irregular cave structure. The prepared hydrogels with more NVA in the feed swelled faster and the swelling ratio of the hydrogels gradually decrease...     

温度/pH敏感性接枝共聚物水凝胶P(DMAEMA-g-NIPAM)的 合成及性质研究

利用大分子单体技术, 采用自由基溶液聚合合成了温度/pH敏感性聚甲基丙烯酸-N,N-二甲氨基乙酯接枝聚N-异丙基丙烯酰胺[P(DMAEMA-g-NIPAM)]水凝胶. 用红外光谱及扫描电镜对凝胶的组成及形貌进行了表征. 凝胶的去溶胀和溶胀动力学研究表明, 所合成的凝胶具有温度和pH敏感性. 与传统的聚丙烯酸系水凝胶相比, P(DMAEMA-g- NIPAM)具有相反的pH敏感性; P(DMAEMA-g-NIPAM)凝胶在55 ℃时具有较快的去溶胀速率, 随着凝胶中接枝链PNIPAM量的增加, 凝胶的去溶胀速率加快.     

Preparation and Characterization of Attractive Poly(amino acid)Hydrogels Based on 2-Ureido-4[1H]-pyrimidinone

Self-healing hydrogels with the shear-thinning property are novel injectable materials and are superior to traditional injectable hydrogels.The self-healing hydrogels based on 2-ureido-4[1 H]-pyrimidinone(UPy)have recently received extensive attention due to their dynamic reversibility of UPy dimerization.However,generally,UPy-based self-healing hydrogels exhibit poor stability,cannot degrade in vivo and can hardly be excreted from the body,which considerably limit their bio-application.Here,using poly(l-glutamic acid)(PLGA)as biodegradable matrix,branchingα-hydroxy-ω-amino poly(ethylene oxide)(HAPEO)as bridging molecule to introduce UPy,and ethyl acrylate polyethylene glycol(MAPEG)to introduce double bond,the hydrogel precursors(PMHU)are prepared.A library of the self-healing hydrogels has been achieved with well self-healable and shear-thinning properties.With the increase of MAPEG grafting ratio,the storage modulus of the self-healing hydrogels decreases.The self-healing hydrogels are stable in solution only for 6 h,hard to meet the requirements of tissue regeneration.Consequently,ultraviolet(UV)photo-crosslinking is involved to obtain the dual crosslinking hydrogels with enhanced mechanical properties and stability.When MAPEG grafting ratio is 35.5%,the dual crosslinking hydrogels can maintain the shape in phosphate-buffered saline solution(PBS)for at least 8 days.Loading with adipose-derived stem cell spheroids,the self-healing hydrogels are injected and self-heal to a whole,and then they are crosslinked in situ via UV-irradiation,obtaining the dual crosslinking hydrogels/cell spheroids complex with cell viability of 86.7%±6.0%,which demonstrates excellent injectability,subcutaneous gelatinization,and biocompatibility of hydrogels as cell carriers.The novel PMHU hydrogels crosslinked by quadruple hydrogen bonding and then dual photo-crosslinking of double bond are expected to be applied for minimal invasive surgery or therapies in tissue engineering.     

Synthesis,Characterization, and Application of Poly[Substituted Methylene]S

Radical polymerization of fumaric acid derivatives, such as dialkyl fumarates, gave polymers consisting of a less-or nonflexible substituted polymethylene structure. The yield and molecular weight of the polymers produced increased as the bulkiness of the ester substituents increased. For example, when di-t-butyl fumarate was polymerized in bulk with azocyclohexanecarbonitrile (20 mmol/L) at 80°C for 6 h, polymer with M _n of more than 100 000 was produced in more than 80% yield. The polymers obtained were colorless powders and did not melt before degradation at ～250°C, but they were soluble in such organic solvents as benzene, carbon tetrachloride, tetrahydrofuran, and dioxane. A transparent brittle film or fiber was obtained from toluene solution. Some properties and possibilities for application of these polymers are described and discussed.     

Synthesis and Characterization of Doxorubicin-Loaded Poly(Lactide-co-glycolide) Nanoparticles as a Sustained-Release Anticancer Drug Delivery System

The objective of the present study was to prepare a polymeric drug delivery system with no burst effect. To attain this goal, doxorubicin (Dox) as an effective anticancer drug was loaded into poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) to improve the drug performance and also maximize the release period. After the synthesis process, the freshly made PLGA NPs with two different lactide-to-glycolide ratios (75:25 and 50:50) were evaluated physically and chemically. To determine the encapsulation efficiency, a centrifugation method was applied. Also, the drug loading effect on particle size, polydispersity index, and zeta potential was examined. The results indicated that the NPs had nearly the same diameters around 360?nm, and the entrapment efficiencies for 75:25 PLGA and 50:50 PLGA were reported around 39 and 48?%, respectively. A slight increase in all parameters was observed due to the increase of the drug loading content. The primary release was 7.91?% (w/w) and 14.70?% (w/w) for 75:25 and 50:50 drug-loaded NPs, respectively; no burst effect was observed. After 20?days, the drug release was around 70.98 and 62.22?% of the total entrapped drug for 75:25 and 50:50 drug-loaded NPs, respectively. Finally, it was found that Dox was an appropriate anticancer agent with good capability to be encapsulated in polymeric NPs and could be released from the carriers with no burst effect and favor rate.     

配合物[2-NaPhthMePyNH_2]_2[Ni(mnt)_2]的合成及表征

合成了马来二氰基二硫烯镍(Ⅱ)配合物,[2-Na Phth Me Py NH2]2[Ni(mnt)2]([2-Na Phth Me Py NH2]+为1-(2'-萘苄基)-2-氨基吡啶鎓离子),并用元素分析,UV,IR,单晶X-射线衍射表征了其组成和结构。结果表明,配合物系单斜晶系,空间群P21/c,a=13.335(2),b=7.9458(12),c=17.480(3),α=90°,β=97.646(2)°,γ=90°,V=1835.7(5),Z=2。     

Dendrimer-based Hydrogels with Controlled Drug Delivery Property for Tissue Adhesion

In recent years,the hydrogel-based tissue adhesives have been extensively investigated for their excellent biocompatibility and the ability to be administered directly within the adherent tissue.To meet the requirement for more controllable release in various physiological settings,the components of hydrogel adhesive should be more precisely tailored.In this work,the POSS-ace-PEG hydrogel adhesive was fabricated with the polyacetal dendrimer G1'-[NH3Cl]16 and poly(ethylene glycol) succinimidyl carbonate (PEG-SC) due to the regular peripheral amino structure of G1'-[NH3Cl]16.Rheological and adhesion tests demonstrated that the hydrogel adhesive had good mechanical and adhesive properties,which could effectively adhere to the pigskin and severed nerves.Moreover,the tissue adhesive exhibited good stability under neutral conditions and the rapid degradation under acidic conditions,allowing for the release of doxycycline hydrochloride (DOX) drug in response to pH.Together,these results suggested that the POSS-ace-PEG adhesive had the potential to provide an alternative to tissue adhesives for applications in pathological environments (inflammation,tumors,etc.).     

Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine

A novel, pH-responsive supramolecular graft copolymeric micelle, composed of dextran and poly (oleic acid), has been synthesized through reversible addition fragmentation chain transfer polymerization with controlled M_n and narrow polydispersity. The structural properties of the copolymer have been studied using FTIR and ¹H NMR spectral analyses. Critical micelle concentration (CMC) has been determined fluorometrically and conductometrically. The copolymer shows pH responsive micellar stability, which has been confirmed using DLS study. Dextran-g-OA copolymer demonstrates spherical morphology at CMC, while rod-like assembly has been evidenced beyond CMC that is probably because of the structural alteration of copolymeric chains at higher copolymer concentration. Dextran-g-OA is noncytotoxic toward MG-63 cells. As the self-assemble nature of copolymer micelle promotes the oral administration of hydrophobic drugs, nifedipine (NFD, a hydrophobic drug) has been used as model drug that has been encapsulated substantially into the core of the micelle. The copolymer releases the loaded NFD at a much slower rate in simulated gastric fluid (pH 1.2) and relatively faster in simulated intestinal fluid (pH 7.4) with a cumulative release of ~95% within 24 h, suggesting an ideal candidate as nifedipine carrier. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2354–2363