Synthesis,Characterization, and Viscoelastic Behavior of Thermothickening Poly (N-Isopropylacrylamide-Methacrylicacide-Vinylpyrrolidone) Nanogels as an Injectable Biocompatible Drug Carrier

In the present work, the preparation of dual thermo-/pH-responsive nanogels composed poly (NIPAAm-MAA-VP) was investigated as an injectable carrier in which doxorubicin hydrochloride (DOX) was opted as an anticancer agent. The SEM photomicrographs showed that copolymer was almost spherical in shape with the mean diameter below 30 nm. Using dynamic oscillatory the gel-like behavior was observed at 37°C for the crosslinked polymer. Biocompatibility of the synthesized nanoparticles and superior antitumor activity of DOX-loaded nanoparticles were proved by in vitro cytotoxicity assay. The system is expected to be valuable for the delivery of chemotherapeutic agents in the treatment of solid tumors.     

自组装法制备CMCS/PEG纳米粒子及其pH值响应性研究

以壳聚糖(CS)为原料与氯乙酸反应制备羧甲基壳聚糖(CMCS),再将聚乙二醇(PEG)和CMCS以不同的质量比溶解在不同pH值的溶液中,通过氢键相互作用自组装形成CMCS/PEG纳米粒子,并研究其粒径大小与二者配比和溶液pH值之间的关系。结果表明,不同配比下的粒子粒径均随pH值的增大先增大后减小;当pH5时,在相同pH值溶液中,随着PEG比例的增加,粒子的粒径先减小后增大,在pH=1.22、PEG∶CMCS=4∶1时粒径最小,约为160nm;当pH≥5时,在相同pH值溶液中,粒径随PEG用量的增加而增大;通过自组装法制备的CMCS/PEG纳米粒子粒径大小具有pH值响应性。     

Dual-responsive polymer–drug nanoparticles for drug delivery

A well-defined, dual temperature- and pH-responsive drug carrier was synthesized through the radical copolymerization of methacrylic acid, N-isopropylacrylamide, and an N-(methacryloyl)glycylglycine 4-nitrophenyl ester. When the anticancer agent gemcitabine or antibiotic sulfamethoxazole was conjugated with a polymer and heated beyond its low critical solution temperature (40 °C), a dual temperature- and pH-induced phase transition was observed. This temperature was considered ideal for activating drug aggregation under hyperthermic and acidic conditions. The structure and properties of polymer drugs were investigated using nuclear magnetic resonance, Fourier transform infrared spectrometry, ultraviolet–visible absorption, transmission electron microscopy, and gel permeation chromatography. At a critical micelle concentration of 1 mg/mL, both polymer drugs formed micellar structures with diameters ranging from 50 nm to 150 nm, based on TEM image. These micelles exhibited higher pharmacological efficacy than the free drug alone did, and the cytotoxicity at the target site was substantially enhanced compared with that of the polymer–drug conjugate formed under normal physiological conditions.     

Functional copolymer coatings on electrospun fibers via photo-initiated chemical vapor deposition

With the increasing use of implantable patches in biomedical applications, the significance of surface modification techniques in improving biocompatibility, enhancing adhesion, and regulating drug release has grown. A significant challenge that these methods must address is ensuring that the process does not harm the delicate fibers or therapeutic agents they contain. Here, we report surface functionalization of implantable, curcumin loaded Polycaprolactone (PCL) patches with pH-responsive poly(2-hydroxyethyl methacrylate-co-4-vinylpyridine), p(HEMA-co-4VP) polymer thin film. The polymer was coated on the patch surface via photo-initiated chemical vapor deposition (piCVD) where the polymerization was initiated by the UV degradation of the initiator tert-butyl peroxide (TBPO) and the monomer HEMA. Additionally, the piCVD method was utilized to crosslink the HEMA without the use of additional crosslinkers. The pH-responsiveness of the coating was achieved by incorporating 4VP into the copolymer structure. The effect of the coating was demonstrated through degradation and drug release studies. The presence of the polymer coating decelerated the fiber degradation and the pH-dependent swelling of the coating allowed for the control of drug release rates from the patches. The innovative use of piCVD as a coating method provides a platform for advancing tailored surface modifications in various biomedical applications.     

双重响应N-乙烯基己内酰胺、甲基丙烯酸共聚微凝胶的研究

以N-乙烯基己内酰胺、甲基丙烯酸为单体,N,N-亚甲基双丙烯酰胺为交联剂,过硫酸钾为引发剂,利用沉淀聚合法合成了一系列具有pH和温度双重响应性的微凝胶。利用红外光谱技术对微凝胶进行了结构表征,结果表明,制备的微凝胶是两种单体的共聚物;分别利用光散射技术和浊度法考察了微凝胶的温度响应性和pH响应性,结果表明这些微凝胶具有良好的温度和pH响应性。     

Self-assembly of pH-responsive and fluorescent comb-like amphiphilic copolymers in aqueous media

“Comb-like” graft copolymers, consisting of a poly((N-vinylcarbazole)-co-(4-vinylbenzyl chloride)) (P(NVK-co-VBC)) copolymer backbone from free radical polymerization and poly(((2-dimethylamino)ethyl methacrylate)-co-(tert-butyl acrylate)) (P(DMAEMA-co-tBA)) side chains from atom transfer radical polymerization (ATRP), were hydrolyzed to produce the acrylic acid (AAc)-containing “comb-like” graft copolymers of P(NVK-co-VBC)-comb-P(DMAEMA-co-AAc). The amphiphilic copolymers possess a fluorescent hydrophobic P(NVK-co-VBC) backbone and pH-sensitive hydrophilic P(DMAEMA-co-AAc) side chains. Arising from acid-base interaction of the hydrophilic side chains, the copolymers can self-assemble into pH-responsive fluorescent and multi-walled hollow vesicles of well-defined morphology in aqueous media. The size and layered wall thickness of the vesicles are also dependent on the length of the copolymer side chains, while the number of wall layers is dependent on the concentration of the vesicles in the aqueous media. In comparison, a N-isopropylacrylamide (NIPAAm)-containing comb-like amphiphilic copolymer (P(NVK-co-VBC)-comb-P(NIPAAm-co-DMAEMA)) of similar structure, albeit with non-interacting hydropholic side chains, self-assembles only into temperature and pH-responsive single-shelled hollow nanoparticles in aqueous media.     

pH-responsive swelling behavior of poly(vinyl alcohol)/poly(acrylic acid) bi-component fibrous hydrogel membranes

The pH-responsive dimensional expansion and mass uptake of bi-component hydrogels in the form of fibrous membranes and films were reported. Fibrous membranes and monolithic films were prepared from aqueous mixture of poly(vinyl alcohol) and poly(acrylic acid) at 3.5 COOH/OH molar composition via electrospinning and solution cast, respectively, then cross-linked by heat-induced esterification. Both forms of hydrogels exhibited increasing swelling with increasing pH. For hydrogel fibrous membranes, planar expansion was immediate without the time lag observed on the films, and equilibrium thickness expansion and mass uptake took far longer than planar expansion. The dimensional expansion in the thickness direction was much higher than that in the planar directions for the fibrous membranes, while they were comparable for monolithic films. The peculiar asymmetric dimensional expansion of fibrous membrane is explicable with the asymmetric distribution of the fibers on the planar and thickness directions, which is formed during layer-by-layer collection process of electrospinning. The fibrous membranes distinguished themselves as being far stronger and faster in re-absorption in the swollen state than the cast-films.     

碳量子点掺杂的蠕虫状胶束

以富勒烯生产过程中的副产物炭灰为原料,利用酸回流法制备了表面含有羧基的碳量子点(CQDs)。将所制备的CQDs代替传统有机酸,发现其与十四烷基二甲基氧化胺(C_(14)DMAO)在水溶液中能形成蠕虫状胶束。考察了CQDs质量浓度、pH等对蠕虫状胶束流变性质的影响。结果表明,CQDs质量浓度的增加和溶液pH值的降低均有利于蠕虫状胶束的形成。利用低温透射电镜可以原位地观察到蠕虫状胶束和CQDs的存在。CQDs外围-COOH解离出的H~+可以使C_(14)DMAO质子化为C_(14)DMAOH~+,而C_(14)DMAOH~+与C_(14)DMAO之间形成的氢键是蠕虫状胶束形成的主要驱动力。以上结果表明,CQDs可以有效地诱导C_(14)DMAO形成蠕虫状胶束。     

超临界CO_2中pH-响应型壳聚糖膜的制备及性能

以壳聚糖为膜基材,制备壳聚糖基多孔膜,并在超临界二氧化碳中,以丙烯酸(AA)和4-乙烯基吡啶(4-VP)为接枝共聚单体,对壳聚糖多孔膜进行接枝,制备了p H-响应型壳聚糖多孔膜。采用傅里叶变换红外光谱和X射线衍射等对接枝膜的结构进行表征,考察了2种接枝单体的摩尔比及反应压力对壳聚糖膜接枝率的影响,以及接枝膜对蛋白质的吸附。红外结果表明聚丙烯酸与聚4-乙烯基吡啶均接枝到壳聚糖膜上。当AA/4-VP单体摩尔比由3∶1增加至6∶1时,接枝率由7.12%逐渐增大至13.36%,此后呈下降趋势。且随着反应压力的提高,壳聚糖膜接枝率先增长后降低,当反应压力在19 MPa时,得到较高的接枝率(13.36%)。当溶液p H=2~10时,壳聚糖接枝膜的水通量随着p H值的增大而降低。蛋白质吸附实验显示,在p H为4.8时接枝膜获得最大比表面积吸附量5.76 mg/cm2。     

A novel intracellular pH-responsive formulation for FTY720 based on PEGylated graphene oxide nano-sheets

Objective: This study was performed to investigate a novel pH-responsive nanocarrier based on modified nano graphene oxide (nGO) to promote the acid-triggered intracellular release of a poorly soluble drug, FTY720.

Methods: To synthesize a drug conjugated to modified nGO, first the polyethylene glycol (PEG) was conjugated to nGO, then the produced PEG-nGO was functionalized with the anticancer drug, FTY720, through amide bonding. It was characterized by the scanning electron microscopy (SEM), the atomic force microscopy (AFM), the Fourier transform infrared (FTIR) spectroscopy and the UV–vis spectroscopy. In vitro drug release of the FTY720-conjugated PEG-nGO was evaluated at pH 7.4 and 4.6 PBS at 37?°C. Furthermore, the antineoplastic action of unloaded and drug-loaded carrier against the human breast adenocarcinoma cell line MCF7 was explored using MTT and BrdU assays.

Results: Characterization methods indicated successful drug deposition on the surface of nGO. In vitro, drug release results revealed a significantly faster release of FTY720 from PEG-nGO at acidic pH, compared with physiological pH. The proliferation assays proved that the unloaded nGO had no significant cytotoxicity against MCF7 cells, while free FTY720- and FTY720-loaded PEG-nGO had an approximately equal cytotoxic effect on the MCF7 cells. It was found that the extended release characteristic of FTY720 was well fitted to Korsmeyer–Peppas model and the release profile of FTY720 from PEG-nGO is diffusion controlled.

Conclusion: PEGylated GO can act as a pH-responsive drug carrier to improve the efficacy of anticancer drug delivery.