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APPLIED SURFACE SCIENCE · 2012 · IF 2.103

Synthesis and characterization of asymmetric polymer/inorganic nanocomposites with pH/temperature sensitivity

Xinjie Zhang,Chunmei Gao,Mingzhu Liu,Yinjuan Huang,Xiyong Yu,Enyong Ding

An easy, comprehensive and inexpensive method is demonstrated to produce asymmetric polymer/inorganic nanocomposites in a large quantity. With the aid of Pickering emulsion, unmodified particles aggregate on the surface of emulsion droplets and are fixed in place when the wax solidifies. The exposed surfaces of immobilized SiO 2 particles are modified chemically by 2-(dimethylamino) ethylmethacrylate (DMAEMA). With the removal of wax, the exposed side of particles can be further modified chemically by N-isopropylacrylamide (NIPAAm). Based on these procedures, dual responsive asymmetric nanocomposite particles are achieved with both pH and temperature sensitivities. Due to their dual-stimuli and asymmetric structure, these particles have potential applications in molecule targeting, drug delivery and as building blocks for the assembly of complex nanostructure.

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MACROMOLECULES · 2012 · IF 5.167

pH-Sensitive Block Copolymer Vesicles with Variable Trigger Points for Drug Delivery

Jianzhong Du,Lang Fan,Qiuming Liu

We have previously reported the preparation of a novel pH-sensitive and biocompatible polymer vesicle in pure water based on the spontaneous self-assembly of a diblock copolymer, PMPC-b-PDPA, where PMPC is poly[2-(methacryloyloxy)ethyl phosphorylcholine] and PDPA is poly[2-(diisopropylamino)ethyl methacrylate] ( J. Am. Chem. Soc. 2005, 127, 17982). Herein, we intend to report the strategy for controlling the pH trigger points of association/dissociation of pH-responsive polymer vesicles for anticancer drug delivery. We introduced a reactive block, poly[2-(dimethylamino)ethyl methacrylate] (PDMA) into the above diblock copolymer to form reactive PMPC-b-PDMA-b-PDPA and PMPC-b-PDPA-b-PDMA triblock copolymers, as well as PMPC-b-P(DMA-stat-DPA) block-statistical copolymer by atom transfer radical polymerization (ATRP) in methanol at room temperature. As a result of different block length of PDPA, the introduction of PDMA chain at different positions, and different initial copolymer concentrations, those block copolymer vesicles showed tunable pH trigger points and various isoelectric points (IEPs) in aqueous solution. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) studies confirmed that the block copolymers with relatively long PDPA block form polymer vesicles by simply tuning the solution pH in pure water. Above pH 6.2, the PDPA block becomes hydrophobic so it forms the vesicle membrane. In all cases, the hydrophilic PMPC chains form the vesicle coronas. The PDMA chains are designed in three different positions. In PMPC-b-PDMA-b-PDPA vesicles, the PDMA chains form the middle shell between the PDPA vesicle membrane and the PMPC vesicle corona. In PMPC-b-PDPA-b-PDMA vesicles, the PDMA can mix with PMPC to serve as mixed coronas. In PMPC-b-P(DMA-stat-DPA) vesicles, the reactive PDMA chains can be incorporated into the vesicle membrane, which provides an effective strategy regarding the immobilization of vesicles by selective quaternization of PDMA with a bifunctional cross-linker, such as 1,2-bis(2-iodoethoxy)ethane (BIEE). The degree of cross-linking can be tuned by varying the molar ratio of PDMA to BIEE, which was further investigated by 1H NMR, DLS, and TEM, suggesting tunable permeability of vesicle membrane. The triblock copolymer vesicles were able to encapsulate anticancer drugs such as DOX, exhibiting obviously retarded release profile at physiological conditions.

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JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY · 2015 · IF 3.512

Dendritic porous SnO2/SiO2@polymer nanospheres for pH-controlled styptic drug release

Na Cao,Xin Xie,Yu Zhang,Yanbao Zhao,Liuqin Cao,Lei Sun

Dendritic porous tin oxide/silica (DTS) nanospheres (NSs) were prepared by emulsion-condensation route. DTS NSs have an average diameter of 80   nm and possess accessible center-radial large pore channels, which endow them high surface area, less drug diffusion resistance and more mass transport. SnO 2 quantum dots (QDs) embedded in silica skeleton can be used to track the drug release behavior. DTS NSs were coated by chitosan/polymethacrylic acid and polymer shell would make them achieve great loading capacity and pH-sensitive release for aminomethylbenzoic acid (AMBA).

CAS / MDL: 919-30-2
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Materials Science & Engineering C-Materials for Biological Applications · 2015 · IF 3.088

Fabrication of SnO2/porous silica/polyethyleneimine nanoparticles for pH-responsive drug delivery

Na Cao,Miao Li,Yanbao Zhao,Li Qiu,Xueyan Zou,Yu Zhang,Lei Sun

To create novel nanocarriers for achieving excellent drug delivery performance, pH-responsive fluorescent porous silica (PS) nanocarriers were developed by encapsulating SnO 2 nanoparticles and coating polyethyleneimine (PEI) layer. SnO 2 /porous silica (SnO 2 /PS) nanoparticles have an average diameter of 80   nm and center-radial large pore channels. The large channels endow them high surface area with a Brunauer–Emmett–Teller (BET) area of 939   m 2   g −   1 . Aspirin was used as test drug to evaluate the releasing behavior of SnO 2 /porous silica/polyethyleneimine (SnO 2 /PS/PEI) nanoparticles. Results indicated that aspirin can be successfully incorporated into the SnO 2 /PS/PEI nanoparticles and the SnO 2 /PS/PEI nanoparticles displayed excellent pH-responsive release. The release rate in pH   7.4 buffer is higher than that in pH   5.5 buffer, which attributed to the PEI structure change in varied pH buffer. In addition, the SnO 2 /PS/PEI nanoparticles presented novel drug-dependent fluorescence, which could be used to trace the drug release.

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Journal of Materials Chemistry B · 2015 ·Vol. 3 ·期 45 ·8884-8891 · IF 4.726

Chitosan-decorated calcium hydroxide microcapsules with pH-triggered release for endodontic applications

Xiaoman Li,Bing Han,Xiaoyan Wang,Xuejun Gao,Fuxin Liang,Xiaozhong Qu,Zhenzhong Yang

The treatment of apical periodontitis (AP) remains challenging because traditional root canal therapy (RCT) outcomes are limited by the complexity of the root canal system, drug toxicity, and host immune factors. It is necessary to develop methods to prepare controlled drug release vehicles with improved biocompatibility for treatment of AP. Herein, calcium hydroxide microcapsules with chitosan and ethylcellulose coated (CS–EC@Ca(OH)2 microcapsules) were prepared and the presence of hydrogen bonding between shell materials was observed by FT-IR. Through release assessment and biological assays, we showed that the microcapsules had enhanced controlled-release performance and biocompatibility. In particular, drug release from the microcapsules was pH-triggered. The cumulative release of drugs in pH 5.0 buffer was 8-fold higher than that in pH 7.0 buffer. Furthermore, the microcapsules exhibited prolonged antibacterial activity against refractory strains of Enterococcus faecalis. Additionally, the CS–EC@Ca(OH)2 microcapsules reduced inflammation and promoted osteogenesis, which could be beneficial for the healing of AP with bone defects. Therefore, CS–EC@Ca(OH)2 microcapsules improve the innate properties of Ca(OH)2 and hold potential for AP treatment.

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RSC Advances · 2015 ·Vol. 5 ·期 13 ·9416-9424 · IF 3.84

Pickering emulsions stabilized by palygorskite particles grafted with pH-responsive polymer brushes

Jia Lu,Wei Zhou,Jing Chen,Yeling Jin,Keisha B. Walters,Shijie Ding

Poly(2-(diethylamino)ethyl methacrylate (PDEAEMA) was grafted from the surface of palygorskite (PAL) particulates via Cu(0) radical polymerization to form PAL–PDEAEMA nanocomposites. The successful grafting was confirmed by Fourier transform infrared (FT-IR), thermal gravimetric analysis (TGA), and elemental analysis (EA). Water (pH 9)/toluene (W/O) Pickering emulsions stabilized by PAL–PDEAEMA particles were prepared. Spherical emulsion droplets with absorbed small PAL–PDEAEMA aggregates on the interface were observed via scanning electron microscopy (SEM), polarizing optical microscopy (POM) and optical microscopy (OM). The size of the emulsion droplets was decreased with the increase of PAL–PDEAEMA particle concentrations, and reached a limited value at 2 wt%. By changing the pH of water (pH < 3), O/W Pickering emulsions were formed by the same PAL–PDEAEMA particles. Moreover, W/O emulsion–de-emulsion–O/W emulsion transitions can be realized simply by adding HCl/NaOH, which can last at least 7 successive cycles. Therefore, a reversible Pickering emulsion system switched by pH can result on the basis of PAL–PDEAEMA particles.

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RSC Advances · 2014 ·Vol. 4 ·期 103 ·58982-58989 · IF 3.708

pH-Responsive supramolecular hydrogels for codelivery of hydrophobic and hydrophilic anticancer drugs

Jing Yu,Wei Ha,Juan Chen,Yan-ping Shi

Codelivery of multiple drugs with one kind of drug carrier provides a promising strategy to suppress the drug resistance and achieve the enhanced therapeutic effect in cancer treatment. In this work, we successfully developed multifunctional supramolecular hydrogels based on in situ host–guest inclusion between polymer-drug conjugates and α-cyclodextrin to codeliver hydrophobic and hydrophilic anticancer drugs with pH-trigged release properties. Taking advantage of the strong hydrophobicity of 4β-aminopodophyllotoxin (NPOD), a derivative of podophyllotoxin (POD), the NPOD molecule was conjugated to low-molecular-weight methoxypoly (ethylene glycol) (mPEG) chain via a pH-responsive imine bond, forming an amphiphilic polymer-drug conjugates (NPOD-PEG). After adding α-cyclodextrin (α-CD) into the NPOD-PEG solutions, the stable supramolecular hydrogels were formed based on a combination of the partial inclusion complexation between one end of the mPEG blocks and α-CD and the hydrophobic aggregation of NPOD groups. The formed hydrogels could further efficiently load another hydrophilic anticancer drug doxorubicin (DOX) for combination therapy purposes. The hydrogel demonstrated unique gel–sol transition properties and pH-dependent dual drug release behavior due to the hydrolysis of imine bond at acidic environments. Furthermore, the cytotoxicity results suggested that the DOX loaded NPOD-PEG/α-CD hydrogels showed an enhanced cytotoxicity in cancer cells in comparison with single modality treatment and the resulting hydrogels are characterized by producing an additive cytotoxicity to cancer cells. In fact, the codelivery of two anticancer drugs with different physicochemical properties and anticancer mechanisms was a key to opening the door to their controlled drug delivery and enhanced anticancer effect. Therefore, DOX loaded NPOD-PEG/α-CD hydrogels as pH-trigged drug codelivery systems might have important potential for combination cancer chemotherapy.

CAS / MDL: 10016-20-3 1122-58-3
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JOURNAL OF APPLIED POLYMER SCIENCE · 2014 ·Vol. 132 ·期 9 · IF 1.64

pH-sensitive keratin-based polymer hydrogel and its controllable drug-release behavior

Juhua Guo,Sujuan Pan,Xiaochun Yin,Yu-Feng He,Tao Li,Rong-Min Wang

Using feather keratin as biocompatible and inexpensive natural biopolymer and methacrylic acid as a functional monomer, we prepared a pH-sensitive feather-keratin-based polymer hydrogel (FKPGel) with grafted copolymerization. The obtained FKPGel was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. The swelling behavior and pH sensitivity of the FKPGel were investigated. When the small molecule (rhodamine B) and macromolecule (bovine serum albumin) were used as model drug molecules, the FKPGel exhibited controllable release behavior in vitro, and the hydrogels had pH sensitivity. For a small molecular drug, the cumulative release rate was 97% in 24 h at pH 8.4. For macromolecular drug, the cumulative release rate reached 89% at pH 7.4. Its release behavior could be controlled by the pH value. In summary, a simple method was found to reuse disused feathers. It is a kind of pH-sensitive hydrogels to be applied in drug-delivery systems. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 41572.

CAS / MDL: 9048-46-8
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2015 · IF 4.152

A pH- and thermo-responsive poly(amino acid)-based drug delivery system

Na Liu,Bingqiang Li,Chu Gong,Yuan Liu,Yanming Wang,Guolin Wu

A pH- and thermo-responsive poly(amino acid)-based amphiphilic copolymer was developed, functioning as a tumour targeting drug delivery system with good biocompatibility and biodegradability. To provide multi-stimuli sensitivity characteristics to the poly(amino acid)s, the polyaspartamide scaffold has been functionalized with N , N -diisopropylamide groups via aminolysis reaction of polysuccinimide. PEG chains have also been chemically grafted to the poly(amino acid) backbone through acid-labile hydrazone linkages, providing a removable shield for the poly(amino acid) based nanoparticles. Furthermore, doxorubicin was chemically linked to the copolymer chain via hydrazone bonds, acting as the hydrophobic moiety to drive the polymeric self-assembly. Free doxorubicin molecules could be encapsulated into the self-assembled nanoparticles via hydrophobic interactions and molecular π–π stacking. The results obtained show that the drug release can be triggered by the temperature with a significantly increased release being observed under acidic conditions. The cytotoxicity behaviour of the copolymers and drug-loaded nanoparticles was investigated in vitro at varying pH values and different temperatures. In doing so, superior characteristics concerning compatibility and anti-cancer activity could be observed.

CAS / MDL: 56-84-8
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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Silica Nanotubes Decorated by pH-Responsive Diblock Copolymers for Controlled Drug Release

Jiemei Zhou,Wenjian Zhang,Chunyan Hong,Caiyuan Pan

A novel nanocontainer, which has silica nanotube (SNT) core and pH-sensitive polymer shell attaching on the exterior surface of silica nanotube, is presented in this paper. Polymer nanorods, which are conveniently fabricated though polymerization-induced self-assembly and reorganization method, are used as templates for the deposition of silica to fabricate hybrid nanorods. Calcination of as-synthesized silica hybrid nanorods leads to hollow SNTs. SNTs are functionalized with reversible addition–fragmentation chain transfer (RAFT) agent, then surface RAFT polymerization is conducted to get poly(2-(diethylamino)ethyl methacrylate)-b-poly(oligo(ethylene glycol) methacrylate)-coated SNTs (SNT-PDEAEMA-b-POEGMA). Doxorubicin (DOX) can be encapsulated in SNT-PDEAEMA-b-POEGMA, and controlled release of loaded DOX is achieved by adjusting pH of the medium. In vitro cell viability and cellular internalization study confirm the potential application of this nanocontainer in drug and gene delivery.

CAS / MDL: 81-88-9
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2015 · IF 3.368

Bilayers and wormlike micelles at high pH in fatty acid soap systems

Wenlong Xu,Huizhong Liu,Aixin Song,Jingcheng Hao

Bilayers at high pH in the fatty acid systems of palmitic acid/KOH/H 2 O, palmitic acid/CsOH/H 2 O, stearic acid/KOH/H 2 O and stearic acid/CsOH/H 2 O can form spontaneously (Xu et al., 2014, 2015). In this work, the bilayers can still be observed at 25   °C with an increase of the concentration of fatty acids. We found that wormlike micelles can also be prepared in the fatty acid soap systems at high pH, even though the temperature was increased to be 50   °C. The viscoelasticity , apparent viscosity, yield stress of the bilayers were determined by the rheological measurements. Wormlike micelles were identified by cryogenic transmission electron microscopy (cryo-TEM) and emphasized by the rheological characterizations, which are in accordance with the Maxwell fluids with good fit of Cole–Cole plots. The phase transition temperature was determined by differential scanning calorimetry (DSC) and the transition process was recorded. The regulating role of counterions of fatty acids were discussed by (CH 3 ) 4 N + , (C 2 H 5 ) 4 N + , (C 3 H 7 ) 4 N + , and (C 4 H 9 ) 4 N + as comparison, concluding that counterions with appropriate hydrated radius were the vital factor in the formation wormlike micelles.

CAS / MDL: 1310-58-3
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2024 · IF 4.5

Cryptotanshinone-loaded biomimetic pH-sensitive liposomes for the treatment of liver fibrosis

Kai Liu,Bolin Zhao,Zihao Sun,Nini Luo,Xiaofang Li

Liver fibrosis is characterized by the aberrant accumulation of extracellular matrix (ECM) components, primarily due to the persistent activation of hepatic stellate cells (HSCs). It is well-known that chronic liver inflammation from various etiologies leads to hepatocellular damage, which activates HSCs, initiating and exacerbating fibrosis. This presents a significant challenge for therapeutic interventions aimed at restoring ECM balance. Here, we present CPT-pH@RLs, a novel drug delivery system consisting of pH-sensitive liposomes modified with erythrocyte membranes (RBCm), designed to deliver cryptotanshinone to the liver. The results of cellular uptake and real-time in vivo imaging indicate that the modification of RBCm reduces the uptake of CPT-pH@RLs by macrophages and prolongs the in vivo cycling time of these particles. CPT-pH@RLs effectively reduce liver inflammation by inhibiting secretion of interleukin-1β (IL-1β). Moreover, they improve liver function, decrease ECM deposition, and alleviate liver fibrosis. Our findings demonstrate that CPT-pH@RLs represent a safe and effective passive targeting drug delivery system for anti-inflammatory and ECM normalization therapies, offering a promising approach for the reversal of liver fibrosis.

CAS / MDL: 38215-36-0
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