Synthesis and Charcterization of Silane Crosslinked Hydrogel to pH Sensitive Study

Eco-friendly and biodegradable novel hydrogel were prepared by blending and solution casting method. The designed hydrogel is based on chitosan/ PEG600/Gurgam with carbon nanofiller along silane crosslinked (TEOS) with pH sensitive response to controlled release of drug in biomedical materials and agriculture industry. The various concentration of carbon nanofiller is used to analyze its effect on the fabricated hydrogel characteristics by using FTIR, SEM, TGA, swelling studies (water, buffer and ionic solution). Spectra of FTIR reflected both established and newly developed groups (like hydrogel). COOH group presence is clearly observed in this range in the carbon filler reinforced hydrogel. The SEM micrographs show that CPG0.003 had a collection of polysaccharide chains as thin helices, which is attributed to the increase in the size of porosity. TGA shows to increase concentration of nanofiller enhanced the thermal stability of the designed hydrogels at temperature 25˚C to 550˚C mass loss percentage decrease upto 20% and increase thermal stability. This pH response made these resultant hydrogels as fruitful competitor against the many reported controlled release application.

Synthesis and Characterization of Chitosan-Albumin Conjugates as pH-Sensitive Biodegradable Hydrogels

A new kind of biodegradable pH-sensitive drug delivery system was developed via chitosan-albumin conjugate hydrogel. Through changing the feeding modes of reactants, two types of hydrogels（comb-type and reticular-type） were synthesized by amidation reactions between 6-O-succinoylated N-phthaloyl chitosan and albumin. The structures and morphologies of the hydrogels were characterized by SEM. And their water swelling capacity, drug loading and releasing properties at different pH values were also investigated. It was found that the comb-type of hydrogels with looser space construction had better water swelling ratio（more than 400% of its original mass） than the reticular-type of ones did（about 180% of its original mass）. In vitro release experiments of Rifampicin show that the hydrogels provided the controlled release of the entrapped drug for more than 50 h. The drug release rates of both types of hydrogels under acidic condition were lower than those under neutral or basic condition. The introduction of albumin not only improved the hydrophilicity of chitosan, but also provided the possibility of the carrier system combining other biologically active materials more easily to fulfill the delivery and therapy functions.

Preparation and Characterization of pH-Sensitive Polyvinyl Alcohol Hydrogel for Cancer Therapy

Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the DOX-loaded polyvinyl alcohol( PVA)hydrogel was prepared by freeze-thawing technique. The swelling test and the mechanical properties of the pure PVA hydrogels were performed. In addition, the in vitro drug release profiles were examined and the in vitro antitumor efficiency against He La cells was also estimated. The results indicated that the resulting PVA hydrogels contained significant amounts of water and possessed good mechanical properties,and DOX-loaded PVA hydrogel exhibited a sustained and p H-responsive DOX release. The MTT assays also demonstrated that the released DOX could effectively inhibit the proliferation of He La cells. Thus,the cross-linked PVA hydrogel can be further developed as a promising platform for cancer therapy.

5-Fluorouracil-loaded Self-assembled pH-sensitive Nanoparticles as Novel Drug Carrier for Treatment of Malignant Tumors

In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil （5-FU）], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide （PA/SDM） conjugate] was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobicaUy modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UVNis spectrophotometer. The release profile was heavily pH-dependent around phvsiological pH, and the release rate was significantly enhanced under pH of 6.8.

pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy

Currently,the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy,owing to its precise structure,high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract,blood circulation and tumor tissues compared to other oral nanomedicines.Herein,this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on in vivo significant pH changes,which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters.The precise nano-prodrugs exhibit extraordinarily high drug loading(68.16%),electric neutrality,strong hydrophobicity,and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH.These favorable physicochemical properties can effectively facilitate gastrointestinal absorption,blood circulation stability,tumor accumulation,cellular uptake,and cytotoxicity,therefore achieving high oral relative bioavailability(358.72%)and significant tumor growth inhibition while decreasing side effects.Thus,this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.

Synthesis and Characterization of Novel Temperature and pH Responsive Hydroxylpropyl Cellulose-based Graft Copolymers

In this study, double-hydrophilic hydroxylpropyl cellulose （HPC） based copolymers with poly（N- isopropylacrylamide） （PNIPAM） and poly（acrylic acid） （PAA） as graft chains were synthesized and characterized. The release behavior of drug-loaded micelles was studied. The results show that the hydrophilicity of copolymers improves as the pH increases, whereas the hydrophobicity of copolymers enhances as the temperature increases, and all the phase behaviors are reversible. The diameter of micelles decreases and then increases with pH increase. It shows different micellizing behavior under acidic and basic conditions according to the temperature increase. In vitro release experiments, which used theophylline as a model drug, show that the micelles enhance pH sensitivity in the release process.

DESWELLING BEHAVIOR OF POLY(TETRAETHYLENEPENTAMINE EPICHLOROHYDRIN)GELS HYDROPHOBICALLY MODIFIED BY STEARIC ACID

A novel type of polysoap hydrogel based on poly(tetraethylenepentamine-epichlorohydrin)hydrophobically modified by stearic acid was prepared. The deswelling behaviors of polysoap hydrogels werestudied by immersing the gels in buffer solution at various pHs and ionic species. The deswelling of the gelsdid not depend on the cationic species of electrolyte but depended strongly on the anionic species. Acomparison of polysoap gels with the gel unmodified hydrophobically verified the importance of hydrophobicinteraction, which enhances the occurrence of deswelling rate.

Study on the Carbon Nanotube Separative Structure for the Extended Gate H^+-Ion Sensitive Field Effect Transistor

We use the carbon nanotube (CNT) as the material of the pH sensing layer of the separative structure for the extended gate H^+-ion sensitive field effect transistor (EGFET) device.The CNT paste was prepared with CNT powder,Ag powder,silicagel,the di-n-butyl phthalate and the toluene solvents by appropriate ratio,then immobilized on the silicon substrate to form the carbon nanotube sensing layer.We measured theⅠ_(DS)-Ⅴ_G curves of the carbon nanotube separative structure EGFET device in the different pH buffer solutions by the Keithley 236Ⅰ-Ⅴmeasurement system.According to the experimental results,we can obtain the pH sensitivities of the carbon nanotube separative structure EGFET device,which is 62.54mV/pH from pH1 to pH13.

Thermoreversible Thickening and Self-assembly Behaviors of pH/Temperature Dually Responsive Microgels with Interpenetrating Polymer Network Structure

The pH /temperature dually responsive microgels of interpenetrating polymer network( IPN) structure composed of poly( N-isopropylacrylamide)( PNIPAM) network and poly( acrylic acid)( PAA) network( PNIPAM /PAA IPN microgels) were synthesized by seed emulsion polymerization. The results obtained by dynamic laser light scattering( DLLS) show that the microgels have good pH /temperature dual sensitivities. The temperature sensitive component and the pH sensitive component inside the microgels have little interference with each other. The rheological properties of the concentrated PNIPAM /PAA IPN microgel dispersions as a function of temperature at pH 4. 0 or 7. 0 were investigated by viscometer,and the results displayed that only at pH 7. 0 the dispersions presented thermoreversible thickening behavior. Then the PNIPAM /PAA fibers were prepared by self-assembly of the PNIPAM /PAA IPN microgels in the ice-crystal templates formed by unidirectional liquid nitrogen freezing method. Field emission scanning electron microscopy( FESEM) images indicate that the PNIPAM /PAA fibers are rounded,randomly orientated and interweaved.

Electrical Conductivity and pH Sensitivity of Ordered Porous Gel Acrylate Polymer Membrane with Nano-PANI Doping

Electrical conductivity and pH sensitivity of nano-PANI membrane was studied. In this work,an ordered porous nano-polyaniline/acrylate gel polymer( PAGP) membrane was prepared from methyl methacrylate( MMA)/acrylic acid( AA)/nano-PANI bicontinuous microemulsions. The morphology,electric conductivity and p H sensitivity of the composite membrane were studied using scanning electronic microscopy,atomic force microscopy,and electrochemical impedance spectroscopy. It was found that the polymer matrix comprises of two types of proton migrating tunnels: interconnect hydrophilic trench( IHT) and continuous amphiphilic matrix( CAM). The increase of doped nano-PANI particles in those channels leads to a formation of three dimension grain-boundary network. It contributes to the short response time and good reversibility of the sensors. Impedance changes in the low-frequency region reveal an inductive behavior to PANI membrane,which maybe the contribution of faradaic pseudocapacitance of the polymer materials.

Equilibrium Swelling and Solute Diffusion Characteristics of Poly (Methacrylic Acid co-Poloxamer) Hydrogels

Poly(methacrylic acid co-poloxamer) hydrogel networks were synthesized by free radical solution polymerization and their equilibrium swelling and solute permeation properties were characterized. These gels exhibited pH dependant swelling and solute diffusivity due to the formation or disruption of hydrogen bonded complexation between methacrylic acid (MAA) and etheric (EO). In neutral and basic conditions (above the swelling transition pH), the copolymer swelling was greatly higher than acid condition. In complexed hydrogels, the diffusion coefficients of vitamin B12 (VB12) were in the range of 10-10 to 10-7 cm2s-1; While in uncomplexed hydrogels, the values were about 210-6 cm2s-1. The comonomer composition and synthesis conditions have great effect on the structure, and thereby, swelling and solute diffusion characteristics of the resultant hydrogels. For the copolymers with composition of less than or more than 1:1 MAA/EO molar ratio, the plot of lnD vs 1/H-1 followed two different linear equations of 慺ree volume theory? respectively.

Design,synthesis and evaluation of spermine-based pH-sensitive amphiphilic gene delivery systems: Multifunctional non-viral gene carriers

Design and development of efficient non-viral gene delivery systems is critical to overcome various barriers for effective intracellular gene delivery.Eight new spermine-based protonatable surfactants were designed,synthesized and evaluated as non-viral pH-sensitive gene carriers.These carriers formed stable complexes with plasmid DNA at an N/P ratio as low as 2.The sizes of the carrier/pDNA nanoparticles (N/P = 12) were in the range of 90–130 nm,smaller than that of Lipofectamine2000/pDNA nanoparticles.The pDNA nanoparticles of the carriers exhibited substantially increased hemolysis when pH decreased from 7.4 to 5.5.The DNA nanoparticles had low cytotocixity,similar to that of Lipofectamine-2000/pDNA nanoparticles.The pH-sensitive gene carriers with no helper lipids resulted in much higher intracellular transfection and gene expression in U87 cells than Lipofectamine-2000.[N,N′-Bis(oleoylcysteinyl)(β-alanyl-α-lysyl)]-spermine monoamide (SKACO) resulted in the highest luciferase transfection efficiency,more than 400 times higher than that of Lipofectamine-2000,and GFP expression in 71% of transfected U87 cells.SKACO was identified as a promising lead carrier for efficient gene delivery.These spermine-based pH-sensitive amphiphilic carriers have a potential to be further developed as efficient non-viral multifunctional gene delivery systems.

Dual pH and glucose sensitive gel gated mesoporous silica nanoparticles for drug delivery

A low molecular weight gelator with dual pH and glucose sensitive moieties was synthesized. The gelator penetrated in the mesopores of silica nanoparticles(MSNs) and formed low molecular weight gel(LMWG) as gate to fabricate dual pH and glucose responsive nano drug delivery system. Antidiabetic drug was loaded in the gel caped MSNs, the drug release was responsive to the pH and glucose levels and the drug release could be controlled via the stimuli sensitivity of gel.

Aptamer-coded DNA nanoparticles for targeted doxorubicin delivery using pH-sensitive spacer

An anticancer drug delivery system consisting of DNA nanoparticles synthesized by rolling circle amplification （RCA） was developed for prostate cancer membrane antigen （PSMA） targeted cancer therapy. The template of RCA was a DNA oligodeoxynucleotide coded with PSMA-targeted aptamer, drug-loading domain, primer binding site and pH-sensitive spacer. Anticancer drug doxorubicin, as the model drug, was loaded into the drug-loading domain （multiple GC-pair sequences） of the DNA nanoparticles by intercalation. Due to the integrated pH-sensitive spacers in the nanoparticles, in an acidic environment, the cumulative release of doxorubicin was far more than the cumulative release of the drug in the normal physiological environment. In cell uptake experi- ments, treated with doxorubicin loaded DNA nanoparti- cles, PSMA-positive C4-2 cells could take up more doxorubicin than PSMA-null PC-3 cells. The prepared DNA nanoparticles showed the potential as drug delivery system for PSMA targeting prostate cancer therapy.

pH-Sensitive Wettability Induced by Topological and Chemical Transition on the Self Assembled Surface of Block Copolymer

pH-sensitive wettability of polystyrene-b-poly（4-vinylpyridine） （PS-b-P4VP） self assembled films, exhibiting superoleophobicity under water and hydrophilicity at low pH value, and oleophobicity under water and hydrophobicity at neutral condition, has been realized. The wettability properties resulted from the surface topological and chemical transition, which were confirmed by in situ AFM measurements under water at different pH. At low pH, P4VP chains, which were confined in the hexagonal-packed nanodomains, got protonated into a swollen state, while at high pH, P4VP chains were deprotonated into a collapsed state. The reversible protonation/deprotonation procedure on the molecular scale leads to surface topological and chemical transition, thereby pH-sensitive wettability.

A biomimetic and pH-sensitive polymeric micelle as carrier for paclitaxel delivery

As nano-scale drug delivery systems,smart micelles that are sensitive to specific biological environment and allowed for target site-triggered drug release by reversible stabilization of micelle structure are attractive.In this work,a biocompatible and pH-sensitive copolymer is synthesized through bridging poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC)block and poly(D,L-lactide)(PLA)block by a benzoyl imine linkage(Blink).Biomimetic micelles with excellent biocompatibility based on such PLA-Blink-PMPC copolymer are prepared as carriers for paclitaxel(PTX)delivery.Due to the rapid breakage of the benzoyl imine linkage under acidic condition,the micelle structure is disrupted with accelerated PTX release.Such pH-sensitive triggered drug release behavior in synchronization with acidic conditions at tumor site is helpful for improving the utilization of drug and facilitating antitumor efficacy.These micelles can be used as promising drug delivery systems due to their biocompatible and smart properties.

Synthesis and Properties of Poly (N-isopropylacrylamide) and Poly (N-isopropylacrylamide-co-acrylamide) Hydrogels

The thermosensitive poly （ N-isopropylacrylamide ） （PNIPAAm） and poly （N-isopropylacrylamide-co-acrylamide） [ poly （NIPAAm-co-AAm） ] hydrogels with different acrylamide molar percentage are prepared by radiation polymerization using Co^60 γ-ray. Their swelling equilibrium data in the media of deionized water, NaCl aqueous solutions and different pH buffer solutions are determined. It appears that lower critical solution temperature （LCST） of the hydrogels will drop with the increase of ionic strength and increase with the rising of acrylamide content, A semi-empirical formula is set up with the experimental results. Moreover, it also indicates that this copolymer is pH-sensitive, which is similar to the homopolymer of PNIPAAm.

Poly(N-isopropylacrylamide), Poly(methacrylic acid) and Their Copolymers for Oral Colon-specific Drug Delivery

A series of cross-linked gels of Poly（N-isopropylacrylamide） [P（NIPAAm）] and Poly（methacr-ylic acid）[P（MAA）] homopolymers and P（NIPAAm-co-MAA） random copolymers were synthesized based on NIPAAm and MAA using 4,4-Bis-（methacryloylamino） azobenzene （BMAAB） as a cross-linker. The swelling behavior of these hydrogels in different pH buffer solutions was studied. The influential factors of the gels including composition of NIPAAm and MAA, pH and temperature upon swelling behavior were investigated. The obtained gels not only hold pH and thermometrical sensitivity, but also take on enzymatic sensitivity due to the cross-linker could be degraded by enzymes of colon. Swelling equilibrium degree of copolymers was very low in acidic medium, which could avoid drug releasing due to biggish swelling of carder in stomach. Hydrogels would partly swell owing to higher pH value in small intestine. When arrived in colon, hydrogels completely swelled, meanwhile, azoenzymes located would degrade azo-bonds of polymeric network and then drug released in colon.

Short and simple peptide-based pH-sensitive hydrogel for antitumor drug delivery

Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for drug delivery. In this study, we developed a novel and injectable drug delivery platform for the antitumor drug doxorubicin(DOX) using a p H-responsive ionic-complementary octapeptide FOE.This octapeptide could self-assemble into stable hydrogel under neutral conditions, while disassemble under the tumor microenvironment. Especially, at p H 5.8, its micromorphology displayed a transition from nanofibers to nanospheres with the change of secondary structure, which enhanced cellular uptake of DOX. In addition, FOE hydrogel serves as a smart drug reservoir by localized injection to achieve sustained drug release and improve antitumor efficacy. This octapeptide opens up new avenues for promoting the clinical translation of anticancer drugs on account of excellent injectable properties and economic benefits of simple and short sequence.

Chitosan-g-PAA Hydrogels for Colon-Specific Drug Delivery: Preparation, Swelling Behavior and in vitro Degradability

A series of cross-linked hydrogels for colon-specific drug delivery were synthesized by graft copolymerization of Chitosan and acrylic acid using N, N＇-methylene-bis-（acrylamide） as a cross-linker. Their swelling behavior in different pH buffer solutions and colonic enzymatic degradability were studied. The obtained results show that these hydrogels have good pH sensitivity which can avoid drug release in stomach, and their swelling kinetics in stimulant intestinal environment follow second-order swelling kinetics equation. The factors influencing the swelling kinetics include the degree of cross-linking and the composition, which may control no release or a little amount release of drug inside the hydrogels in the small intestine by tailoring these factors. The gels are degradable by colonic enzymes and there is a correlativity between the degradation of networks and the swelling degree of the gels, which may trigger the release of drug in the colon. The hydrogels show a great potential for their application in oral colon-specific drug delivery system.