Polymerization Of N-isopropylacrylamide Research Articles

Preparation and Application of Responsive Nanocellulose Composites

Cellulose nanofibrils/poly(N-Isopropylacrylamide) semi-interpenetrating networks (MMCNF-PNAs) were synthesized using an in situ fabrication (semi-IPN). The polymerization of N-isopropylacrylamide (NIPAM) (free radical) was conducted in the presence of magnetic modified cellulose nanofibrils (MMCNFs). The adsorption behaviors and surface morphology of the synthesized adsorbents were investigated systematically. The adsorption behaviors of the as-prepared MMCNF-PNA towards methylene blue (MB, as the model contaminant) dye was studied, and the optimal adsorption conditions were also studied. The adsorption processes could be well fitted using pseudo-second-order and Elovich kinetic models. Meanwhile, Langmuir and Freundlich isotherm models were used to fit the adsorption which occurred at 25, 37 and 65 °C. The corresponding results showed that the Freundlich isotherm model fitted the adsorption process better, indicating that the dye’s adsorption happened via heterogeneous adsorptive energies on the prepared MMCNF-PNAs. Their desorption and reusability were also studied to verify magnetic responsivity. To sum up, MMCNF-PNAs are promising magnetic and thermal stimuli-responsive adsorbents, showing a controlled adsorption/desorption process.

Photoinduced Metal-Free Atom Transfer Radical Polymerization for the Modification of Cellulose with Poly(N-isopropylacrylamide) to Create Thermo-Responsive Injectable Hydrogels.

Photoinduced metal-free ATRP has been successfully applied to fabricate thermo-responsive cellulose graft copolymer (PNIPAM-g-Cell) using 2-bromoisobuturyl bromide-modified cellulose as the macroinitiator. The polymerization of N-isopropylacrylamide (NIPAM) from cellulose was efficiently activated and deactivated with UV irradiation in the presence of an organic-based photo-redox catalyst. Both FTIR and 13C NMR analysis confirmed the structural similarity between the obtained PNIPAM-g-Cell and that synthesized via traditional ATRP methods. When the concentration of the PNIPAM-g-Cell is over 5% in water, it forms an injectable thermos-responsive hydrogel composed of micelles at 37 °C. Since organic photocatalysis is a metal-free ATRP, it overcomes the challenge of transition-metal catalysts remaining in polymer products, making this cellulose-based graft copolymer suitable for biomedical applications. In vitro release studies demonstrated that the hydrogel can continuously release DOX for up to 10 days, and its cytotoxicity indicates that it is highly biocompatible. Based on these findings, this cellulose-based injectable, thermo-responsive drug-loaded hydrogel is suitable for intelligent drug delivery systems.

A 4D Printed Adhesive, Thermo-Contractile, and Degradable Hydrogel for Diabetic Wound Healing.

Chronic wound healing remains a substantial clinical challenge. Current treatments are often either prohibitively expensive or insufficient in meeting the various requirements needed for effective diabetic wound healing. A 4D printing multifunctional hydrogel dressing is reported here, which aligns perfectly with wounds owning various complex shapes and depths, promoting both wound closure and tissue regeneration. The hydrogel is prepared via digital light process (DLP) 3D printing of the mixture containing N-isopropylacrylamide (NIPAm), curcumin-loaded Pluronic F127 micelles (Cur-PF127), and poly(ethylene glycol) diacrylate-dopamine (PEGDA575-Do), a degradable crosslinker. The use of PEGDA575-Do ensures tissue adhesion and degradability, and cur-PF127 serves as an antibacterial agent. Moreover, the thermo-responsive mainchains (i.e., polymerized NIPAm) enables the activation of wound contraction by body temperature. The features of the prepared hydrogel, including robust tissue adhesion, temperature-responsive contraction, effective hemostasis, spectral antibacterial, biocompatibility, biodegradability, and inflammation regulation, contribute to accelerating diabetic wound healing in Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect diabetic rat models and liver injury mouse models, highlighting the potential of this customizable, mechanobiological, and inflammation-regulatory dressing to expedite wound healing in various clinical settings.

Feasibility evaluation of N-Isopropyl Acrylamide 3D gel dosimeters for proton therapy.

This study aimed to investigate the feasibility of applying 3D gel dosimeters for proton therapy. Two different formulations (5-5-3-5, 5-3-3-10) for the N-Isopropyl Acrylamide (NIPAM) polymer gel were used to find the best composition for the application of NIPAM polymer gels for proton therapy. The reaction of the gel under different physical conditions, including dependence on energy and dependence on the dose rate of the NIPAM gel under proton irradiation, was also explored. A NIPAM gel dosimeter was used to record the 3D dose distribution, and a self-developed parallel beam optical computed tomography scanner was used to obtain non-irradiated and post-irradiated gel phantom images. The NIPAM gel was filled into a cylindrical acrylic phantom. The results showed that the optical density of the irradiated NIPAM dosimeter was linear in the dose range of 0 to 6 Gy, and the linearity of the two NIPAM gel formulations at the depth of the dose point (2 cm) was 0.98 to 0.89. The dose depth curves showed different patterns with different gel sensitivities. This study demonstrated that the NIPAM gel dosimeter with the 5-3-3-10 formulation is suitable for verifying the dosimetry dose of proton beams.

The advanced polymer composite coated fabrics as an anode electrode and photocatalytic glucose micro fuel cell design

At present, poly N-isopropyl acrylamide (PNIPAM) polymer composites containing titanium dioxide (TiO2) and carbon-TiO2 (C-TiO2) were designed for photocatalytic glucose electrooxidation by coating the textile fabric surface such as wool blended fabrics called Sign Cocana (SC), Valencia (VC), Dante (DT), and Broadway (BW). C-TiO2 was obtained from TiO2 in a furnace under hexane gas with a certain temperature and time. Polymer synthesis was realized by a polymerization method. The surface analyses of these polymer composite fabric electrodes were characterized by scanning electron microscopy-energy dispersive X-Ray (SEM-EDX) and mapping analysis. In addition, tear and breaking strengths were examined. Photocatalytic activity of the polymer composite electrodes was examined by cyclic voltammetry (CV). The C-TiO2-graft(g)-PNIPAM/SC electrode exhibited the best photocatalytic activity under UV illumination with a specific activity of 2.80 mA/cm2 both in the dark and compared to other fabric electrodes. In addition, it was observed that it exhibited the best stability and resistance by chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS) analyses. It could be a promising anode electrode for photocatalytic fuel cells and wearable electronics.

Temperature-sensitive amphiphilic nanohybrid as rheological modifier of water-in-oil emulsion drilling fluid: Preparation and performance analysis

In our previous study, as a rheological modifier for flat rheology water-based drilling fluid, binary composite temperature-sensitive SiO2 nanohybrid was successfully synthesized and characterized [J. Petrol. Sci. Eng. 219 (2022), 111,096]. The aim of this study was to investigate the flat rheological characteristics of emulsion drilling fluid, a temperature-sensitive amphiphilic ternary composite nanohybrid was prepared via the copolymerization of temperature sensitive polymer monomers N-isopropylacrylamide (NIPAM) and methylallyl alcohol (MAA) in the presence of nano-silica surface-capped by modifier containing double bond (denoted as SiO2-D). The as-prepared PNM/SiO2-D (PNM refers to polymerized NIPAM and MAA) nanohybrid was characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy and transmission electron microscopy. Findings indicate that PNM/SiO2-D nanohybrid has a three-dimensional network structure and a particle size of 20–30 nm. Rheological properties of PNM/SiO2-D nanohybrid in aqueous solution, water-in-oil (W/O) emulsion system and W/O emulsion drilling fluid system were investigated, respectively. And the results revealed that PNM/SiO2-D nanohybrid as a rheological modifier is more sensitive to temperature in the emulsion with a high water-oil ratio, and significantly increase the viscosity of the emulsion system at elevated temperatures. Furthermore, the W/O emulsion drilling fluid with a water-oil ratio of 4:6 exhibits higher modulus values than the one with a water-ratio of 1:9, due to the better suspending capacity of the former for drill cuttings under static conditions, which could ensure the application of emulsion drilling fluid in drilling process.

Point-of-care assay platform for uric acid, urea, and triglycerides with a microfluidic paper device (μPAD) controlled by stimulus-sensitive valves

A microfluidic biosensor paper-based analytical device, or μPAD, was developed as a point-of-care assay platform for the simultaneous determination of three clinically important markers: uric acid, urea, and triglycerides. To achieve a simultaneous determination, thermosensitive valves based on N-isopropylacrylamide polymers controlled the flow of fluid in the μPAD. The evaluation of the analytical characteristics of the μPAD was done using a photographic camera at room temperature.The detection limits were 4.5·10−5, 2.5·10−3, and 1.5·10−3 mg mL−1, for uric acid, urea, and triglycerides, respectively, and the precision expressed as relative standard deviation (% RSD) 3.2, 1.2, and 1.6%. The obtained μPAD devices were validated with real human plasma samples, demonstrating high accuracy and precision. Multiple analyte point-of-care tests such as those developed here have excellent characteristics, being easy to manufacture, cost-effective, easy to use, and highly sensitive.

The onset of mass transport limitations triggers the stimulus responsiveness of polymer coated catalysts

A series of Pd/Al2O3 catalysts coated with N-isopropylacrylamide polymer (p-NIPAM) brushes with increasing particle size of the support were prepared to study the interplay between mass transport limitations and the ability of the thermo-responsive catalysts to modify reactivity during reaction. Nitrite hydrogenation in water was chosen as probe reaction, which is a key step in the reduction of nitrites and nitrates from drinking water. The results show that the apparent activation energy decreases on increasing temperature above the LCST, i.e. the temperature where the polymer undergoes a phase change, for catalyst with particle sizes between 38 and 100 μm, alluding to a significant increase in mass transfer limitations. In sharp contrast, both p-NIPAM modified catalysts with smaller particle size and uncoated catalysts do not show this change in activation energy with temperature. Detailed multi-physics mass transport and reaction modelling indicated that the transport of the limiting reagent, hydrogen in this case, is severely reduced when the p-NIPAM collapses at temperatures above its LCST. It is concluded that effective reaction control using stimulus responsive polymers requires the system to be close to the mass transport limitation regime, to maximize the effect of the conformation change of the polymer on the catalyst performance and achieve sharp and reversible transitions from active to inactive.

Properties in Langmuir Monolayers and Langmuir-Blodgett Films of a Block Copolymer Based on N-Isopropylacrylamide and 2,2,3,3-Tetrafluropropyl Methacrylate

The amphiphilic block copolymer poly(N-isopropylacrylamide)-Ge(C6F5)2-poly(2,2,3,3-tetrafluoropropyl methacrylate) was prepared by the reaction of chain transfer to bis-(pentafluorophenyl)germane during the polymerization of N-isopropylacrylamide and the subsequent postpolymerization of isolated functional polymers in 2,2,3,3-tetrafluoropropyl methacrylate. The conversion of the block copolymer was 68% and the molecular weight of the sample was 490,000 g/mol. The colloidal chemical properties of Langmuir monolayers and Langmuir-Blodgett films of synthesized block copolymer have been studied. For comparison, a functional polymer, namely, poly-N-isopropylacrylamide with terminal -Ge(C6F5)2H group, was synthesized and studied. The concentrations of spreading solutions were selected and the effect of subphase acidity on the formation of monolayers of macromolecules of the block copolymer was studied. It was found that regardless of the acidity of the subphase, high pressure of fracture of films are characteristic of monolayers of collapse pressures πmax = (48-61) mN/m. The morphology of the Langmuir-Blodgett films of functional polymer exhibit isolated elongated micelles with high densities in the form of "octopus" on the periphery of which there are terminal hydrophobic groups. For the Langmuir-Blodgett film of block copolymer, a comb-like structure is observed with characteristic protrusions.

Preparation of Temperature-Responsive Antibody-Nanoparticles by RAFT-Mediated Grafting from Polymerization.

Herein, we report the preparation of temperature-responsive antibody-nanoparticles by the direct polymerization of N-isopropylacrylamide (NIPAAm) from immunoglobulin G (IgG). To this end, a chain transfer agent (CTA) was introduced into IgG, followed by the precipitation polymerization of NIPAAm in an aqueous medium via reversible addition-fragmentation chain transfer polymerization above the lower critical solution temperature (LCST). Consequently, antibody-polymer particles with diameters of approximately 100-200 nm were formed. Owing to the entanglement of the grafted polymers via partial chemical crosslinking, the antibody-nanoparticles maintained their stability even at temperatures below the LCST. Further, the dispersed nanoparticles could be collected by thermal precipitation above the LCST. Additionally, the antibody-nanoparticles formulation could maintain its binding constant and exhibited a good resistance against enzymatic treatment. Thus, the proposed antibody-nanoparticles can be useful for maximizing the therapeutic potential of antibody-drug conjugates or efficacies of immunoassays and antibody recovery and recycling.

Investigating the Sensitivity of New Formulation MAGAT and NIPAM Polymer Gels in the Radiation Therapy Dosimetry.

Background: Normoxic polymer gels have been used as a three dimensional (3D) dosimeter in radiation therapy, recently. The sensitivity of these gels is important in dosimetry and their improvement can be also useful.Objective: In this study, different modalities of gel reading were used and the structure of gel changed due to the best improvement of sensitivity. The sensitivities of the new formulation of Methacrylic acid gel (MAGAT) and N-isopropyl acrylamide (NIPAM) polymer gel dosimeters were studied using two different reading methods of magnetic resonance imaging (MRI) and X-ray computed tomography (X-ray CT).Material and Methods: In this experimental study, in addition to making the NIPAM polymer gel dosimeter, a new formulation of normoxic polymer gel dosimeter, which named MAGAT gel, was investigated. The gels were irradiated with 6 MV in low doses, including1, 1.5, 1.75, 2 and 2.5 Gy. MRI and X-ray CT did the reading of gel dosimeters a day after irradiation using an elevated protocol.Results: The dose sensitivities of 0.92 HGy-1 and 0.47 HGy-1 were obtained for new MAGAT and NIPAM polymer gel dosimeters, respectively, based on the X-ray CT reading modality. The use of MRI reading modality and the dose sensitivities were 0.74 S-1Gy-1 and 0.27 S-1Gy-1 for new MAGAT and NIPAM polymer gel dosimeters, respectively.Conclusion: The new formulation of MAGAT polymer gel with a suitable protocol of gel reading has a better response.

Fabrication of Thermo-Responsive Controllable Shape-Changing Hydrogel.

Temperature response double network (DN) hydrogels comprising a network formed by polymerization of methacrylic acid (MA) modified PVA, N,N’-methylene bis(acrylamide), N-isopropylacryl amide (NIPAM), and one formed from crystalline polyvinyl alcohol (PVA) are prepared in a 3D printed tailor-made mold. The (PVA-MA)-g-PNIPAAm thermoset intermediate is formed in water by a radical, photo-initiated process, and in the presence of dissolved PVA polymers. A subsequent freezing-thawing sequence induces the crystallization of the PVA network, which forms a second network inside the thermoset NIPAM polymer. The prepared hydrogel is thermoresponsive by the phase transition of PNIPAAm segments (T ≈ 32 °C) and has good mechanical properties (tensile strength 1.23 MPa, compressive strength 1.47 MPa). Thermal cycling between room temperature at 40 or 50 °C shows the product converses from a virgin-state to a steady-state, which most likely involves the reorganization of PVA crystals. The swelling-deswelling cycles remain clear at a length change of about 13%.

PNIPAM/Hexakis as a thermosensitive drug delivery system for biomedical and pharmaceutical applications

Many technologies ranging from drug delivery approaches to tissue engineering purposes are beginning to benefit from the unique ability of “smart polymers.” As a special case, thermo-sensitive hydrogels have great potential, e.g. in actuators, microfluidics, sensors, or drug delivery systems. Here, the loading of Doxorubicin (DOX) with novel thermo-sensitive polymer N-isopropyl acrylamide (PNIPAM) and its copolymers are investigated in order to increase the Doxorubicin’s drug efficacy on the targeted tumor site. Therefore, a rational design accurate based on the use of classical molecular dynamics (MD) and well-tempered metadynamics simulations allows for predicting and understanding the behavior of thermo-responsive polymers in the loading of DOX on Hexakis nano-channel at 298 and 320 K. Furthermore, this work investigates the efficacy of this drug carrier for the release of DOX in response to stimuli like variations in temperature and changes in the physiological pH. The study concludes that the Hexakis–polymer composite is capable of adsorbing the DOX at neutral pH and by increasing the temperature of the simulated systems from 298 to 320 K, the strength of intermolecular attraction decreases. In addition, the obtained results of MD simulation revealed that the dominant interaction between DOX and Hexakis in the DOX/polymer/Hexakis systems is the Lennard–Jones (LJ) term due to the formation of strong π–π interaction between the adsorbate and substrate surface. Obtained results show that a higher aggregation of DMA chains around the Hexakis and the formation of stronger bonds with DOX. The results of the well-tempered metadynamics simulations revealed that the order of insertion of drug and polymer into the system is a determining factor on the fate of the adsorption/desorption process. Overall, our results explain the temperature-dependent behavior of the PNIPAM polymers and the suitability of the polymer–Hexakis carrier for Doxorubicin delivery.

Quantification of Metabolic Products from Microbial Hosts in Complex Media Using Optically Diffracting Hydrogels.

We herein describe a highly versatile platform approach for the in situ and real-time screening of microbial biocatalysts for enhanced production of bioproducts using photonic crystal hydrogels. This approach was demonstrated by preparing optically diffracting films based on polymerized N-isopropylacrylamide that contracted in the presence of alcohols and organic acids. The hydrogel films were prepared in a microwell plate format, which allows for high-throughput screening, and characterized optically using a microwell plate reader. While demonstrating the ability to detect a broad range of relevant alcohols and organic acids, we showed that the response of the films correlated strongly with the octanol-water partition coefficient (log P) of the analyte. Differences in the secretion of ethanol and succinic acid from strains of Zymomonas mobilis and Actinobacillus succinogenes, respectively, were further detected via optical characterization of the films. These differences, which in some cases were as low as ∼3 g/L, were confirmed by high-performance liquid chromatography, thereby demonstrating the sensitivity of this approach. Our findings highlight the potential utility of this multiplexed approach for the detection of small organic analytes in complex biological media, which overcomes a major challenge in conventional optical sensing methods.

Reversible light-controlled fluorescence switch of block polymer-grafted carbon dots and cellular imaging.

A novel type of aggregation-induced emission (AIE) nanoparticles, which are carbon dots (CDs) grafted with block polymer of tetraphenylethylene, spiropyran and N-isopropylacrylamide (CD-g-poly((TPE-co-SPA)-block-NIPAM)), was synthesized. The CD-g-poly((TPE-co-SPA)-block-NIPAM) nanoparticles can emit weak cyan fluorescence in tetrahydrofuran, while showing AIE-enhanced cyan fluorescence in water and solid film. The fluorescence of the CD-g-poly((TPE-co-SPA)-block-NIPAM) nanoparticles can reversibly transform cyan to red with UV/visible light irradiation, and functioned as a reversible fluorescence photoswitch. Importantly, the CD-g-poly((TPE-co-SPA)-block-NIPAM) nanoparticles have low cytotoxicity and, therefore, can be used for imaging in living cells.

Tetraphenylethylene and N-isopropylacrylamide block polymer-grafted carbon dots with their application in cellular imaging

Carbon dots (CDs) grafted with block polymer of tetraphenylethylene (TPE) and N-isopropylacrylamide (CD-g-poly(TPE-block-NIPAM)) were synthesized, which are aggregation-induced emission (AIE) nanoparticles. The CD-g-poly(TPE-block-NIPAM) exhibited different fluorescence behaviors in tetrahydrofuran (THF) and water. In THF, the CD-g-poly(TPE-block-NIPAM) could fluoresce, but only from CDs, and the TPE block showed no fluorescence. The fluorescence of CDs was quenched ,and the TPE block showed AIE, when the CD-g-poly(TPE-block-NIPAM) were dispersed in water. The CD-g-poly(TPE-block-NIPAM) showed no cytotoxicity, which could be easily internalized by human breast cancer cells and human embryonic kidney cells with high fluorescence, and they can be used as fluorescent tracers for living cells.

High-sensitivity and temperature-controlled switching methanol sensor prepared based on the dual catalysis of copper particles

In this work, based on the dual catalytic properties of copper (Cu) particles for methanol oxidation and persulfate initiated radical polymerization, a temperature-controlled catalytic electrode, defined the PNIPAM-Cu@CP, was constructed by electrodepositing Cu particles on a carbon paper electrode and triggering the polymerization of the temperature-sensitive polymer N-isopropylacrylamide (PNIPAM) on the surface of the electrode, which is expected to be applicated in the micro-direct methanol fuel cell (DMAC) for detection of methanol crossover and also has temperature recognition and high-temperature self-protection functions. Cu particles and PNIPAM were characterized by X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) for their specific structure and morphology. The cyclic voltammetry (CV) results showed the proposed electrode as a temperature-controlled switch-like methanol sensor, has a wide linear range (1–300 mM and 300–1200 mM), excellent sensitivity (72.8 μA cm−2 mM−1 and 11.5 μA cm−2 mM−1) and a low detection limit of 0.3 mM for methanol. In addition, the sensor also has excellent selectivity and temperature-triggered switchable electrocatalytic activity. The efficient and simple preparation method of the electrode is expected to be used in the development of a methanol sensor for real-time methanol detection in micro-DMAC.

N-isopropylacrylamide polymer brushes alter the micro-solvation environment during aqueous nitrite hydrogenation on Pd/Al2O3 catalyst

Nitrite contaminants in freshwater streams, resulting from run-off of fertilizers and livestock farming, are a major ecological challenge. Here, we have developed a new family of catalysts based on Pd/Al2O3 coated with N-isopropylacrylamide polymer (p-NIPAM) brushes that increase N-N bond formation over N-H bond formation, promoting nitrogen selectivity by 3-fold, reaching >99% for the Pd/Al2O3 containing 20 wt% carbon in the form of p-NIPAM, without significant drops in catalytic activity (TOF of c.a. 6.8 ± 1.1 min−1). Strikingly, rigorous mass transport studies revealed that the presence of p-NIPAM does not limit the transfer of molecules during the hydrogenation of nitrites in aqueous phase. These observations were corroborated by detailed reaction kinetics in which similar activation barriers for nitrites disappearance of 30–34 kJ mol−1 were obtained regardless the polymer content. The observed reaction orders for nitrites were similar on the coated and un-coated catalysts, indicating that the rate determining step, most likely NOX-H bond formation, remained unaltered. The apparent barriers for ammonia formation, however, drastically increased from 41 ± 3 kJ mol−1 on Pd/Al2O3 to 63 ± 4 kJ mol−1 and 76 ± 5 kJ mol−1 on the 7 and 20 wt% C counterparts, respectively. Contrary to the widely accepted operation mode of thermo-responsive catalysts containing p-NIPAM brushes, we demonstrated that these polymers modify the chemical environment near the active site as shown by in-situ ATR data, tunning the catalyst selectivity without altering the molecular transport. These results will facilitate the development of more selective catalysts for liquid phase reactions relevant for drinking water purification.

PEG-Induced Controllable Thin-Thickness Gradient and Water Retention: A Simple Way to Programme Deformation of Hydrogel Actuators.

Building the differential growth through the thickness is a promising and challenging approach to design the morphing structures of hydrogel actuators. Besides retaining the size of the hydrogel actuators under environmental stimuli still remains a big challenge. Herein, a facile and universal approach is developed to address both issues by introducing PEG during the polymerization of N-isopropylacrylamide (NIPAm) via one step method using asymmetric mold. Both composition gradient and pore gradient are obtained in micro level along the thickness direction of the final hydrogel, while thin-thickness gradient in macro level. The thickness gradient and water retention can be controllably adjusted by changing PEG concentration. The introduction of PEG effectively improves both responsive and non-shrunken performance by the interaction with PNIPAm. The resultant anisotropic PNIPAm/PEG hydrogel respond quickly and reach maximum deformation (360°) within 10 s at low temperature (40 °C).The various 3D shape and biomimetic movement can be programmed by simply controlling the PEG concentration and mold shape. This strategy can provide new insights into the design intelligent soft materials with 3D morphing for bioinspired and biomedical applications.

Modulation of phase transition of poly(N‐isopropylacrylamide)‐based microgels for pulsatile drug release

AbstractThis work aims to synthesize poly(N‐isopropylacrylamide)‐based microgels with sharp phase transition by introducing a specific secondary structure to achieve pulsatile drug release near body temperature. To achieve this, N‐isopropylacrylamide (NiPAM) based microgels were synthesized by surfactant free‐radical polymerization of NiPAM in the presence of polyalanine terminated α‐methallyl poly(ethylene glycol) ether (HPEG‐Alax) as a macro‐comonomer and N,N′‐methylene bisacrylamide (MBA) as a chemical crosslinker. A series of microgels were characterized by TEM, DLS, UV–Vis, 1H NMR, and other analytical methods. The introduction of hydrophilic HPEG allows the volume phase transition temperature (VPTT) to move towards the body temperature, and α‐helix structure confers a high deswelling ratio and response sensitivity to the microgel, overcoming the disadvantage of a broadened phase transition caused by hydrophilic monomers. The presence of HPEG‐Alax significantly improves the stability of the microgel in the electrolyte solution at high temperatures. The drug release of the microgels was investigated with the model drugs, hydrophilic DOX and hydrophobic curcumin, showing that the microgels can release hydrophilic drugs in a pulsatile mechanism.