pH-responsive Polymer Research Articles

Encapsulation and delivery of phage as a novel method for gut flora manipulation in situ: A review.

Intestinal flora regulation is an effective method to intervene and treat diseases associated with microbiome imbalance. In addition to conventional probiotic supplement, phage delivery has recently exhibited great prospect in modifying gut flora composition and regulating certain gene expression of gut bacteria. However, the protein structure of phage is vulnerable to external factors during storage and delivery, which leads to the loss of infection ability and flora regulation function. Encapsulation strategy provides an effective solution for improving phage stability and precisely controlling delivery dosage. Different functional materials including enzyme-responsive and pH-responsive polymers have been used to construct encapsulation carriers to protect phages from harsh conditions and release them in the colon. Meanwhile, diverse carriers showed different characteristics in structure and function, which influenced their protective effect and delivery efficiency. This review systematically summarizes recent research progress on the phage encapsulation and delivery, with an emphasis on function properties of carrier systems in the protection effect and colon-targeted delivery. The present review may provide a theoretical reference for the encapsulation and delivery of phage as microbiota modulator, so as to expedite the development of functional material and delivery carrier, as well as the advances in practical application of intestinal flora regulation.

A cyclic brush zwitterionic polymer based pH-responsive nanocarrier-mediated dual drug delivery system with lubrication maintenance for osteoarthritis treatment.

Enhanced joint synergistic lubrication combined with anti-inflammatory therapy is an effective strategy to delay the progression of early osteoarthritis (OA) but has been rarely reported. The hydration lubrication of zwitterions and inherent super-lubrication properties of the cyclic brush, as well as the enhancement of the steric stability of the cyclic topology, can effectively improve the drug loading and utilization; herein we report a pH-responsive cyclic brush zwitterionic polymer (CB) with SBMA and DMAEMA as brushes and a cyclic polymer (c-P(HEMA)) as the core template, possessing a low coefficient of friction (0.017). After loading with hydrophobic curcumin and hydrophilic loxoprofen sodium it demonstrates high drug-loading efficiency. In vitro and in vivo experiments confirmed the triple function of the CB on superlubrication, sequence controlled release and anti-inflammatory effects demonstrated by Micro CT, histological analysis and qRT-PCR. Overall, the CB is a promising long-acting lubricating therapeutic agent, with potential for OA treatment or other diseases.

Ultrahigh magnetic resonance contrast switching with water gated polymer-silica nanoparticles.

Very high T1 magnetic resonance imaging (MRI) switches can be obtained with pH-responsive polymer-coated paramagnetic mesoporous silica nanoparticles (MSNs), as the local environment traverses the pKa of the polymer coat (Δr1 ∼ 50 mM-1 s-1 at 1.5 T and Δr1 ∼ 22 mM-1 s-1 at 3 T). We assign these characteristics to a strong peripheral hydration capping at the mesopores, impacting channel-confined water mobility such that outer sphere contributions to contrast are greatly enhanced.

PH-Regulated Ionic Diode Based on an Asymmetric Shaped Multiple-Layer Polymer Membrane

Smart artificial ion channels with tunable properties have wide applications in many fields to achieve ion transport manipulation. Most reported artificial ions are constructed with vertical structures, limiting the further integration of ionic diodes into complex iontronic systems. Inspired by the asymmetric concentration polarization induced by the asymmetric geometry of nanochannels, a novel method is developed to construct horizontally arranged and pH-regulated ionic diodes in nanofluidic chips by self-assembling pH-responsive polymers. The effects of the fabrication and operation parameters on the performance of the ionic diode are systematically investigated. The current rectification ratio of the ionic diode can be modulated flexibly by regulating the pH conditions of the working fluid. An ionic diode bridge circuit for rectifying alternating current signals is built in a single nanofluidic chip and demonstrated, highlighting the feasibility of the ionic diode for complex iontronic system integration. The method presented in this paper provides a promising platform for the development of smart nanofluidic iontronic devices with widespread applicability in biological analysis, sensing, and logic computing.

Aptamer-functionalized pH-responsive polymer-modified magnetic nanoparticles for specific enrichment and sensitive determination of lactoferrin

Anew type of aptamer-functionalized pH-responsive polymer-modified magnetic nanoparticles (ApMNPs) is introduced for specific enrichment and sensitive determination of lactoferrin (Lf) in complex matrixes. In the construction, Fe3O4@3-(Triethoxysilyl)propylmethacrylate@poly(4-Vinyl-1, 3-dioxolan-2-one-acrylic acid) (Fe3O4@MPS@p(VEC-AA)) were synthesized as pH-responsive polymer-modified magnetic nanoparticles (pMNPs) through free radical polymerization to increase the tunable interaction. Lf-binding aptamers were conjugated onto pMNPs through the reaction of amino-group in aptamer and epoxide-group in VEC, innovatively applied to prepare Lf-ApMNPs. On the basis of the synergistic effect of specific affinity of aptamer on Lf and tunable hydrophobic/hydrophilic property of pH-responsive polymer, Lf-ApMNPs presented good selectivity toward Lf, excellent adsorption capacity (as high as 233.9mgg-1), as well as good recoveries in the range 93.6-99.6% in Lf-related nutrition samples. Significantly, the introduction of pH-responsive monomer (AA) effectively regulated the adsorption-desorption process of Lf, with the function similar to a switch. Moreover, the good performances of Ct-ApMNPs toward α-Chymotrypsin showed that ApMNPs exhibited universality to other proteins through easily changing the binding aptamer, thereby offering a facile and efficient approach for specific enrichment and sensitive determination of targets in real biological samples.

Preparation and characterization of crosslinked starch-albumin films for coating of prednisolone tablets for use in Covid-19 related respiratory disease

Steroidal products have been found useful in inflammations associated with Covid 19. Prednisolone is one readily available steroid, which is often found as uncoated normal release tablets. Modified release prednisolone may be desirable in Covid 19 for sustained actions. This is expected to reduce dosing frequency and enhance compliance. This study is concerned with development of controlled release prednisolone using coating technology with bio-compatible, cross-linked starch-albumin films. Starches and proteins are excellent film formers with good flexibility, transparency, and bio-compatibility. The cross-linked starch-albumin films were prepared using glycerol as the plasticizer: starch (A), starch-albumin (B), starch-albumin cross-linked with formaldehyde at 1 % (C), 5 % (D) and 10 % (E). Equilibrium moisture sorption (EMS) at 100 % relative humidity, equilibrium swelling (ESC) in buffer solutions of pHs 2, 7 and 9, and DSC thermal properties were evaluated. In-vitro drug release from the film coated prednisolone tablets were evaluated in 0.1N HCl, water and phosphate buffer 8.0 as dissolution media. Films showed ESC in the order A>D>E>B>C; D>C>A>E>B and A>D>C>B>E in acidic, neutral and alkali media respectively. EMS was in the order B>E>A>D>C; with slight shift in the melting temperatures. In-vitro release at 240 min varied from 78 to 117 % (E>D>C>A>B); 19 to 60 % (D>B>C>E>A) and 49 to 60 % (B>A>C>D>E) in 0.1N HCl, water and PBS respectively. Cross-linking improved the stability and swelling of films. The in-vitro release in alkaline medium suggests their usefulness for controlled drug delivery. New pH-responsive polymers, with improved physicochemical properties for coating prednisolone tablets were developed.

Folic acid-poly(N-isopropylacrylamide-maltodextrin) nanohydrogels as novel thermo-/pH-responsive polymer for resveratrol breast cancer targeted therapy

BackgroundThe long-term sequelae and serious side effects of conventional breast cancer chemotherapy due to ubiquitous biodistribution and systemic toxicity remain the main obstacle to success in clinic. Recent anticancer research rely on tailoring smart carriers to overcome these drawbacks. In this regard, numerous stimuli-responsive polymers have been assembled and successfully employed as smart carriers various chemotherpeutic agents due to their intrinsic tumor targeting properties. Among which, poly(N-isopropylacrylamide (PNIPAM) has gained increasing attention being amenable to various chemical modifications for tuning its intrinsic thermoresponsivity or endowing additional stimulus responsiveness. This work aims to develop PNIPAM-maltodextrin nanohydrogels (PNIPAM-MD NGs) decorated with folic acid (FA) as smart breast cancer-targeted stimuli-responsive delivery system to the natural polyphenol resveratrol (RSV) suffering from low bioavailaibity. ResultsPNIPAM-MD was synthesized by graft copolymerization, characterized and evaluated for its modulated stimuli-responsivity. The PNIPAM-based copolymer was coupled with FA, the breast cancer active targeting ligand. The FA-PNIPAM-MD NGs core was loaded RSV, then subjected to in vitro and in vivo evaluation. Results showed that the developed RSV-loaded FA-PNIPAM-MD (F3) NGs displayed dual thermo- and pH-responsivities, high drug-loading capacity (8.31 wt%,) and excellent physical and serum stability. The targeted formula F3 exhibited enhanced in vitro anti-breast cancer potency as evident by 7.4 folds reduction in the IC50 of free RSV and significant MCF-7 cellular uptake. In breast cancer-bearing mice, F3 suppressed the tumor growth, lowered VEGF-1 and Ki-67 expression levels, and induced apoptosis via upregulating caspase-3. ConclusionOverall, the PNIPAM-MD NGs as well as its FA-decorated breast cancer-targted NGs could serve as promising smart nanocarrier for efficient RSV brest cancer delivery. It could be safely deduced that the assembled FA-PNIPAM-MD F3 NGs enabled sequestering the therapeutic cargo (RSV) in normal tissue and released it in tumor site, thus guarding against its rapid metabolism and maximizing its accumulation in the cancer tissue as evidenced by the remarkable tumor growth suppression noticed in the targeted RSV/FA-PNIPAM-MD F3 NGs-treated mice compared to that in the free RSV-treated group. Hence, The fabricated nanohydrogels may be further employed for smart delivery of various anti-breast cancer agents.

Synthesis and characterization of pH-responsive ferrogels comprising sulfamethazine-based polymer and magnetic nanoparticles for sensing ammonia gas

Ferrogels have been widely used in soft actuators and as carriers in drug delivery systems owing to their responsiveness to magnetic stimulus. Herein, a novel ferrogel that exhibits chemically modulated magnetism is synthesized, by dispersing magnetic nanoparticles (MNPs) in a hydrogel produced from a pH-responsive sulfamethazine-based polymer during polymerization and cross-linking. The MNPs exhibit dynamic rotations or oscillations in the rheological matrix under alternating current (AC) magnetic fields. The AC magnetization behavior of the incorporated MNPs is modulated by the swelling of the hydrogel in response to changes in pH over the range of 7–12. The ferrogels with larger swelling ratios exhibit enhanced Brownian relaxation during AC magnetization. Based on the pH response of the AC magnetization, the detection of ammonia gas is investigated using the ferrogel as a sensing label, and the sensitivity of 5.3 × 10−6 mol/L or lower has been achieved. Therefore, the as-prepared ferrogel is suitable for use as a sensing label in applications such as the sensing of ammonia emitted from human skin for health monitoring.

Glycopolymer Decorated pH-Dependent Ratiometric Fluorescent Probe Based on Förster Resonance Energy Transfer for the Detection of Cancer Cells.

Development of fluorescent imaging probes is an important topic of research for the early diagnosis of cancer. Based on the difference between the cellular environment of tumor cells and normal cells, several "smart" fluorescent probes have been developed. In this work, a glycopolymer functionalized Förster resonance energy transfer (FRET) based fluorescent sensor is developed, which can monitor the pH change in cellular system. One-pot sequential reversible addition-fragmentation chain transfer (RAFT)polymerization technique is employed to synthesize fluorescent active triblock glycopolymer that can undergo FRET change on the variation of pH. A FRET pair, fluorescein o-acrylate (FA) and 7-amino-4-methylcoumarin (AMC) is linked via a pH-responsive polymer poly [2-(diisopropylamino)ethyl methacrylate] (PDPAEMA), which can undergo reversible swelling/deswelling under acidic/neutral condition. The presence of glycopolymer segment provides stability, water solubility, and specificity toward cancer cells. The cellular FRET experiments on cancer cells (MDA MB 231) and normal cells (3T3 fibroblast cells) demonstrate that the material is capable of distinguishing cells as a function of pH change.

Au Nanorods Coated with pH-Responsive Polymers for Photothermal Therapy Against Multidrug-Resistant Bacteria

Au Nanorods Coated with pH-Responsive Polymers for Photothermal Therapy Against Multidrug-Resistant Bacteria

PH-activated nanoplatform for visualized photodynamic and ferroptosis synergistic therapy of tumors.

To overcome drug resistance and improve precision theranostics for hepatocellular carcinoma (HCC), a nanoplatform with an "off/on" function for multimodality imaging (near-infrared-II (NIR-II) fluorescence imaging, magnetic resonance imaging (MRI), and photoacoustic imaging) and synergistic therapy (photodynamic therapy and ferroptosis) activated by an acidic pH in the tumor microenvironment is proposed. Although many photosensitizers with photodynamic effects have been reported, very few of them have outstanding photodynamic effect and high stability with response to endogenous stimuli capable of NIR-II imaging. Herein, a new amphiphilic photosensitizer SR780 derived from croconaine dye, was developed with satisfactory photodynamic effects and pH-responsive NIR-II imaging. Interestingly, it was deactivated by coordination with Fe3+ (SR780@Fe) and activated during their release under mild acidic condition. Ferroptosis can generate hydroxyl free radical and lipid peroxide, which aggravate the oxidative stress of tumor cells and mediate their death while depleting glutathione (GSH) to enhance photodynamic effect. In situ pH-activatable theranostic nanoplatform, SR780@Fe-PAE-GP, was thus developed by loading SR780@Fe with pH-responsive polymers, modified by a glypican-3 (GPC-3) receptor-targeting peptide. The synergistic antitumor effects were confirmed both in vitro and in vivo, and the tumor inhibition rate of the SR780@Fe-PAE-GP+L treatment group reached 98%.

Low-Cost Nonreversible Electronic-Free Wireless pH Sensor for Spoilage Detection in Packaged Meat Products.

Contamination of meat with pathogenic microorganisms can cause severe illnesses and food waste, which has significant negative impacts on both general health and the economy. In many cases, the expiration date is not a good indicator of meat freshness as there is a high risk of contamination during handling throughout the supply chain. Many biomarkers, including color, odor, pH, temperature, and volatile compounds, are used to determine spoilage. Among these, pH presents a simple and effective biomarker directly linked to the overgrowth of bacteria and degradation of the meat tissue. Low-cost methods for wireless pH monitoring are crucial in detecting spoilage on a large commercial scale. Existing technologies are often limited to short-range detection, with the use of batteries and different electronic components that increases both the manufacturing complexity and cost of the final device. To address these shortcomings, we have developed a cost-effective wireless pH sensor, which uses passive resonant frequency (RF) sensing, combined with a pH-responsive polymer that can be placed within packaged meat products and provide a remote assessment of the risk of microbial spoilage throughout the supply chain. The sensor tag consists of a sensing resonator coated with a pH-sensitive material and a passivated reference resonator operating in a differential frequency configuration. Upon exposure to elevated pH levels >6.8, the coating on the sensing resonator dissolves, which in turn results in a distinct change in the resonant frequency with respect to the reference resonator. Systematic theoretical and experimental results at different pH levels demonstrated that a 20% shift in resonant frequency demarcates the point for spoilage detection. As a proof of concept, the performance of the sensor in remotely detecting the risk of food spoilage was validated in packaged poultry over 10 days. The sensor fabrication process takes advantage of recent developments in the scalable manufacturing of flexible, low-cost devices, including selective laser etching of metalized plastic films and doctor-blade coating of stimuli-responsive polymer films. Furthermore, the biocompatibility of all the materials used in the sensor was confirmed with human intestinal cells (HCT-8 cells).

PH-Responsive non-antibiotic polymer prodrugs eradicate intracellular infection by killing bacteria and regulating immune response

Intracellular bacterial infections pose enormous challenges to food safety and public health. Antibiotic-based polymer prodrugs have been used to treat intracellular bacterial infection. However, the overuse of antibiotics may lead to the emergence of antibiotic resistance. In this work, we aimed to develop antibiotic-free pH-responsive polymeric prodrugs to combat intracellular S. aureus infection. Amphiphilic poly(ethylene glycol)-b-poly[(3-phenylprop-2-ene-1,1-diyl)bis(oxy)bis(enthane-2,1-diyl)diacrylate] (PEG-b-PCAE) was obtained by radical polymerization and they could self-assemble to form micelles. PEG-b-PCAE micelles could uptake by macrophage. Upon exposure to the acidic phagolysosome, PEG-b-PCAE micelles could release cinnamaldehyde (CA) through hydrolysis of the acetal linkage. PEG-b-PCAE could kill intracellular bacteria by damaging the bacterial membrane. Furthermore, PEG-b-PCAE micelles could generate reactive oxygen species (ROS) in macrophages and subsequently activate immune system to clear bacteria by inducing macrophages differentiation to M1 phenotype. PEG-b-PCAE micelles could accelerate the wound healing process of the S. aureus-infected model in vivo. It is anticipated that multifunctional antibiotic-free PEG-b-PCAE micelles with intrinsic antibacterial activities hold promise for improved outcomes in intracellular S. aureus infections.

PH-Responsive Polyelectrolyte Coatings that Enable Catheter-Mediated Transfer of DNA to the Arterial Wall in Short and Clinically Relevant Inflation Times.

We report the design and characterization of pH-responsive polymer coatings that enable catheter balloon-mediated transfer of DNA to arterial tissue in short, clinically relevant inflation times. Our approach exploits the pH-dependent ionization of poly(acrylic acid) (PAA) to promote disassembly and release of plasmid DNA from polyelectrolyte multilayers. We characterized the contact transfer of multilayers composed of PAA, plasmid DNA, and linear poly(ethyleneimine) (LPEI) identified as promising in prior studies on the delivery of DNA to arterial tissue. In contrast to thinner films evaluated previously, we found thicker coatings composed of 32 repeating (LPEI/PAA/LPEI/DNA)x tetralayers to swell substantially in physiologically relevant media (in PBS; pH = 7.4). In some cases, these coatings also disintegrated or delaminated rapidly from their underlying substrates, suggesting the potential for enhanced balloon-mediated transfer. We developed a technically straightforward agarose gel-based hole-insertion model to characterize factors (inflation time, lumen size, etc.) that influence contact transfer of DNA when film-coated balloons are inflated into contact with soft surfaces. Those studies and the results of in vivo experiments using small animal (rat) and large animal (pig) models of peripheral arterial injury revealed catheters coated with these materials to promote robust contact transfer of DNA to soft hydrogel surfaces and the luminal surfaces of arterial tissue using inflation times as short as 30 s. These short inflation times are relevant in the context of clinical vascular interventions in peripheral arteries. Additional studies demonstrated that contact transfer of DNA using these short times can promote subsequent dissemination and transport of DNA to the medial tissue layer, suggesting the potential for use in therapeutically relevant applications of balloon-mediated gene transfer.

XA pH-Responsive and Colitis-Targeted Nanoparticle Loaded with Shikonin for the Oral Treatment of Inflammatory Bowel Disease in Mice.

Epidemiology shows that more than 6.8 million people in the world are influenced by inflammatory bowel disease (IBD) each year. IBD is a refractory inflammatory disease, and the disease mainly affects the colon. Shikonin (SK) was originally extracted from traditional Chinese medicine "Zicao" (with an English name Lithospermum erythrorhizon) and found to inhibit inflammation, regulate immunity, and be involved in healing wounds. Herein, we used chitosan (CS), hyaluronic acid (HA), and pH-responsive polymer Eudragits S100 (ES100) to design SK-loaded ES100/HA/CS nanoparticles (SK@SAC) as an oral delivery system to treat the colitis mice. Particle size of SK@SAC was 190.3 nm and drug loading efficiency was 6.6%. SAC nanoparticles accumulated in RAW264.7 macrophages and exhibited colitis-targeted ability by increasing the local drug concentration as well as reducing nonspecific distribution after oral gavage. In TNBS-induced IBD mice, SK@SAC treatment had significant therapeutic effects, regulated of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10 and TGF-β), and also inhibited COX-2 and iNOS activity. SK@SAC also increased tight junction protein ZO-1 and occludin to some extent. These promising results showed that this novel oral SK-loaded nanoparticle drug delivery system for targeted treatment provides a new strategy for the management of IBD.

PH-Responsive Hyperbranched Polymer Nanoparticles to Combat Intracellular Infection by Disrupting Bacterial Wall and Regulating Macrophage Polarization.

Intracellular bacterial infections pose a serious threat to public health. Macrophages are a heterogeneous population of immune cells that play a vital role in intracellular bacterial infection. However, bacteria that survive inside macrophages could subvert the cell signaling and eventually reduce the antimicrobial activity of macrophages. Herein, dual pH-responsive polymer (poly[(3-phenylprop-2-ene-1,1-diyl)bis(oxy)bis(enthane-2,1-diyl)diacrylate-co-N-aminoethylpiperazine] (PCA)) nanoparticles were developed to clear intracellular bacteria by activating macrophages and destructing bacterial walls. The presence of acid-labile acetal linkages and tertiary amine groups in the polymer's backbone endow hyperbranched PCA dual pH-response activity that shows acid-induced positive charge increase and cinnamaldehyde release properties. The biodegraded PCA nanoparticles could significantly inhibit the growth of bacteria by damaging the bacterial walls. Meanwhile, PCA nanoparticles could uptake by macrophages, generate reactive oxygen species (ROS), and remodel the immune response by upregulating M1 polarization, leading to the reinforced antimicrobial capacity. Furthermore, PCA nanoparticles could promote bacteria-infected wound healing in vivo. Therefore, these dual pH-responsive PCA nanoparticles enabling bacteria-killing and macrophage activation provide a novel outlook for treating intracellular infection.

Self-healing and anticorrosion coatings based on responsive polymers with metal coordination bonds

Coatings containing corrosion inhibitors are effective materials for hindering corrosion of metals and alloys structures. However, shortcomings of these coatings include an uncontrolled leaching of inhibitors and susceptibility to mechanical damages, which lead to a shortened anticorrosion property. To overcome these issues, we prepare a new smart coating with the abilities of releasing selectively corrosion inhibitors and repairing autonomously mechanical damages. This dual-function is imparted by a pH-responsive polymer containing a corrosion inhibitor which coordinates cerium ions. Upon corrosion, the polymer releases the corrosion inhibitor and cerium which then forms insoluble cerium oxides or cerium hydroxides on cathodic sites. The corrosion rate of aluminum alloys coated with the polymer conjugate complex is ∼ 31 times lower than for the coating of the polymer conjugate that is not complexed. Self-healing after mechanical damage is enabled by the metal–ligand coordination bond between cerium ions and conjugated 8-hydroxyquinoline (8HQ), leading to a restauration of ∼ 98 % of the anticorrosion properties.

Gamma irradiation-induced pH-responsive poly(methyl methacrylate- acrylic acid-divinyl benzene) hybrid polymer particles for dye treatment

ABSTRACT The environmentally friendly method is used to fabricate spherical poly(methyl methacrylate-methyl acrylate-divinylbenzene) (P(MMA-MA-DVB)) hybrid particles by gamma irradiation-induced suspension polymerization without an initiator. The MMA: MA: DVB of 60: 20: 20 was used to encapsulate 10 wt% oleic coated-magnetic nanoparticles using ultrasonication for monomer droplet preparation. A stable suspension with approximately 90% monomer conversion was produced using 5 kGy gamma-ray to initiate the polymerization. A large quantity of submicrometer-sized free polymer particles as a by-product was formed in an aqueous medium where the radicals were generated by gamma irradiation of water. However, the number of free polymer particles decreased with the decrease in monomer droplet size. The obtained particles were hydrolyzed to form P(MMA-AA-DVB) particles presenting a negative surface charge (> −30 mV) in an alkaline condition. It was found that the prepared particles presented dye adsorption efficiency as the methylene blue (MB) concentration reduced with adsorption time. The MB adsorption efficiency also increased with pH due to the presence of PAA as a pH-responsive material. Moreover, the hybrid polymer particles were easily separated by the application of an external magnet. Therefore, the fabricated pH-responsive hybrid polymer particles would be served as an alternative dye adsorbent for wastewater treatment.

Poly(N-isopropylacrylamide)-based temperature- and pH-responsive polymer materials for application in biomedical fields

Poly(N-isopropylacrylamide)-based temperature- and pH-responsive polymer materials for application in biomedical fields

Stimuli-responsive polymer-based aqueous two-phase extraction of analytes in complex matrices

• Stimuli-responsive polymer-based ATPSs are effective green extraction techniques. • Temperature and pH are the common stimuli used in these ATPSs. • These ATPSs use less aggressive conditions during the extraction of analytes. • The stimuli-responsive polymers in the ATPS are recyclable after the extraction process. The use of aqueous two-phase systems (ATPSs) during extraction of analytes from complex matrices is increasingly gaining popularity. This can be attributed to the fact that these systems are generally simple, fast and environmentally friendly. The success of aqueous two-phase extraction largely depends on the good choice of materials to be used. The availability of smart materials such as stimuli-responsive polymers has facilitated the development of effective ATPSs for the extraction of analytes from complex matrices. This paper explores the utilisation of stimuli-responsive polymers during these biphasic systems. The stimuli-responsive polymers that are in common use in ATPSs include thermo-responsive and pH-responsive polymers. Other researchers used dual-stimuli-responsive ATPSs, which involve a combination of a thermo-responsive polymer and a pH-responsive polymer, during extraction of analytes from complex matrices. These biphasic systems composed of thermo-responsive and pH-responsive polymers are discussed in detail in this paper. In addition, this review explores the challenges associated with the use of stimuli-responsive polymers in ATPSs as well as the future prospects.