Smart carboxymethylchitosan hydrogels that have thermo‐ and pH‐responsive properties

Thermo‐responsive poly(N‐isopropylacrylamide) (poly(NIPAAm)) and pH‐responsive poly(N,N′‐diethylaminoethyl methacrylate) (poly(DEAEMA)) polymers were grafted to carboxymethylchitosan (CMC) via radical polymerization to form highly water swellable hydrogels with dual responsive properties. Ratios of CMC, NIPAAm to DEAEMA used in the reactions were finely adjusted such that the thermo and pH responsiveness of the hydrogels was retained. Scanning electron microscopy (SEM) indicated the formation of an internal porous structure for the swollen CMC hydrogels upon incorporation of poly(NIPAAm) and poly(DEAEMA). Effect of temperature and pH changes on water swelling properties of the hydrogels was investigated. It was found that the water swelling of the hydrogels was enhanced when the solution pH was under basic conditions (pH 11) or the temperature was below its lower critical solution temperature (LCST). These responsive properties can be used to regulate releasing rate of an entrapped drug from the hydrogels, a model drug, indomethacin was used to demonstrate the release. These smart and nontoxic CMC‐based hydrogels show great potential for use in controlled drug release applications with controllable on‐off switch properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41505.     

Intracellular pH‐sensitive dextran‐based micelles as efficient drug delivery platforms

As drug delivery systems, stimuli‐responsive polymer micelles hold great potential in cancer chemotherapeutics to improve therapeutic efficiency and eliminate organism adverse effects. Here, pH‐sensitive polymeric micelles based on dextran‐g‐benzimidazole were designed and used for intracellular anticancer drug delivery. The anticancer drug doxorubicin (DOX) was effectively loaded into the micelles via hydrophobic interactions. In vitro release studies demonstrated that the release of loaded DOX was greater and faster under acid conditions such as in carcinomatous areas (pH < 6.8) than in physiological conditions (pH 7.4). MTT assays and flow cytometric analyses showed that DOX‐loaded micelles had higher cellular proliferation inhibition towards HeLa and HepG2 cells than pH‐insensitive controls. These pH‐sensitive micelles with significant efficiency for intracellular drug release will be beneficial to the future of in vivo biomedical applications. © 2014 Society of Chemical Industry     

pH‐ and temperature‐responsive IPN hydrogels based on soy protein and poly(N‐isopropylacrylamide‐co‐sodium acrylate)

pH‐ and temperature‐responsive interpenetrating polymer network (IPN) hydrogels based on soy protein and poly(N‐isopropylacrylamide‐co‐sodium acrylate) were successfully prepared. The structure and properties of the hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, and thermogravimetric analyzer. The equilibrium and dynamic swelling/deswelling behaviors and the drug release properties of the hydrogels responding to pH and/or temperature were also studied in detail. The hydrogels have the porous honeycomb structures, good miscibility and thermal stability, and good pH‐ and temperature‐responsivity. The volume phase transition temperature of the hydrogels is ca. 40°C. Changing the soy protein or crosslinker content could be used to control the swelling behavior and water retention, and the hydrogels have the fastest deswelling rate in pH 1.2 buffer solutions at 45°C. Bovine serum albumin release from the hydrogels has the good pH and temperature dependence. The results show that the proposed IPN hydrogels may have potential applications in the field of biomedical materials such as in drug delivery systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39781.     

Synthesis and characterization of novel pH‐responsive poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) hydrogels for drug delivery

In this study, N‐allylsuccinamic acid (NASA) was synthesized in a single step with a yield of 85%. Carboxylic acid containing NASA was characterized through Fourier transform infrared (FTIR) radiation and ¹H‐NMR and ¹³C‐NMR analysis, and then it was used for synthesis of poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) [p(HEMA‐co‐NASA)] hydrogels. The structure of the obtained pH‐responsive p(HEMA‐co‐NASA) hydrogels were characterized with FTIR spectroscopy and scanning electron microscopy analysis, and their swelling characterization was carried out under different drug‐release conditions. In the application step of the study, the hydrogels were used for the in vitro release of vitamin B12 and Rhodamine 6G, which were selected as model drugs. We determined that the hydrogels used as a drug‐delivery matrix could release the drug they had absorbed under different release conditions (phosphate‐buffered saline, 0.9% NaCl, and pH 1.2) at high rates for time periods of up to 24 h. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39660.     

Temperature/pH dual responsive microgels of crosslinked poly(N‐vinylcaprolactam‐co‐undecenoic acid) as biocompatible materials for controlled release of doxorubicin

Undecenoic acid functionalized thermo/pH responsive microgels, poly(N‐vinylcaprolactam‐co‐undecenoic acid) [poly(VCL‐co‐UA)], were synthesized by precipitation emulsion copolymerization. The microgels exhibit reversible thermo/pH responsive phase transition behavior, which can be tuned by varying the monomer feed ratio. The lower critical solution temperatures (LCSTs) of the materials are close to body temperature. As a result, when temperatures rise above ca. 37°C, a rapid thermal gelation process occurs, accompanied by a phase transition, resulting in expulsion of encapsulated compound. In vitro experiment evaluated its applicability as a drug carrier for controlled release of an anticancer agent (doxorubicin) and showed that the drug encapsulation efficiency (EE), releasing rate, and kinetics are dependent on the temperature and pH value as expected. Minimal cytotoxicity of the microgels was observed by a cytotoxicity assay using 3T3 fibroblast cells. Our finding suggests that the poly(VCL‐co‐UA) based microgels may be considered a promising candidate for temperature or pH‐controlled delivery of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41146.     

Strategies To Design and Synthesize Polymer-Based Stimuli-Responsive Drug-Delivery Nanosystems

The emergence and development of nanomedicine have alleviated problems existing in traditional chemotherapy drugs, such as short lifetime, concomitant side effects, and weak tumor-targeting capability. Nevertheless, the further applications of drug-loaded nanocarriers are still limited by their premature leakage, weak targeting capability, and insufficient intracellular release. In past decades, various nanocarriers, including gold nanoparticles, porous silica nanoparticles, carbon-based nanoparticles, micelles, liposomes, and polymer–drug conjugates, have been intensively investigated for tumor therapy. Among these, polymer-based nanocarriers have attracted more attention due to their biocompatibilities and capability of being modified for stimuli-responsive drug release. In this review, three popular strategies to design and synthesize polymer-based stimuli-responsive nanocarriers are discussed. The discussion goes from stimuli-responsive polymers with responsive backbones or modified by responsive functional groups for drug encapsulation and release to polymer–drug conjugates with responsive covalent linkages. In particular, due to the facile synthetic processes and mild reaction conditions for crosslinked structures, the latest progress in responsive crosslinked structures is emphasized. Finally, future perspectives for these nanomaterials are given, which are expected to provide inspiration for researchers to design more effective and safer tumor-killing nanomedicines.     

Photoresponsive nanogels synthesized using spiropyrane‐modified pullulan as potential drug carriers

Reversible light‐responsive nanogels were constructed from an amphiphilic spiropyrane‐modified pullulan (SpP). The polymer was synthesized by modifying a biodegradable pullulan with carboxyl‐containing spiropyrane (Sp) molecules. The SpP structure was confirmed by the appearance of a carbonyl signal in the FT‐IR and ¹H NMR spectra. The nanogels can be controlled by photostimulation, which results in the reversible structural transformation of the hydrophobic Sp to the hydrophilic merocyanine. The physical properties of the nanogels were confirmed to change dramatically after being irradiated with different wavelengths of light. Drug delivery tests showed that the model drug pyrene was completely captured by the nanogels and then released from the SpP nanogels in a light‐dependent manner. This study provides an alternative approach to constructing light‐responsive nanocarriers with excellent biocompatibility for drug uptake and release. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40288.     

Quinone propionic acid‐based redox‐triggered polymer nanoparticles for drug delivery: Computational analysis and in vitro evaluation

Redox‐responsive polymers with pendant quinone propionic acid groups as a redox trigger were optimized by computational modeling to prepare efficient redox‐triggered polymer nanoparticles (NPs) for drug delivery. Lipophilicities at complete reduction of redox‐responsive polymers (<5000 Da) constructed with adipic acid and glutaric acid were remarkably reduced to range from ?6.29 to ?0.39 compared with nonreduced state (18.87–32.46), suggesting substantial polymer solubility reversal in water. Based on this hypothesis, redox‐responsive NPs were prepared from the synthesized polymers with paclitaxel as model cancer drug. The average size of paclitaxel‐loaded NPs was 249.8 nm and their reconstitutions were stable over eight weeks. In vitro drug release profiles demonstrated the NPs to release >80% of paclitaxel over 24 h at a simulated redox‐state compared with 26.5 to 41.2% release from the control. Cell viability studies revealed that the polymer was nontoxic and the NPs could release paclitaxel to suppress breast cancer cell growth. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40461.     

Study of pH/temperature dual stimuli‐responsive nanogels with interpenetrating polymer network structure

Nanogels with interpenetrating polymer network (IPN) structure based on poly(N‐isopropylacrylamide) (PNIPAM) and poly(acrylic acid) (PAA) were synthesized by in situ polymerization of acrylic acid and N, N′‐methylenebisacrylamide within the PNIPAM nanogels. Their IPN structure was confirmed using transmission electron microscopy after staining by uranyl acetate. The temperature‐ or pH‐dependent hydrodynamic diameters measured using dynamic laser light scattering show that the IPN nanogels have pH and temperature dual stimuli‐responsive properties. As compared to previously reported pH/temperature dual stimuli‐responsive nanogels, these IPN nanogels have the advantage of less mutual interference between the temperature‐responsive and pH‐responsive components, which is beneficial for their applications in controlled drug release and sensors. The temperature‐ and pH‐triggered volume phase transition mechanisms of the IPN nanogels were tested by probing the microenvironment change of their PNIPAM and PAA chains upon phase transition using infrared (IR) absorption spectra measured at different pH values and IR difference spectra obtained by subtracting the IR spectrum obtained before temperature‐induced phase transition from that obtained after phase transition. Copyright © 2012 Society of Chemical Industry     

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

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.     

Dual‐stimuli‐responsive polymer‐coated mesoporous silica nanoparticles used for controlled drug delivery

In this article, a temperature‐ and pH‐responsive delivery system based on block‐copolymer‐capped mesoporous silica nanoparticles (MSNs) is presented. A poly[2‐(diethylamino)ethyl methacrylate)] (PDEAEMA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAM) shell on MSNs was obtained through the surface‐initiated atom transfer radical polymerization. The block copolymer PDEAEMA‐b‐PNIPAM showed both temperature‐ and pH‐responsive properties. The release of the loaded model molecules from PDEAEMA‐b‐PNIPAM‐coated MSNs could be controlled by changes in the temperature or pH value of the medium. The as‐desired drug‐delivery carrier may be applied to biological systems in the future. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42395.     

Temperature,pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for controlled release

Temperature, pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for drug delivery and release are designed. The well‐defined tetrablock copolymer poly(polyethylene glycol methacrylate)–poly[2‐(dimethylamino) ethyl methacrylate]–poly(N‐isopropylacrylamide)–poly(methylacrylic acid) (PPEGMA‐PDMAEMA‐PNIPAM‐PMAA) is synthesized via atom transfer radical polymerization, click chemistry, and esterolysis reaction. The tetrablock copolymer self‐assembles into noncrosslinked micelles in acidic aqueous solution. The core‐crosslinked micelles, shell‐crosslinked micelles, and shell–core dilayer‐crosslinked micelles are prepared via quaternization reaction or carbodiimide chemistry reaction. The crosslinked micelles are used as drug carriers to load doxorubicin (DOX), and the drug encapsulation efficiency with 20% feed ratio reached 59.2%, 73.1%, and 86.1%, respectively. The cumulative release rate of DOX is accelerated by single or combined stimulations. The MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay verifies that the inner‐layer crosslinked micelles show excellent cytocompatibility, and DOX‐loaded micelles exhibit significantly higher inhibition for HepG2 cell proliferation. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46714.     

Encapsulation of diclofenac sodium with acidic copolymer hydrogels based on PEG/poly(N‐isopropylacrylamide‐co‐2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) semi‐interpenetrating network using in situ loading technique

A pH‐ and temperature‐responsive semi‐interpenetrating copolymer PEG6000/poly(NIPA‐co‐AMPS) (PEG/AMPS‐co‐NIPA SIPN), for short PEG SIPN, was made by ammonium persulfate‐initiated suspension copolymerization of N‐isopropylacrylamide, 2‐acrylamido‐2‐methylpropanesulphonic acid, and N,N′‐methylene‐bis‐acrylamide (MBAA; crosslinker) in the presence of PEG6000. The PEG SIPN copolymer matrices containing nanostructures made in the high‐temperature copolymerization resulted in channels for PEG and facile migration of drugs. In drug encapsulation or drug‐loading process, one can easily ignore or pay less attention to the interaction between a drug and its encapsulation materials; however, the ignored interactions may induce problems in drug properties or the release behavior in use. Sodium diclofenac (DFNa) precipitates as the carboxylic acid form in an acidic environment, and it is challenging to encapsulate sodium diclofenac in such an acidic matrix without precipitation of the sparingly soluble acid form of DFNa on the surface of the polymer substrate. To avoid bulky precipitation in drug loading, an in situ loading technique was developed for producing gel spheres with DFNa uniformly distributed in the polymer matrix. The technique is based on fast polymerization of spherical droplets of a pregel solution in which the drug is dissolved. Diffusion‐loading prodrugs were made in comparison with in situ loading prodrugs in thermal, release kinetics, and release behavior. Drug release profiles (in pH 7.4 phosphate buffer) show that the new drug loading technique gives controlled release during a period of about 7 days at 37°C. By contrast, gel spheres loaded with sodium diclofenac using the conventional diffusion technique produced almost total release of the drug within about 24 h. The thermal stability of sodium diclofenac, the PEG/AMPS‐co‐NIPA SIPN, and the prodrugs made with the SIPN and sodium diclofenac was studied. A near zero‐order release kinetics was found in the in vitro release of sodium diclofenac with in situ loading PEG SIPN prodrug. We have, for the first time, studied sodium diclofenac release behavior from the PEG SIPN hydrogel systems. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Properties of pH‐dependent tertiary amine‐based gels as potential drug delivery matrices

The rheological and morphological properties and in vitro theophylline release of tertiary amine‐based microgels were evaluated. The testing of such a formulation through in vitro diffusion experiments revealed that the release of theophylline from the microgels was pH‐dependent and differs significantly with respect to a nonresponsive gel like scleroglucan (Scl). The microgels were obtained from 2‐(diethyl amino) ethylmethacrylate (DEA) in the presence of a bifunctional crosslinker at pH 8–9. As the resulting microgels are pH‐responsive and an increase in viscosity from high to low pH range is exhibited, the in vitro release of theophylline as model drug was studied at different pHs of both the matrix and the receptor medium. The release behaviors of PDEA‐based microgels were compared to nonresponsive natural gel Scl, studied previously. For microgels, diverse release patterns were found at different acidity conditions. This observation seems to be related to complex diffusion phenomena and the different gel structure obtained for samples prepared at dissimilar pH. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 4035–4040, 2007     

Saccharide‐based nanocarriers for targeted therapeutic and diagnostic applications

Many therapeutic and diagnostic agents suffer from short circulation times or poor selectivity resulting in the need for frequent drug administration and adverse side‐effects. On this basis, selective nanocarriers have been used to address most of the drawbacks via the encapsulation or conjugation of therapeutic and diagnostic agents to allow the targeted release of cargo to diseased sites or tumours, while maintaining low levels of cytotoxicity. Saccharides, which can be classified as monosaccharides, disaccharides and oligo/polysaccharides, have demonstrated great potential in the construction of nanocarriers, as well as the targeted guidance of the nanocarriers to diseased tissues. The fabrication of nanocarriers from natural materials such as polysaccharides affords biodegradability and biocompatibility, and in some instances confers targeting capabilities. The most recent progress in saccharide‐based targeted nanocarriers fabricated via facile one‐pot routes or complex two‐pot synthetic routes is reviewed here, with a particular focus on the high efficiency and flexibility of the one‐pot approach. In addition, inspired by the self‐assembly processes involving saccharides that occur in living organisms, particular emphasis is placed on disease‐targeting nanocarriers that are constructed from or modified by saccharides. © 2018 Society of Chemical Industry     

Thermal and pH dual‐responsive hydrogels based on semi‐interpenetrating network of poly(N‐isopropylacrylamide) and collagen nanofibrils

Hydrogels with environment‐sensitive properties have great potential applications in the controlled drug release field. In this paper, hybrid hydrogels with semi‐interpenetrating polymer networks (semi‐IPNs), composed of poly(N‐isopropylacrylamide) (PNIPAM) as the thermo‐sensitive component by in situ polymerization and self‐assembled collagen nanofibrils as the pH‐sensitive framework, were prepared for controlled release of methyl violet as a model drug. From Fourier transform infrared spectroscopy and scanning electron microscopy, it was indicated that the crosslinking of PNIPAM in the presence of collagen nanofibrils led to the formation of semi‐IPNs with homogeneous porous structure, and the semi‐IPNs showed improved thermal stability and elastic properties compared with the native collagen as determined using differential scanning calorimetry and rheologic measurements. Furthermore, the semi‐IPNs possessed swelling behaviors quite different from those of neat collagen or PNIPAM hydrogel under various pH values and temperatures. Correspondingly, as expected, the drug release behavior in vitro for semi‐IPNs performed variously compared with that for single‐component semi‐IPNs, which revealed the tunable performance of semi‐IPNs for release ability. Finally the thermo‐ and pH‐responsive mechanism of the semi‐IPNs was illuminated to provide guidance for the application of the thermo‐ and pH‐sensitive collagen‐based hybrid hydrogels in controlled drug delivery systems. © 2019 Society of Chemical Industry     

Poly(acrylic acid‐co‐acrylamide‐co‐2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid)‐grafted nanocellulose/poly(vinyl alcohol) composite for the in vitro gastrointestinal release of amoxicillin

Superabsorbent polymer composites (SAPCs) are very promising and versatile materials for biomedical applications. This study concentrates on the development of novel cellulose‐based SAPC, Poly(acrylic acid‐co‐acrylamide‐co?2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid)‐grafted nanocellulose/poly(vinyl alcohol) composite, P(AA‐co‐AAm‐co‐AMPS)‐g‐NC/PVA, as a potential drug delivery vehicle. Amoxicillin was selected as a model drug, which is used for the treatment of Helicobacter pylori induced peptic and duodenal ulcers. P(AA‐co‐AAm‐co‐AMPS)‐g‐NC/PVA was synthesized by graft copolymerization reaction, and FTIR, XRD, SEM, and DLS analyses were performed for its characterization. Equilibrium swelling studies were conducted to evaluate the stimuli‐response behavior of the SAPC and found that equilibrium swelling was dependent on pH, contact time, temperature, ionic strength, concentration of crosslinker and PVA. Maximum drug encapsulation efficiency was found out by using different concentrations of amoxicillin. Drug release studies were carried out at simulated gastric and intestinal fluids and the release % was observed as maximum in intestinal fluids within 4 h. The drug release kinetics was investigated using Peppas' potential equation and follows non‐Fickian mechanism at pH 7.4. Thus, the drug release experiments indicate that P(AA‐co‐AAm‐co‐AMPS)‐g‐NC/PVA would be a fascinating vehicle for the in vitro administration of amoxicillin into the gastrointestinal tract. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40699.     

pH‐responsive core crosslinked polycarbonate micelles via thiol‐acrylate Michael addition reaction

A facile method for the construction of pH‐responsive core crosslinked micelles (CCLMs) based on polycarbonate was developed. Biodegradable amphiphilic block copolymer monomethoxy poly(ethylene glycol)‐b‐Poly(AC) (mPEG‐b‐poly(AC)) with pendant acrylate group was synthesized by means of ring opening polymerization of acryloyl carbonate (AC). Then CCLMs were obtained via thiol‐acrylate Michael addition reaction between the pendant acrylate group in the hydrophobic block and the crosslinker 1,6‐hexanedithiol. DLS results showed that the CCLMs prepared from mPEG‐b‐poly(AC)₂₅ were more stable than uncrosslinked micelles (UCLMs) upon dilution by 10‐fold DMF. Model drug Coumarin 102 was then encapsulated into the micelles. The pH‐responsive release of coumarin 102 from the CCLMs was demonstrated by fluorescence spectroscopy. The core crosslinked polycarbonate micelles have a potential as efficient intracellular smart drug delivery platforms. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44421.     

Photo‐cross‐linked biodegradable thermo‐ and pH‐responsive hydrogels for controlled drug release

A new strategy was developed to prepare thermo‐ and pH‐sensitive hydrogels by the crosslinking of poly(N‐isopropylacrylamide) with a biodegradable crosslinker derived from poly(L ‐glutamic acid). Hydrogels were fabricated by exposing aqueous solutions of precursor containing photoinitiator to UV light irradiation. The swelling behaviors of hydrogels at different temperatures, pHs, and ionic strengths were examined. The hydrogels shrank under acidic condition or at temperature above their collapse temperature and would swell in neutral or basic media or at lower temperature. These processes were reversible as the pH or temperature changed. All hydrogels exhibited no weight loss in the simulated gastric fluid but degraded rapidly in the simulated intestinal condition. Bovine serum albumin were used as a model protein drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and temperatures. The pH and temperature dependent release behaviors indicated the promising application of these materials as stimuli‐responsive drug delivery vehicles. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Dual pH‐ and thermal‐responsive nanocomposite hydrogels for controllable delivery of hydrophobic drug baicalein

Hydrogels have been widely used as mild biomaterials due to their bio‐affinity, high drug loading capability and controllable release profiles. However, hydrogel‐based carriers are greatly limited for the delivery of hydrophobic payloads due to the lack of hydrophobic binding sites. Herein, nano‐liposome micelles were embedded in semi‐interpenetrating poly[(N‐isopropylacrylamide)‐co‐chitosan] (PNIPAAm‐co‐CS) and poly[(N‐isopropylacrylamide)‐co‐(sodium alginate)] (PNIPAAm‐co‐SA) hydrogels which were responsive to both temperature and pH, thereby establishing tunable nanocomposite hydrogel delivery systems. Nano‐micelles formed via the self‐assembly of phospholipid could serve as the link between hydrophobic drug and hydrophilic hydrogel due to their special amphiphilic structure. The results of transmission and scanning electron microscopies and infrared spectroscopy showed that the porous hydrogels were successfully fabricated and the liposomes encapsulated with baicalein could be well contained in the network. In addition, the experimental results of response release in vitro revealed that the smart hydrogels showed different degree of sensitiveness under different pH and temperature stimuli. The results of the study demonstrate that combining PNIPAAm‐co‐SA and PNIPAAm‐co‐CS hydrogels with liposomes encapsulated with hydrophobic drugs is a feasible method for hydrophobic drug delivery and have potential application prospects in the medical field. © 2018 Society of Chemical Industry