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     

Thermo‐responsive injectable hydrogel system based on poly(N‐isopropylacrylamide‐co‐vinylphosphonic acid). I. Biomineralization and protein delivery

To achieve the injectable hydrogel system in order to improve bone regeneration by locally delivering a protein drug including bone morphogenetic proteins, thermo‐responsive injectable hydrogels composed of N‐isopropylacrylamide (NIPAAm) and vinyl phosphonic acid (VPAc) were prepared. The P(NIPAAm‐co‐VPAc) hydrogels were also biomineralized by urea‐mediation method to create functional polymer hydrogels that deliver the protein drug and mimic the bone extracellular matrix. The loosely cross‐linked P(NIPAAm‐co‐VPAc) hydrogels were pliable and fluid‐like at room temperature and could be injected through a small‐diameter aperture. The lower critical solution temperature (LCST) of P(NIPAAm‐co‐VPAc) hydrogel was influenced by the monomer ratio of NIPAAm/VPAc and the hydrogel with a 96/4 molar ratio of NIPAAm/VPAc exhibited an LCST of ～34.5°C. Water content was influenced by temperature, NIPAAm/VPAc monomer ratio, and biomineralization; however, all hydrogels maintained more than about 77% of the water content even at 37°C. In a cytotoxicity study, the P(NIPAAm‐co‐VPAc) and biomineralized P(NIPAAm‐co‐VPAc) hydrogels did not significantly affect cell viability. The loading content of bovine serum albumin in hydrogel, which was used as a model drug, gradually increased with the amount of VPAc in the hydrogel owing to the ionic interaction between VPAc groups and BSA molecules. In addition, the release behavior of BSA from the P(NIPAAm‐co‐VPAc) hydrogels was mainly influenced by the drug loading content, water content, and biomineralization of the hydrogels. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and characterization of a novel thermosensitive hydrogel based on chitosan and gelatin blends

In this study, a novel injectable in situ gelling thermosensitive hydrogel system based on chitosan and gelatin blends was designed and investigated. The addition of gelatin provides the correct buffering and other physicochemical conditions including control of hydrophobic interactions and hydrogen bonding, which are necessary to retain chitosan in solution at neutral pH near 4°C and furthermore to allow gel formation upon heating to body temperature. The chitosan/gelatin hydrogels were studied by FTIR, swelling, and rheological analysis. The rheological analysis evidenced the endothermic gelation of chitosan/gelatin solutions, which indicated their gelation temperatures and reflected the effect of gelatin concentration on the thermosensitive properties of gels. The morphology of this system was examined with laser scanning confocal microscopy and scanning electron microscopy. The images indicated that the gels were quite heterogeneous and porous. The investigation of these gels as vehicles for delivering bovine serum albumin as a model drug of protein showed that the system could sustain the release of the protein drug. These results show that chitosan/gelatin solutions can form gels rapidly at body temperature and have promising perspective for their use in local and sustained delivery of protein drug. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Application of minimally invasive injectable conductive hydrogels as stimulating scaffolds for myocardial tissue engineering

So far, several methods for myocardial tissue engineering have been developed to regenerate myocardium and even create contractile heart muscles. Among these approaches, hydrogel based methods have attracted much attention due to their ability to mimic the architecture of native extracellular matrix. Injectable hydrogels are a specific class of hydrogels which can be formed in situ by physical and/or chemical crosslinking. Generally, using these hydrogels is more advantageous because they are minimally (less) invasive in comparison with open surgery. Moreover, with respect to the fact that ‘myocardium is a conductive tissue’, utilization of conductive polymers for myocardial tissue engineering has demonstrated promising results. Both the injectable hydrogels and conductive polymers have some merits and demerits, but studies show that using a combination of them has prominently enhanced regeneration of the myocardium. In this review, the focus is on injectable hydrogels, conductive polymers and injectable conductive hydrogels for myocardial tissue engineering. © 2018 Society of Chemical Industry     

Chemical synthesis of biomimetic hydrogels for tissue engineering

Owing to their high water content, porous structure, biocompatibility and tissue‐like viscoelasticity, hydrogels have become attractive and promising biomaterials for use in drug delivery, three‐dimensional cell culture and tissue engineering applications. Various chemical approaches have been developed for hydrogel synthesis using monomers or polymers carrying reactive functional groups. For in vivo tissue repair and in vitro cell culture purposes, it is desirable that the crosslinking reactions occur under mild conditions, do not interfere with biological processes and proceed at high yield with exceptional selectivity. Additionally, the crosslinking reaction should allow straightforward incorporation of bioactive motifs or signaling molecules, at the same time providing tunability of the hydrogel microstructure, mechanical properties and degradation rates. In this review, we discuss various chemical approaches applied to the synthesis of complex hydrogel networks, highlighting recent developments from our group. The discovery of new chemistries and novel materials fabrication methods will lead to the development of the next generation of biomimetic hydrogels with complex structures and diverse functionalities. These materials will likely facilitate the construction of engineered tissue models that may bridge the gap between two‐dimensional experiments and animal studies, providing preliminary insight prior to in vivo assessments. © 2017 Society of Chemical Industry     

pH‐thermoreversible hydrogels. I. Synthesis and swelling behaviors of the (N‐isopropylacrylamide‐co‐acrylamide‐co‐2‐hydroxyethyl methacrylate) copolymeric hydrogels

A series of pH‐thermoreversible hydrogels that exhibited volume phase transition was synthesized by various molar ratios of N‐isopropylacrylamide (NIPAAm), acrylamide (AAm), and 2‐hydroxyethyl methacrylate (HEMA). The influence of environmental conditions such as temperature and pH value on the swelling behavior of these copolymeric gels was investigated. Results showed that the hydrogels exhibited different equilibrium swelling ratios in different pH solutions. Amide groups could be hydrolyzed to form negatively charged carboxylate ion groups in their hydrophilic polymeric network in response to an external pH variation. The pH sensitivities of these gels also depended on the AAm content in the copolymeric gels; thus the greater the AAm content, the higher the pH sensitivity. These hydrogels, based on a temperature‐sensitive hydrogel, demonstrated a significant change of equilibrium swelling in aqueous media between a highly solvated, swollen gel state and a dehydrated network response to small variations of temperature. pH‐thermoreversible hydrogels were used for a study of the release of a model drug, caffeine, with changes in temperature. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 221–231, 1999     

Thermoreversible hydrogel. XVII. Investigation of the drug release behavior for [N‐isopropylacrylamide‐co‐trimethyl acrylamidopropyl ammonium iodide‐co‐3‐dimethyl (methacryloyloxyethyl) ammonium propane sulfonate] copolymeric hydrogels

A series of copolymeric hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm), trimethyl acrylamidopropyl ammonium iodide (TMAAI), and 3‐dimethyl (methacryloyloxyethyl) ammonium propane sulfonate (DMAPS). Results showed that the swelling ratios of these copolymeric hydrogels increased with an increase of TMAAI content. The drug release behavior of the ionic thermosensitive hydrogels related to their ionicity and drug types. Results indicated that the release ratio of caffeine in the hydrogels was not affected by the ionicity of hydrogels, but increased with increasing of the swelling ratio. The anionic solute (phenol red) strongly interacted with cationic hydrogel (very large K_d), so the phenol red release ratio in cationic gels was very low. On the other hand, CV was adsorbed only on the skin layer of the cationic hydrogel because of the charge repulsion, and released rapidly. Therefore the release ratio was highest for cationic hydrogel to cationic drug. In addition, the partition coefficients (K_d) and the drug delivery behavior of the present gels were also investigated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1592–1598, 2002     

Biodegradable polymers exhibiting temperature-responsive sol–gel transition as injectable biomedical materials

Injectable biodegradable copolymer hydrogels, which exhibit temperature-responsive sol-to-gel transition, have recently drawn much attention as promising biomedical materials such as drug delivery, cell implantation, and tissue engineering. These injectable hydrogels can be implanted in the human body with minimal surgical invasion. Temperature-responsive gelling copolymers usually possess block- and/or branched architectures and amphiphilicity with a delicate hydrophobic/hydrophilic balance. Poly(ethylene glycol) (PEG) has typically been used as hydrophilic segments due to its biocompatibility and temperature-dependent dehydration nature. Aliphatic polyesters such as polylactide, poly(lactide-co-glycolide), poly(ε-caprolactone), and their modified copolymers have been used as hydrophobic segments based on their biodegradability and biocompatibility. Copolymers of PEG with other hydrophobic polymers such as polypeptides, polydepsipeptides have also been recently reported as injectable hydrogels. In this review, brief history and recent advances in injectable biodegradable polymer hydrogels are summarized especially focusing on the relationship between polymer architecture and their gelation properties. Moreover, the applications of these injectable polymer gels for biomedical use such as drug delivery and tissue engineering are also described.     

Preparation and properties of a novel thermosensitive <Emphasis Type="Italic">N</Emphasis>-trimethyl chitosan hydrogel

A novel injectable thermosensitive hydrogel system composed of N-trimethyl chitosan chloride (TMC) and β-glycerophosphate (β-GP), coded as TMC/β-GP, was designed. The morphology and rheological behavior of hydrogels were characterized by scanning electron microscopy and rheometer, respectively. Their swelling properties were carefully studied. The results revealed that the TMC/β-GP system was liquid with low viscosity at low temperature, which allowed it to be an ideal injectable material for biomedical applications. It was interesting that the system kept in liquid status for a long time near 4 °C and transformed rapidly to gel status within 1 min upon heating to 37 °C. The hydrogel could be dissolved at acid pH, while it absorbed water at neutral and basic conditions. The release of BSA from TMC/β-GP gels was slow at neutral pH. The TMC/β-GP hydrogel is a promising vehicle for the drug release, tissue repairing and regeneration.     

Structure and properties of polysaccharide nanocrystal-doped supramolecular hydrogels based on Cyclodextrin inclusion

Polysaccharide nanocrystals, such as the rod-like whiskers of cellulose and chitin, and platelet-like starch nanocrystals, were for the first time incorporated into supramolecular hydrogels based on cyclodextrin/polymer inclusion in order to enhance mechanical strength and regulate drug release behavior. The structures and properties of the resultant nanocomposite hydrogels were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and rheological testing. As expected, the elastic modulus of the nanocomposite hydrogels climbed, owing to the reinforcing function of the polysaccharide nanocrystals. The modulus of the cellulose whisker-doped hydrogel was 50 times higher than that of the native hydrogel. Furthermore, the presence of polysaccharide nanocrystals increased the stability of the hydrogel framework and inhibited the diffusion of bovine serum albumin, which served as a model protein drug in the nanocomposite hydrogels and showed prominent sustained release profiles. Importantly, the incorporation of polysaccharide nanocrystals did not show additional cytotoxicity as comparison with the native hydrogel. In addition, the inherited shear-thinning property of the nanocomposite hydrogels contributed to their potential as injectable biomaterials.     

Formation of silk fibroin hydrogel and evaluation of its drug release profile

Silk hydrogels are interesting materials to be used as matrix in controlled drug delivery devices. However, methods to accelerate fibroin gelation and allow the drug incorporation during the hydrogel preparation are needed in literature. In this article we report the preparation of silk fibroin hydrogels with addition of several contents of ethanol, used to accelerate fibroin gelation kinetics, and we also evaluate the potential of these hydrogels to be used as matrices for drug delivery. Chemical and conformational properties did not change despite the amount of ethanol incorporated in the hydrogel. Hydrogels containing diclofenac sodium dissolved in ethanol showed a faster initial release of the drug than hydrogels with the drug dissolved in water but equilibrium was reached later. This indicates a more sustained drug delivery from hydrogels in which the model drug was dissolved in ethanol. Fibroin hydrogels confirm their promising use as biopolymeric matrices for controlled drug release. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41802.     

Synthesis,Characterization, and drug release study of acrylamide‐co‐itaconic acid based smart hydrogel

A new kind of pH and temperature responsive poly(acrylamide‐co‐itaconic acid) hydrogel was prepared by free radical polymerization using ammonium persulfate as initiator and different comonomer ratios. The hydrogels were characterized in terms of chemical composition, swelling‐deswelling behavior, morphology, crystallographic behavior, and drug release properties. All the hydrogels showed high swelling ability in aqueous solutions, the maximum being at pH 7. Swelling decreased on either side of pH 7 (i.e., both in acidic and alkaline region) and increased with increase in temperature. The hydrogel with 10 mol% itaconic acid (IA) absorbed maximum water among the copolymer gels. The cellular structures of the hydrogels were clearly revealed by microscopic analysis and SEM pictures. Swelling of the gels in water followed non‐Fickian type of diffusion principle. The hydrogel was proved to be a controlled release vehicle, for example in drug delivery by using its smart properties. The hydrogel with 10 mol% IA also absorbed maximum amount of drug (ascorbic acid) under study. Incorporation of drug in hydrogel matrix was established from XRD peak analysis. POLYM. ENG. SCI., 55:113–122, 2015. © 2014 Society of Plastics Engineers     

Effect of drug loading on the properties of temperature‐responsive polyester–poly(ethylene glycol)–polyester hydrogels

Hydrogels that can undergo gelation upon injection in vivo are promising systems for the site‐specific delivery of drugs. In particular, some thermo‐responsive gels require no chemical additives but simply gel in response to a change from a lower temperature to physiological temperature (37 °C). The gelation mechanism does not involve covalent bonds, and it is possible that incorporation of drugs into the hydrogel could disrupt gelation. We investigated the incorporation of drugs into thermo‐responsive hydrogels based on poly(?‐caprolactone‐co‐lactide)‐block‐poly(ethylene glycol)‐block‐poly(?‐caprolactone‐co‐lactide) (PCLA–PEG–PCLA). Significant differences in properties and in the response to incorporation of the anti‐inflammatory drug celecoxib (CXB) were observed as the PEG block length was varied from 1500 to 3000 g mol^?1. Linear viscoelastic moduli of a PCLA–PEG–PCLA hydrogel containing a 2000 g mol^?1 PEG block were least affected by the incorporation of CXB and this gel also exhibited the slowest release of CXB, so the incorporation of phenylbutazone, methotrexate, ibuprofen, diclofenac and etodolac was also investigated for this hydrogel. Different drugs resulted in varying degrees of syneresis of the hydrogels, suggesting that they interact with the polymer networks in different ways. In addition, the drugs had varying effects on the viscoelastic and compressive moduli of the gels. The results showed that the effects of drug loading on the properties of thermo‐responsive hydrogels can be substantial and depend on the drug. For applications such as intra‐articular drug delivery, in which the mechanical properties of the hydrogel are important, these effects should thus be studied on a case‐by‐case basis. © 2019 Society of Chemical Industry     

Thermosensitive chitosan hydrogel for implantable drug delivery: Blending PVA to mitigate body response and promote bioavailability

Thermosensitive hydrogels promise to be the injectable implants for long-term controlled drug release; however, body response to the implanted hydrogels and its unpredictable impacts on drug release complicates their applications. In the present study, hydrophilic polymer poly(vinyl alcohol) (PVA) was blended into the thermosensitive hydrogel composed of chitosan and glycerophosphate to mitigate the body responses and promote the drug bioavailability. The effects of PVA on the surface properties of the hydrogel were evaluated by zeta-potential, water contact angle, and cell attachment. Body responses were explored by histological examination via subcutaneously implanting the hydrogels into Sprague-Dawley rats. Drug release in vivo and bioavailability were determined with cyclosporine A (CsA) employed as the model drug. The results showed that, on one hand, the presence of PVA improved the surface hydrophilicity of the hydrogel and inhibited the cell attachment on the hydrogel, which alleviated the further cell infiltration and tissue integration in body; and on the other hand, blending of PVA led to the more rapid gel formation and more compact network, which resisted the dehydration and survived the hydrogel from cell division. These advantages benefited the controlled release and absorption of CsA, and contributed to the higher drug bioavailability. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Electroresponsive and spinnable hydrogels from xanthan gum and gelatin enhanced by Fe3+ ions coordination

Polyelectrolyte hydrogels with spinnability and electroresponsive were prepared from xanthan gum (XG) and gelatin. Oscillatory rheological measurements were utilized to explore mechanical properties and thermal stability of the resultant XG-Gelatin5 hydrogels. The XG-Gelatin5 hydrogels possessed higher strength and larger critical strain than these of the XG hydrogels, demonstrating existence of synergistic interactions. The XG-Gelatin5 hydrogels were stable in temperature range of 20–60°C, and gradually release drug with controlled manner in neutral and acid medium at 37°C. The self-recoverable and thixotropic XG-Gelatin5 hydrogels were extruded to form hydrogel fibers, and the dried hydrogel fibers rapidly bend towards cathode under applied voltage. Long hydrogel fibers were harvested with enhancement by Fe³⁺ ions, and were weaved and braided to obtain hydrogel fiber constructs. The XG-Gelatin5 hydrogel fibers with electroresponsive and controlled drug release possess potential applications in biomaterials, tissue engineering, and drug carrier fields.     

Photopolymerized hydrogel composites from poly(ethylene glycol) and hydroxyapatite for controlled protein delivery in vitro

The incorporation of hard particles into soft hydrogels can improve the mechanical properties and provide necessary bioactivity to the hydrogels for desired biomedical applications. Hydrogel composites containing hydroxyapatite (HA) are promising materials for orthopedic applications. In this study, injectable poly(ethylene glycol) (PEG) hydrogel precursor solutions containing HA particles and model protein bovine serum albumin (BSA) were synthesized in situ by photopolymerization. In vitro BSA release properties from the hydrogel composites containing various amounts of HA were investigated and discussed. Fourier transform infrared spectroscopy and scanning electron microscopy were employed to investigate the interaction between HA and the hydrogel network and the morphology of the hydrogel composites. It is found that PEG hydrogel composites containing HA sustained the release of BSA for at least 5 days and the presence of HA slowed down BSA release. Photopolymerized hydrogel composites containing HA may find potential use as a drug delivery matrix for orthopedic tissue engineering. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Controlled release of Montelukast Sodium from pH-sensitive injectable hydrogels

pH sensitive hydrogels showed excellent drug release properties, with promise for other biomedical applications. Also, the impact of molecular weight (MW) and degree of deacetylation (DDA) of chitosan on the fabricated chitosan/poly (vinyl alcohol) (3:1 mol ratio) hydrogel with selective silane crosslinker amount was evaluated for controlled drug delivery. The FTIR spectroscopy confirmed the incorporated components and the developed interactions among the polymer chains. The hydrogel characteristics were expressed by their responsive behaviour in different environments (water, ionic media and pH). The hydrogel sample (CH1000) having chitosan with higher MW and DDA exhibited more thermal stability and bacterial growth inhibition against E.coli. All hydrogels exhibited maximum swelling at basic and neutral pH and less swelling was observed in acidic media. For drug release analysis performed in simulated gastric fluid, hydrogel showed controlled drug release in 2 h but it was more than 10%, consequently cannot be used for oral purpose. In simulated intestinal fluid, hydrogels exhibited more than 80% release within 90 min. This characteristic phenomenon at neutral pH empowered hydrogel appropriate towards injectable and targeted controlled release of applicable drug. It was concluded that the prepared hydrogel can be administered directly into the venous circulation through syringe and can be used with better results for biomedical applications.     

Production of chitosan PVA PCL hydrogels to bind heparin and induce angiogenesis

New blood vessel formation is an essential part of wound healing to provide cells with the nutrients and oxygen for their survival. Many nonhealing ulcers fail to heal because of poor blood supply and skin grafts will also fail to take on poorly vascularized wound beds. There is a real need for proangiogenic biomaterials to assist wound healing. In vivo heparin binds proangiogenic growth factors and helps regulate new blood vessel formation, hence heparin containing biomaterials are attractive. To achieve a hydrogel with high heparin binding capacity a composite of chitosan, poly(vinyl alcohol) (PVA) and polycaprolactone (PCL) was produced. Chitosan is a biodegradable natural polymer with great potential for biomedical applications due to its biocompatibility, high charge density and nontoxicity. PVA is biocompatible and nontoxic with good chemical stability, film-forming ability, and high hydrophilicity. PCL has physicochemical and mechanical properties comparable to those of the biological tissues and due its hydrophilic nature helps in the sustained release of drugs. Accordingly in this study we explored a range of PCL concentrations from 4% to 16% added to hydrogels composed of chitosan and PVA. Heparin was blended into the polymer mixture and the nanoporous structure was created by freeze-drying the PCL hydrogel. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR) and XPS confirmed the presence of sulfur on the surface of the hydrogels. Their porous morphology was investigated by scanning electron microscope (SEM). The Chick Chorionic Allantoic Membrane (CAM) assay was used to study the angiogenic potential of these materials and histology (H&E and Goldner trochome) was used to confirm the presence of new blood vessels inside the hydrogels. We report that the addition of 8% PCL to the hydrogels gave porous structures containing heparin, which significantly increased new blood vessel formation into the hydrogels. These hydrogels offer a new approach to biomaterials, which could be added to wounds to improve vascularization.     

Preparation of ‘click’ hydrogels from polyaspartamide derivatives

Lately, copper‐assisted azide–alkyne cycloaddition (CuAAC) has become a very interesting tool for synthesizing biocompatible polymer‐based materials such as hydrogels or microgels, which can be used as biomaterials for tissue engineering and drug delivery. Novel poly(2‐hydroxyethyl aspartamide)s (PHEAs) functionalized with pendent acetylene or azide groups were prepared from polysuccinimide, which is the thermal polycondensation product of aspartic acid, through successful ring‐opening reactions using propargylamine, 1‐azido‐2‐aminoethane and ethanolamine. The composition of the prepared copolymers was analyzed using ¹H NMR spectroscopy. Clickable PHEA derivatives were crosslinked by mixing together in water with a catalyst system of Cu(I) and N, N, N′, N′, N″‐pentamethyldiethylenetriamine, a type of Huisgen's 1,3‐dipolar azide‐alkyne cycloaddition. The reaction of the polymers resulted in a chemoselective coupling between alkynyl and azido functional groups with multiple formation of triazole crosslinks to give hydrogels. The triazole linkages in the hydrogels are highly stable and may also play a role in swelling behavior. PHEA‐based hydrogels were also obtained by the crosslinking of azide‐ or alkyne‐modified PHEA with a small‐molecule crosslinker. The hydrogels prepared using these two methods were characterized by their degree of swelling and the morphology of the hydrogels was confirmed using scanning electron microscopy. The approach we describe here presents a promising alternative to common chemical hydrogel preparation techniques, and these hydrogels seem to possess structures having potential for a variety of industrial and biomedical applications. © 2012 Society of Chemical Industry     

A novel temperature and pH dual‐responsive hybrid hydrogel with polyhedral oligomeric silsesquioxane as crosslinker: synthesis,characterization and drug release properties

Octavinyl polyhedral oligomeric silsesquioxane (OVPS) is used as the crosslinker instead of N,N′‐methylenebisacrylamide (BIS) to copolymerize with 2‐(dimethylamino)ethyl methacrylate (DMAEMA) or DMAEMA and N‐isopropylacrylamide (NIPAM) to prepare hybrid hydrogels: P(OVPS‐co‐DMAEMA) and P(OVPS‐co‐DMAEMA‐co‐NIPAM). The prepared hydrogels are transparent and show dual response to temperature and pH. The hydrogels were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, dynamic mechanical analysis and tensile tests. Their mechanical properties, swelling ratio, deswelling and reswelling behaviors as well as drug release properties were investigated. The results indicate that OVPS can be incorporated into polymer networks in proportion to feed ratios. The P(OVPS‐co‐DMAEMA) hydrogel exhibits more homogeneous interior structure, higher swelling ratio and faster response than the conventional hydrogel prepared with BIS. Moreover, the incorporation of OVPS enhances the compression and tensile properties of the hydrogels. The feed ratios of OVPS and NIPAM have a great effect on volume phase transition temperature, thermal sensitivity, swelling behavior, mechanical properties and drug release properties of the hybrid hydrogels. The prepared dual‐responsive OVPS‐containing hydrogels are expected to be used as biomedical materials in drug release and tissue engineering. © 2014 Society of Chemical Industry