pH-sensitive Swelling Properties Research Articles

Accelerating ESD-induced gastric ulcer healing using a pH-responsive polyurethane/small intestinal submucosa hydrogel delivered by endoscopic catheter.

Endoscopic submucosal dissection (ESD) is the standard treatment for early-stage gastric cancer, but the large post-operative ulcers caused by ESD often lead to serious side effects. Post-ESD mucosal repair materials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a polyurethane/small intestinal submucosa (PU/SIS) hydrogel and investigated its efficacy for accelerating ESD-induced ulcer healing in a canine model. PU/SIS hydrogel possessed great biocompatibility and distinctive pH-sensitive swelling properties and protected GES-1 cells from acid attack through forming a dense film in acidic conditions in vitro. Besides, PU/SIS gels present a strong bio-adhesion to gastric tissues under acidic conditions, thus ensuring the retention time of PU/SIS gels in vivo. In a canine model, PU/SIS hydrogel was easily delivered via endoscopy and adhered to the ulcer sites. PU/SIS hydrogel accelerated gastric ulcer healing at an early stage with more epithelium regeneration and slight inflammation. Our findings reveal PU/SIS hydrogel is a promising and attractive candidate for ESD-induced ulcer repair.

Biobased pH-responsive and self-healing hydrogels prepared from O-carboxymethyl chitosan and a 3-dimensional dynamer as cartilage engineering scaffold

Novel dynamic hydrogels were prepared from O-carboxymethyl chitosan (CMCS) and a water soluble dynamer Dy via crosslinking by imine bond formation using an environmentally friendly method. Dy was synthesized by reaction of Benzene-1,3,5-tricarbaldehyde with Jeffamine. The resulting soft hydrogels exhibit a porous and interconnected morphology, storage modulus up to 1400 Pa, and excellent pH-sensitive swelling properties. The swelling ratio is relatively low at acidic pH due to electrostatic attraction, and becomes exceptionally high up to 7000 % at pH 8 due to electrostatic repulsion. Moreover, hydrogels present outstanding self-healing properties as evidenced by closure of split pieces and rheological measurements. This study opens up a new horizon in the preparation of dynamic hydrogels with great potential for applications in drug delivery, wound dressing, and in particular in tissue engineering as the hydrogels present excellent cytocompatibility.

In situ synthesis of poly (γ- glutamic acid)/alginate/AgNP composite microspheres with antibacterial and hemostatic properties

In the present work, a poly(γ-glutamic acid)/alginate/silver nanoparticle (PGA/Alg/AgNP) composite microsphere with excellent antibacterial and hemostatic properties was prepared by the in situ UV reduction and emulsion internal gelation method, and its potential application for antibacterial hemostatic dressing was explored. Well dispersed AgNPs were in situ synthesized by a UV reduction method with alginate as stabilizer and reductant. The AgNPs showed excellent antibacterial activities against both gram-negative and gram-positive bacteria. Additionally, the AgNPs prepared by the in-situ UV reduction exhibited better biocompatibility and antibacterial effects than those prepared by the conventional chemical reduction method. PGA/Alg/AgNP composite microspheres were then prepared with the AgNPs by an emulsion internal gelation method. Such microspheres were found to be a porous and hollow network with pH-sensitive swelling properties and excellent hemostatic performance, indicating its application potentials as an advanced antibacterial hemostatic material.

Preparation and properties of novel hydrogel based on chitosan modified by poly(amidoamine) dendrimer

Currently, chitosan (CTS) or chitosan derivatives hydrogels are applied in different fields, such as biological materials, medical materials and hygiene materials. In this study, novel chitosan hydrogels were successfully prepared by chitosan and poly(amidoamine) (PAMAM) dendrimer with glutaraldehyde serving as a cross-linking agent. Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC) were performed to characterize PAMAM. The structure and morphology of hydrogels were characterized by FTIR, thermo gravimetry analysis (TGA), and scanning electron microscopy (SEM). The swelling properties of the hydrogels were investigated in solutions of pH 1.0 and 7.4. The hydrogels showed good swelling capacities and pH-sensitive swelling properties. Besides, the antibacterial activities of the hydrogels against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) were tested by optical density. Compared with the pure chitosan hydrogel, their antibacterial activities were significantly improved with the increase in the blending ratio of PAMAM. And with the increase in cross-linking agent and concentration of CTS, the antibacterial activities increased firstly and then slightly decreased. The hydrogel was expected to be a novel antibacterial material.

Preparation of dual temperature/pH-sensitive polyampholyte gels and investigation of their protein adsorption behaviors

Dual temperature/pH-sensitive polyampholyte gels were developed for use as adsorbents and carriers that deal with organic electrolytes such as proteins. NIPA-co-DMAPAA-co-AA gels were prepared by copolymerizing N-isopropylacrylamide (NIPA) as a thermosensitive component with N,N-dimethylaminopropylacrylamide (DMAPAA) as a weakly-basic cation-comonomer, acrylic acid (AA) as a weakly-acidic anion-comonomer, and N,N′-methylenebisacrylamide (MBAA) as a cross-linker, and their thermosensitive and pH-sensitive swelling properties and protein adsorption properties were investigated. The gel adsorbed bovine serum albumin (BSA) applied as a model protein at pH values in the range of 4.5–10 and 25°C as a result of the electrostatic interactions. In addition, the pre-adsorbed BSA was well desorbed from the gel at pH values less than 4 or greater than 11. The pH-sensitivity of the adsorption is found to be based on the protonation of amino groups in DMAPAA and dissociation of carboxyl groups of AA. The BSA adsorption was investigated as a function of MBAA concentration and temperature, and was discussed in terms of the difference in the sizes of the BSA molecule and gel network.

Design and in vitro evaluation of formulations with pH and transit time controlled sigmoidal release profile for colon-specific delivery

The primary objective of the study was to develop a pH and transit time controlled sigmoidal release polymeric matrix for colon-specific delivery of indomethacin. Tablet matrices were prepared using a combination of hydrophilic polymers (polycarbophil or carbopol) having pH-sensitive swelling properties with hydrophobic polymer ethyl cellulose. The prepared matrices were characterized for physical properties and in vitro release kinetics. The presence of ethyl cellulose in a hydrophilic polymer matrix resulted in a sigmoidal in vitro drug release pattern with negligible-to-very low drug release in the initial phase (0–6 h) followed by controlled release for 14–16 h. The retardation in initial release can be attributed to the presence of ethyl cellulose that reduced swelling of hydrophilic polymer(s), while in the later portion, polymer relaxation at alkaline pH due to the ionization of acrylic acid units on carbopol and polycarbophil resulted in enhanced drug release. Thus, a sigmoidal release pattern was obtained that could be ideal for colonic delivery of indomethacin in the potential treatment of colon cancer.

Design and in vitro evaluation of formulations with pH and transit time controlled sigmoidal release profile for colon-specific delivery

The primary objective of the study was to develop a pH and transit time controlled sigmoidal release polymeric matrix for colon-specific delivery of indomethacin. Tablet matrices were prepared using a combination of hydrophilic polymers (polycarbophil or carbopol) having pH sensitive swelling properties with hydrophobic polymer ethyl cellulose. The prepared matrices were characterized for physical properties and in vitro release kinetics. The presence of ethyl cellulose in a hydrophilic polymer matrix resulted in a sigmoidal in vitro drug release pattern with negligible to very low drug release in the initial phase (0–6 h) followed by controlled release for 14–16 h. The retardation in initial release can be attributed to the presence of ethyl cellulose that reduced swelling of hydrophilic polymer(s) while in the later portion, polymer relaxation at alkaline pH due to the ionization of acrylic acid units on carbopol and polycarbophil resulted in enhanced drug release. Thus, a sigmoidal release pattern was obtained that could be ideal for colonic delivery of indomethacin in the potential treatment of colon cancer.

Synthesis and characterization of pH-sensitive microgels by derivatization of npa-based reactive copolymers

There has been an increased interest in recent years in evaluating the swelling behaviour of pH-sensitive polymer gels, since they are potentially useful in a wide range of applications such as biomedical materials, biosensors, and the removal of contaminants from sewage waste. Nanosized NPA-based copolymers have been synthesized and chemically modified in order to introduce ionizable pendant groups with different p K a into the macromolecular networks. These modification reactions were controlled by 1H NMR and UV spectroscopy. SEM micrographs of modified microgels show samples to be monodisperse spheres. The pH-sensitivity of the final microgels has been studied by the determination of the hydrodynamic diameters by QELS as a function of pH. All the systems underwent a swelling transition near the estimated apparent p K a according to the introduced pendant groups. The pH-sensitive equilibrium swelling behaviour of microgels derivatized with 4-methylpyridyne has been studied as a function of ionic strength and copolymer composition. There are some facts related to the ionizable pendant groups that influence and determine the pH-responsive swelling behaviour of microgels, such as the p K a, content, accesibility of these groups, and ionic strength of external solution. According to this, a simple and versatile derivatization strategy has been employed to design intelligent microgels with specific pH-sensitive swelling properties.

Synthesis and characterization of methacrylic derivatives of 5-amino salicylic acid with pH-sensitive swelling properties

The purpose of this study is to develop novel colon-specific drug delivery systems with pH-sensitive swelling and drug release properties. Methacrylic-type polymeric prodrugs with different content levels of 5-amino salicylic acid (5-ASA) were synthesized by free radical copolymerization of metacrylic acid (MAA), polyethylene glycol monomethacrylate (PEGMA), and a methacrylic derivative of 5-ASA (methacryloyloxyethyl 5-amino salicylate [MOES]). The copolymers were characterized, and the drug content of the copolymers was determined. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). The swelling and hydrolytic behavior of the copolymers was dependent on the content of MAA groups and caused a decrease in gel swelling in SGF or an increase in gel swelling in SIF. Drug release studies showed that increasing content of MAA in the copolymer enhances the hydrolysis in SIF but has no effect in SGF. The results suggest that hydrogen-bonded complexes are formed between MAA and PEG pendant groups and that these pH-sensitive systems could be useful for preparation of a controlled-release formulation of 5-ASA.

Synthesis and characterization of methacrylic derivatives of 5-amino salicylic acid with pH-sensitive swelling properties.

The purpose of this study is to develop novel colon-specific drug delivery systems with pH-sensitive swelling and drug release properties. Methacrylic-type polymeric prodrugs with different content levels of 5-amino salicylic acid (5-ASA) were synthesized by free radical copolymerization of metacrylic acid (MAA), polyethylene glycol monomethacrylate (PEGMA), and a methacrylic derivative of 5-ASA (methacryloyloxyethyl 5-amino salicylate [MOES]). The copolymers were characterized, and the drug content of the copolymers was determined. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). The swelling and hydrolytic behavior of the copolymers was dependent on the content of MAA groups and caused a decrease in gel swelling in SGF or an increase in gel swelling in SIF. Drug release studies showed that increasing content of MAA in the copolymer enhances the hydrolysis in SIF but has no effect in SGF. The results suggest that hydrogen-bonded complexes are formed between MAA and PEG pendant groups and that these pH-sensitive systems could be useful for preparation of a controlled-release formulation of 5-ASA.