pH-sensitive Interpenetrating Polymer Network Research Articles

Carbohydrate polymer based pH-sensitive IPN microgels: Synthesis, characterization and drug release characteristics

pH-sensitive interpenetrating polymer network (IPN) microgels of chitosan (CS) and guargum-g-poly((2-dimethylamino)ethylmethacrylate) (GG-g-PDMAEMA) were developed by emulsion crosslinking method using glutaraldehyde as a crosslinker. In this regard, primarily guargum (GG) is grafted with (2-dimethylamino)ethylmethacrylate (DMAEMA) followed by blended with CS to prepare various microgel formulations. These microgels were treated as responsive drug carriers for an anticancer agent, 5-fluorouracil (5-FU). The maximum % encapsulation efficiency was found to be 81. Fourier transform infrared analysis was used to investigate the formation of graft copolymer (GG-g-PDMAEMA), chemical structure of microgels as well as the chemical interactions of drug molecules with the polymer matrix. The surface morphological studies and average particle size were examined by scanning electron microscopy. The average size of microgels is 130 ± 20 μm. Thermal behavior and molecular distribution of 5-FU within the polymer matrix were confirmed from thermogravimetric analysis and X-ray diffraction experiments. The pH-sensitive swelling behavior of IPN microgels was investigated in different pH solutions. To study the release profile of 5-FU, in vitro release profiles were performed in both pH 1.2 and 7.4. The release kinetics showed pH- dependent drug release and IPN microgels exhibited an excellent controlled release pattern for 5-FU over a period of more than 24 h. The release mechanism was analyzed by evaluating the release data using different empirical equations.

In vitro and in vivo assessment of novel pH-sensitive interpenetrating polymer networks of a graft copolymer for gastro-protective delivery of ketoprofen

Novel pH-sensitive IPN microbeads exhibited drug release in response to changing pH and reduced side effects of ketoprofenin vivo.

Tailored-interpenetrating polymer network beads of κ-carrageenan and sodium carboxymethyl cellulose for controlled drug delivery

Interpenetrating polymer network (IPN) beads of κ-Carrageenan and sodium carboxymethyl cellulose (SCMC) containing Ibuprofen were prepared by water-in-water emulsion gelation process using AlCl3 as a cross-linking agent. The impact of different formulation variables like polymer ratio, gelation time, concentration of crosslinker on physico-chemical parameters and in-vitro drug release were studied. The IPN beads were investigated through Scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis. The prepared beads were slightly rough, folded spherical in shape and reflected improved drug encapsulation efficiency. Swelling ability and drug release of beads in alkaline medium was substantial as that of acidic medium. Formulations showed non-Fickian transport mechanism. The results of the study indicate that drug-loaded pH sensitive IPN beads could be used to diminish drug release in an acidic medium and to regulate the drug release in alkaline medium, which would help to minimize the gastric side effects of the model NSAID ibuprofen.

PH-sensitive interpenetrating polymer network microspheres of poly(vinyl alcohol) and carboxymethyl cellulose for controlled release of the nonsteroidal anti-inflammatory drug ketorolac tromethamine

In this study, we aimed to produce pH-sensitive microspheres for the controlled release of the nonsteroidal anti-inflammatory drug, ketorolac tromethamine (KT). For this purpose, an interpenetrating polymer network (IPN) of microspheres of poly(vinyl alcohol) (PVA)/sodium carboxymethyl cellulose (NaCMC) were prepared, based on different formulations using glutaraldehyde (GA) (0.66 M) and hydrochloric acid (HCl) (3%, v/v). The preparation conditions of the microspheres were optimized by considering the percentage of entrapment efficiency and swelling capacity of the microspheres, and their release data. The effects of PVA and NaCMC ratio on the release of KT for over a period of 6 h, at three pH values (1.2, 6.8, and 7.4), have been discussed.

Novel pH-sensitive IPNs of polyacrylamide-g-gum ghatti and sodium alginate for gastro-protective drug delivery

This article reports the development of pH-sensitive interpenetrating polymer network (IPN) microbeads using polyacrylamide-grafted-gum ghatti (PAAm-g-GG) and sodium alginate (SA) for gastro-protective controlled delivery of ketoprofen. We have synthesized PAAm-grafted-GG copolymer under microwave irradiation using cerric ammonium nitrate as reaction initiator; further, the PAAm-g-GG was converted to pH-sensitive copolymer through alkaline hydrolysis. Sophisticated instrumentation techniques were used to characterize PAAm-g-GG. The IPN microbeads of PAAm-g-GG and SA, pre-loaded with ketoprofen were prepared by dual crosslinking using Ca2+ ions and glutaraldehyde (GA). The IPN microbeads demonstrated excellent pH-sensitive behavior as noted in the pulsatile swelling test and scanning electron microscopy. IPN microbeads also showed larger amount of drug release in buffer solution of pH 7.4 as compared to drug release in solution of pH 1.2. The in vivo pharmacokinetic, pharmacodynamic and stomach histopathology studies conducted on wistar rats confirmed the pH-sensitive controlled release of ketoprofen; IPN microbeads retarded the drug release in stomach resulting in reduced adverse effects of ketoprofen.

PH-sensitive IPN hydrogel based on poly (aspartic acid) and poly (vinyl alcohol) for controlled release

Various pH-sensitive sequential interpenetrating polymer network (IPN) hydrogels were prepared by introducing poly (vinyl alcohol) (PVA) hydrogel into Poly (aspartic acid) (PASP) hydrogel by freeze-thawing treatment to obtain a novel drug delivery system to the intestine. The structure and the morphologies of the prepared hydrogels were studied by Fourier Transform Infrared Spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal behavior and crystallinity of the hydrogels were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Their pH-sensitive properties moreover were studied and the results revealed that both PASP hydrogel and IPN hydrogels exhibited excellent pH-sensitivity. Furthermore, the controlled drug release properties of the hydrogels were also evaluated and results indicated that by increasing the PVA fraction in the IPN hydrogel, the release of Naproxen sodium was improved. These results show that the IPN hydrogels could be a suitable carrier for site-specific drug delivery in the intestine.

KGM and PMAA based pH-sensitive interpenetrating polymer network hydrogel for controlled drug release

Sequential interpenetrating polymer networks (IPN) hydrogels based on konjac glucomannan (KGM) and poly(methacrylic acid) (PMAA) were prepared by immersion of a solution of methacrylic acid (MAA) monomer with cross-linker N,N′-methylenebisacrylamide (MBAAm) and initiating into a pre-fabricated dried KGM gel. Polymerization and cross-linking of MAA inside the KGM network resulted in a novel biodegradable pH-sensitive IPN hydrogel. The studies on the swelling behavior of IPN hydrogels reveal their sensitive response to environment pH value. It was possible to modulate the degree of swelling of the IPN gels by changing the KGM/PMAA ratio and the cross-linking density of the PMAA component. The KGM component in the IPN can be degraded by β-glycosidase Mannaway25L. In vitro drug release behavior of IPN hydrogels were investigated under different environments using model drugs 5-fluorouracil. The results suggested that such an IPN hydrogel can be exploited as carrier candidate for colon-specific drug delivery.

Thermo- and pH-sensitive IPN hydrogels based on PNIPAAm and PVA-Ma networks with LCST tailored close to human body temperature

Interpenetrating polymer network (IPN) hydrogels based on chemically modified poly(vinyl alcohol) (or PVA-Ma), with different degrees of substitution (DS), and poly(N-isopropylacrylamide) (or PNIPAAm) were obtained and characterized in this work. The PVA-Ma/PNIPAAm membrane hydrogels were prepared in two steps. In the first step the PVA-Ma hydrogels (with using PVA-Ma with different DS) were prepared by the reaction of double bonds on PVA-Ma, using the persulfate/TEMED pathway. In the second step the PNIPAAm network was prepared within the parent PVA-Ma network at different PVA-Ma/NIPAAm ratios using a photoreaction pathway. The studies show that degree of swelling of PVA-Ma/PNIPAAm IPN hydrogels is dependent on both temperature and pH of the soaking solution. The LCST of PVA-Ma/PNIPAAm IPN hydrogels, which was determined by measuring the intensity of light transmitted through the swollen hydrogels, can be tailored closer to human body temperature. Furthermore, SEM images showed that the IPN hydrogels present characteristic morphology as compared to parent PVA-Ma networks. IPN hydrogels presented lower cytotoxicity as compared to respective PVA-Ma hydrogels but the increase in the PVA-Ma/NIPAAm ratio allows the respective hydrogels being lesser cytocompatibles. The IPN hydrogels synthesized in this work presented characteristics that potentize their application as biomaterials, drug carriers, artificial muscles and treatment of wound.

Moth wing scales as optical pH sensors

We embed individual wing scales from Chrysiridia rhipheus (sunset moth) into pH sensitive interpenetrating polymer network (IPN) of chitosan and PVA to generate novel pH sensors based on “biological physical dye”. The immobilized wing scales’ visible reflectance is responsive to pH conditions, owing to their inner microstructural changes induced by the IPN volume change in the swelling/deswelling process of hydrogel. In neutral and acidic environments, the in situ reflectance peaks of wing scales slightly shift ∼27nm around 730nm for pH 1.00–7.07, while in basic environments the peaks obviously blueshift ∼260nm from ∼730nm at pH 7.07 to ∼470nm at pH 13.74. Such prominent pH sensitivity of “moth scale indicators” in week basic conditions (pH 7.95–9.99) promises a bio-sensing pH monitor that can be used in bio-medical and bio-controlled applications.

Temperature- and pH-sensitive interpenetrating polymer networks grafted on PP: Cross-linking irradiation dose as a critical variable for the performance as vancomycin-eluting systems

This work focuses on the effect of gamma-ray radiation conditions on the stimuli-responsiveness and drug-eluting performance of polypropylene (PP) substrates grafted with interpenetrating networks of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc). PNIPAAm was cross-linked applying 10–100kGy doses in the presence and absence of the chemical cross-linker N,N′-methylenebisacrylamide (MBAAm). Then, the net-PP-g-PNIPAAm was interpenetrated with PAAc synthesized under a 2.5kGy dose to obtain net-PP-g-PNIPAAm-inter-net-PAAc films. The amount of grafted PNIPAAm (80%, 125% and 145% levels) and the cross-linking radiation dose (10, 40 and 70kGy levels) strongly determine the interpenetration of PAAc, the swelling degree, the amount of vancomycin loaded and its release rate. The chemical cross-linker only caused a minor decrease in the degree of swelling. The higher the PNIPAAm grafted on PP and the lower the cross-linking radiation dose, the more the PAAc in the IPN and, consequently, the higher the vancomycin loaded through specific interactions and the more sustained the release (>8h). The films possessing these features exhibited vancomycin release rate per surface unit suitable to prevent bacterial growth. Thus, adequate tuning of the radiation doses during grafting and cross-linking of the PNIPAAm networks may enable to achieve surface-modified materials for medical devices with an antibiofilm performance.

A novel pH sensitive porous membrane carrier for various biomedical applications based on pHEMA/chitosan: preparation and its drug release characteristics

AbstractThe synthetic hydrogels based on pHEMA have been widely studied and used in biomedical fields. Numerous techniques exist for entrapment of drugs or proteins in the hydrogels. The suitable biomaterials for biomedical applications include poly(hydroxyethyl methacrylate), (pHEMA), and chitosan. In this work, a novel pH sensitive interpenetrating polymer networks (IPNs) were prepared in the membrane form by using 2‐hydroxyethyl‐methacrylate monomer (HEMA) and chitosan via UV initiated photo‐polymerization in the presence of an initiator (i.e., α‐α;′‐azo‐isobutyronitrile; AIBN). UV‐free‐radical polymerization techniques are often used to synthesize hydrogels for controlled release applications. A series of HEMA and chitosan IPNs hydrogels were prepared and the equilibrium swelling studies were conducted to investigate swelling behaviors of the membrane according to the pH of the swelling medium. The swelling properties of the membrane were changed with the medium pH. The equilibrium water uptake is reached in about 60 min. The pHEMA/chitosan membrane thickness and density was measured to be 600 μm and 1.26 g cm−3, respectively. Antibiotic release experiments were also performed with amoxicillin loaded pHEMA/chitosan membrane in physiological saline solution. The IPNs membrane loaded with 100 mg antibiotic (i.e., amoxicillin) g hydrogel released around 80% of the amoxicillin in 10 h at pH 7.4. The presented well‐characterized novel pHEMA/chitosan membrane is a potential candidate for transdermal antibiotic carrier or a support in bioseparation.

Drug releasing characteristics of thermo- and pH-sensitive interpenetrating polymer networks based on poly (N-isopropylacrylamide)

Interpenetrating polymer networks (IPNs) of poly(N-isopropylacrylamide)/polyurethane (PNIPAAm/PU) and poly(N-isopropylacrylamide)/poly(acrylic acid) (PNIPAAm/PAA) were synthesized to investigate the swelling and drug releasing behavior. The presence of urethane network in PNIPAAm/PU IPNs improved the mechanical strength, but reduced the swelling and drug releasing rates because of its hydrophobic characteristics. The swelling transition temperatures of PNIPAAm gels were little affected by the incorporation of PU networks in IPN structures. The drug releasing process was analyzed with a simple exponential expression of time dependent fractional drug release. The swelling and drug releasing behavior of PNIPAAm/PAa IPNs was significantly affected by the variation of PAA compositions. The drug release process changed from anomalous to dual type via zero-order mode with increasing PAA concentration due to the competitive swelling rates between PNIPAAm and PAA during release process. The releasing rate decreased in the buffer solution of pH 7.4, but increased in that of pH 5.0 with increasing PAA concentration at both 28 and 37°C because the swelling power of PAA in pH 5.0 was much less than that in pH 7.4. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 2647–2655, 1997

Drug release from pH-sensitive interpenetrating polymer networks hydrogel based on poly (ethylene glycol) macromer and poly (acrylic acid) prepared by UV cured method

Acrylate-terminated poly (ethylene glycol) (PEG) macromer was prepared by the reaction of PEG with acryloyl chloride. Photopolymerization of PEG macromer resulted in the formation of cross-linked PEG network. Interpenetrating polymer networks (IPNs) based on PEG and poly(acrylic acid) (PAA) was obtained via template polymerization of AA to the PEG network by UV curing. The swelling degree of the IPNs hydrogel increased with an increase of pH value due to the association-dissociation between carboxylic acid of PAA and ether of PEG through hydrogen bonding. The swelling-deswelling behavior proceeded reversibly for the IPNs upon changing pH. Release of indomethacin from the IPNs demonstrated “on-off” regulation with pH fluctuation.