Radiation crosslinked psyllium and polyacrylic acid based hydrogels for use in colon specific drug delivery

In order to utilize the psyllium husk, a medicinally important natural polysaccharide, to develop the hydrogels meant for the drug delivery, we have prepared psyllium and polyacrylic acid based polymeric networks by radiation-induced crosslinked copolymerization. Polymeric networks (hydrogels) thus formed were characterized with SEMs, FTIR and swelling studies. Swelling behavior of the hydrogels was studied as a function of monomer concentration in the hydrogels and temperature, pH and [NaCl] of the swelling medium. This paper discusses the swelling kinetics of the hydrogels and release dynamics of anticancer model drug 5-fluorouracil from the hydrogels for the evaluation of swelling and drug release mechanisms. It has been observed from the release dynamics of drug that diffusion exponent ‘n’ have 0.7, 0.8 and 0.7 values and gel characteristics constant ‘k’ have 9.13 × 10⁻³, 6.22 × 10⁻³ and 9.01 × 10⁻³ values for the release of 5-fluorouracil, respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer. The values of the diffusion exponent show that the release of drug from drug-loaded hydrogels has occurred through Non-Fickian diffusion mechanism. It has also been observed from the swelling and release of drug in the different pH buffer that the polymer matrix is pH responsive and can be exploited for the delivery of anticancer drug to the colon.     

Radiation crosslinked polymerization of methacrylamide and psyllium to develop antibiotic drug delivery device

Psyllium is a medicinally important polysaccharide and its modification with methacrylamide through radiation crosslinked polymerization will develop hydrogels meant for drug delivery applications. The present paper deals with the preparation of hydrogels and their characterization by SEMs, FTIR, TGA and swelling studies. The release dynamics of model antibiotic drug rifampicin from the hydrogels has been studied for the evaluation of the release mechanism. The values of the diffusion exponent ‘n’ have been obtained (0.64, 0.58 and 0.57), respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer. The release of the drug from the hydrogels occurred through non-Fickian diffusion mechanism.     

Synthesis, characterization and swelling studies of pH responsive psyllium and methacrylamide based hydrogels for the use in colon specific drug delivery

In order to utilize the psyllium husk a medicinally important natural polysaccharide and to develop the novel hydrogels meant for the colon specific drug delivery, we have prepared psyllium and methacrylamide based polymeric networks by using N,N′-methylenebisacrylamide (NN-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator. To study various structural aspects of the polymeric networks thus formed psy-cl-poly(MAAm), these were characterized with SEMs, FTIR, TGA and swelling studies. The swelling studies of networks were carried out as a function of time, temperature, pH and [NaCl]. Equilibrium swelling has been observed to depend on both composition of the polymer and nature of swelling medium. Maximum percent swelling 1262 was observed for the polymeric network prepared with 19.45 × 10⁻³ mol/L of [NN-MBAAm] at 40 °C in 0.5 M NaOH solution. This article also discusses the release dynamics of tetracycline hydrochloride from the hydrogels, for the evaluation of the drug release mechanism and diffusion coefficients of drug from the polymer matrix. The effect of pH on the release pattern of tetracycline hydrochloride has been studied by varying the pH of the release medium. It has been observed from the release dynamics of drug from the hydrogels that the diffusion exponent ‘n’ have 0.477, 0.423 and 0.427 values and gel characteristic constant ‘k’ have 5.07 × 10⁻², 6.34 × 10⁻² and 6.38 × 10⁻² values, respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer solution. The values the ‘n’ indicated that the Fickian type diffusion mechanism occurred for the release of tetracycline hydrochloride from drug loaded psy-cl-poly(MAAm) polymers in different release mediums. In Fickian type diffusion mechanism, the rate of polymer chain relaxation is more as compare to the rate of drug diffusion from these hydrogels and release behavior follows Fick’s law of diffusion. In each release medium, the values of the initial diffusion coefficient ‘D_i’ for the release of tetracycline hydrochloride was higher than the values of late time diffusion coefficient ‘D_L’ indicating that in the start, the diffusion of drug from the polymeric matrix was faster as compare to the latter stages.     

The release dynamics of salicylic acid and tetracycline hydrochloride from the psyllium and polyacrylamide based hydrogels (II)

Psyllium, a medicinally active natural polysaccharide, has been modified with polyacrylamide to develop the hydrogels; those can act as the potential candidate for novel drug delivery systems. In the present studies, the release dynamics of model drugs (salicylic acid and tetracycline hydrochloride) from the drug-loaded hydrogels have been discussed, for the evaluation of the drug release mechanism and diffusion coefficients. It has been observed that diffusion exponent ‘n’ have 0.68 and 0.74 values and gel characteristic constant ‘k’ have 1.625 × 10⁻² and 1.272 × 10⁻² values, respectively, for the release of salicylic acid and tetracycline hydrochloride in distilled water from the drug loaded hydrogels. Therefore, drug release from the drug loaded hydrogels through Non-Fickian or Anomalous diffusion mechanism where the rate of drug diffusion and rate of polymer relaxation were comparable. The effect of pH on the release pattern of tetracycline has been studied by varying the pH of the release medium. However, in each release medium, the Initial diffusion coefficient was observed to be more than the late time diffusion coefficient.     

pH-sensitive cationic guar gum/poly (acrylic acid) polyelectrolyte hydrogels: Swelling and in vitro drug release

Novel polyelectrolyte hydrogels (coded as GA) based on cationic guar gum (CGG) and acrylic acid monomer by photoinitiated free-radical polymerization were synthesized with various feed compositions. Fourier transform infrared spectra (FTIR), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) confirmed that the formation of the polyelectrolyte hydrogels was attributed to the strong electrostatic interaction between cationic groups in CGG and anionic groups in poly (acrylic acid) (PAA). Swelling experiments provided important information on drug diffusion properties, which indicated the GA hydrogels were highly sensitive to pH environments. Potential applications of the hydrogels matrices in controlled drug delivery were also examined. The ketoprofen-loaded CGG/PAA matrices were prepared by hydrogels and directly compressed tablets, respectively. Release behavior of ketoprofen relied on the preparative methods of matrices, ratios of CGG/AA and pH environments. The release mechanism was studied by fitting experimental data to a model equation and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in pH 7.4 buffer solution was mainly non-Fickian diffusion. However, for tablets, the drug release in pH 7.4 buffer solution was mainly affected by polymer erosion. The pH of the dissolution medium appeared to have a strong effect on the drug transport mechanism. At more basic pH values, Case II transport was observed, indicating a drug release mechanism highly influenced by macromolecular chain relaxation. The ketoprofen release is also tested in the conditions chosen to simulate gastrointestinal tract conditions. The results implied that the GA hydrogels can be exploited as potential carriers for colon-specific drug delivery.     

Poly(ethylene glycol) methacrylate/dimethacrylate hydrogels for controlled release of hydrophobic drugs

Hydrogels have been successfully used to entrap hydrophilic drugs and release them in a controlled fashion; however, the entrapment and release of hydrophobic drugs has not been well studied. We report on the release characteristics of a model hydrophobic drug, the steroid hormone estradiol, entrapped in low (MW 360/MW 550) and high (MW 526/MW 1000) molecular weight poly(ethylene glycol) methacrylate (PEG-MA)/dimethacrylate (PEG-DMA) hydrogels. The cross-linking ratio, temperature, and pH ranged from 10:1 to 10:3, from 33 to 41 degrees C, and from 2 to 12, respectively. The gelation of the PEG-MA/PEG-DMA hydrogel was initiated with UV irradiation. The absence of poly(glutamic acid) in the hydrogel formulation resulted in a loss of pH sensitivity in the acidic range, which was displayed by the hydrogels' similarities in swelling ratios in the pH buffers of pH 2, 4, and 7. Use of high molecular weight polymers resulted in a higher hydrogel swelling (300%) in comparison to the low molecular weight polymers. Drug size was found to be a significant factor. In comparison to 100% estradiol (MW 272) release, the fractional release of insulin (MW 5733) was 12 and 24% in low and high molecular weight gels at pH 2, respectively, and 17% in low molecular weight gels at pH 7. On the release kinetics of the estradiol drug, the hydrogels displayed a non-Fickian diffusion mechanism, which indicated that the media penetration rate is in the same range as the drug diffusion. The synthesis, entrapment, and release of estradiol by the PEG-MA/PEG-DMA hydrogels proved to be successful, but the use of ethanol in the buffers to promote the hydrophobic release of the estradiol in the in vitro environment caused complications, attributed to the process of transesterification.     

Release characteristics of novel pH-sensitive p(HEMA-DMAEMA) hydrogels containing 3-(trimethoxy-silyl) propyl methacrylate

An amphiphilic hydrogel of poly(2-hydroxyethyl methacrylate) cross-linked with tetraethyleneglycol diacrylate (TEGDA) was synthesized to contain the hydrophobic monomer 3-(trimethoxy-silyl) propyl methacrylate (PMA) and the pH-responsive, hydrophilic monomer N',N'-dimethylaminoethyl methacrylate (DMAEMA). The gels were separately loaded with two biomolecular probes, insulin and protamine, via both physical entrapment and equilibrium imbibition methods. The release profiles for these biomolecular probes, possessing similar MW (5.7 and 4-6 kDa, respectively) but different pI's (5.3 and 10.0, respectively), were investigated with respect to variation in the pH of the bathing medium as well as the DMAEMA content, and the cross-link density of the hydrogel. Gels exhibited classical Fickian diffusion release profiles. For a typical gel composition 66:15:10:09 mol % (HEMA:DMAEMA:PMA:TEGDA), as the pH of the release media decreased from 7.3 to 4.0, the rate of release of both biomolecular probes increased. When loaded via entrapment, the insulin release rate increased ca. 4-fold (1.0-3.7 x 10(-7) cm(2) s(-1)), whereas that of protamine increased 10-fold (0.3-3.3 x 10(-7) cm(2) s(-1)). When loaded by imbibition, the insulin diffusion coefficient increased 2-fold (3.8-7.2 x 10(-7) cm(2) s(-1)), whereas that of protamine increased 3-fold (1.9-5.5 x 10(-7) cm(2) s(-1)). The reduction of pH, through its protonation of the gel network, has a more dramatic influence on protamine release, the result of its higher pI (10.0) compared to that of insulin (5.3). As the DMAEMA content of the hydrogel was increased from 0 to 20 mol %, the diffusion coefficient of protamine increased by ca. 7-fold (1.7-12.2 x 10(-7) cm(2) s(-1)), whereas that of insulin increased only ca. 2-fold (1.7-4.0 x 10(-7) cm(2) s(-1)). This differential release confirms the role of internal protonation in effecting the greater release of the protonated drug molecule. Increasing the TEGDA content from 3 to 15 mol % reduced the diffusion coefficient ca. 3-fold for insulin (1.6-0.5 x 10(-7) cm(2) s(-1)) and 5-fold for protamine (4.0-0.8 x 10(-7) cm(2) s(-1)). The final D(ip) at 15 mol % TEGDA suggests that the smaller mesh size offsets any differential release that arises from protonation. The presence of PMA in the hydrogel formulation, which contributes additional cross-links by reason of the formation of siloxane macromers, did not change the usually observed Fickian diffusion mechanism.     

Cytoplasmic hydrogen ion diffusion coefficient.

The apparent cytoplasmic proton diffusion coefficient was measured using pH electrodes and samples of cytoplasm extracted from the giant neuron of a marine invertebrate. By suddenly changing the pH at one surface of the sample and recording the relaxation of pH within the sample, an apparent diffusion coefficient of 1.4 +/- 0.5 x 10(-6) cm2/s (N = 7) was measured in the acidic or neutral range of pH (6.0-7.2). This value is approximately 5x lower than the diffusion coefficient of the mobile pH buffers (approximately 8 x 10(-6) cm2/s) and approximately 68x lower than the diffusion coefficient of the hydronium ion (93 x 10(-6) cm2/s). A mobile pH buffer (approximately 15% of the buffering power) and an immobile buffer (approximately 85% of the buffering power) could quantitatively account for the results at acidic or neutral pH. At alkaline pH (8.2-8.6), the apparent proton diffusion coefficient increased to 4.1 +/- 0.8 x 10(-6) cm2/s (N = 7). This larger diffusion coefficient at alkaline pH could be explained quantitatively by the enhanced buffering power of the mobile amino acids. Under the conditions of these experiments, it is unlikely that hydroxide movement influences the apparent hydrogen ion diffusion coefficient.     

Characterization and in vitro evaluation of starch based hydrogels as carriers for colon specific drug delivery systems

A series of starch/methacrylic acid (MAAc) copolymer hydrogels of different compositions were synthesized using γ-rays induced polymerization and crosslinking. The effects of the preparation conditions such as the feed solution concentration, feed solution composition and irradiation dose on the gelation process of the synthesized copolymer were investigated. The swelling behavior of the starch/methacrylic acid (MAAc) copolymer hydrogels was characterized by studying the effect of the hydrogel composition on the time- and pH-dependent swelling. Swelling kinetics showed that the synthesized hydrogels possessed Fickian diffusion behavior at pH 1 and non-Fickian diffusion at pH 7 which recommend them as good candidate for colon specific drug delivery systems. The synthesized hydrogels were loaded with ketoprofen as a model drug to investigate the release behavior of the synthesized hydrogels. The results showed the ability of the hydrogels to keep the loaded drug at pH 1 and release it at pH 7. The data also showed that the release rate can be controlled by controlling the preparation conditions such as comonomer concentration and composition and irradiation dose.     

Radiation crosslinking polymerization of sterculia polysaccharide-PVA-PVP for making hydrogel wound dressings

The present study deals with the modification of sterculia gum by PVA-PVP through radiation crosslinking, to develop the hydrogels meant for the delivery of antimicrobial agent to the wounds. The hydrogels were characterized by SEM, FTIR, TGA and swelling studies. For the evaluation of swelling and drug release mechanism, the swelling kinetics and in vitro release dynamics of model drug from this matrix have been studied respectively in the solution of different pHs and simulated wound fluid. After 24h swelling per gram of the hydrogel has taken (17.03±0.19)g of simulated wound fluid and has released (0.230±0.01)mg of drug in the simulated fluid. The release of drug in simulated fluids occurred through non-Fickian diffusion mechanism.     

Matrix metalloprotease selective peptide substrates cleavage within hydrogel matrices for cancer chemotherapy activation

To utilize biologic mechanisms to elicit controlled release in response to disease, protease-sensitive devices have been created. Hydrogels were created with pendant peptide-drug complexes. For the matrix metalloproteases (MMPs) examined, a length of six amino acids greatly improved the specificity of the peptide (k(cat)/K(m) approximately 2.4+/-0.1x10(4)M(-1)s(-1)) over shorter sequences (k(cat)/K(m) approximately 4.4+/-0.2x10(2)M(-1)s(-1)). The peptides did not exhibit anti-proliferative effects upon cancer cells, and peptide-platinum complexes showed similar anti-proliferative effects upon the cancer cells compared to the free platinum drugs. Once the peptide-drug complex was incorporated into the hydrogels, the release was dependent upon the presence of MMP in the solution with approximately 35% of platinum released from hydrogels in the presence of MMP and only 10% without MMP in the week examined. The released drug exhibited the expected anti-proliferative activity over several days of incubation. The MMP selective drug delivery holds much potential for treatment of cancer and other diseases.     

Drug loading into and drug release from pH- and temperature-responsive cylindrical hydrogels

Hydrogels that undergo deformation upon appropriate changes in pH or temperature have considerable promise as drug delivery vehicles. Drug uptake in swelling and nonswelling cylindrical hydrogels and drug release from these into a target fluid are investigated here. A mathematical model for hydrogel-solution composite, a composite of a distributed parameter system (cylindrical hydrogel) and a lumped parameter system (surrounding solution), is developed. The polymer network displacement in a swelling/deswelling hydrogel is described by a stress diffusion coupling model. The analytical solution for network displacement is used to predict solvent intake by swelling hydrogels, solvent efflux from deswelling hydrogels, and changes in pressure, porosity, and effective drug diffusivity. These in turn influence drug uptake during and after hydrogel swelling and drug release from hydrogel during and after deswelling. Numerical results illustrate benefits of hydrogel swelling for drug loading and merits of different modes of drug release. Drug uptake and drug release by temperature-responsive hydrogels are compared with those by hydrogels not subject to deformation.     

Synthesis and characterization of pH-sensitive hydrogel composed of carboxymethyl chitosan for colon targeted delivery of ornidazole

In the present study, carboxymethyl chitosan was prepared from chitosan, crosslinked with glutaraldehyde and evaluated in vitro as a potential carrier for colon targeted drug delivery of ornidazole. Ornidazole was incorporated at the time of crosslinking of carboxymethyl chitosan. The chitosan was evaluated for its degree of deacetylation (DD) and average molecular weight; which were found to be 84.6% and 3.5×10(4) Da, respectively. The degree of substitution on prepared carboxymethyl chitosan was found to be 0.68. All hydrogel formulations showed more than 85% and 74% yield and drug loading, respectively. The swelling behaviour of prepared hydrogels checked in different pH values, 1.2, 6.8 and 7.4, indicated pH responsive swelling characteristic with very less swelling at pH 1.2 and quick swelling at pH 6.8 followed by linear swelling at pH 7.4 with slight increase. In vitro release profile was carried out at the same conditions as in swelling and drug release was found to be dependant on swelling of hydrogels and showed biphasic release pattern with non-fickian diffusion kinetics at higher pH. The carboxymethylation of chitosan, entrapment of drug and its interaction in prepared hydrogels were checked by FTIR, (1)H NMR, DSC and p-XRD studies, which confirmed formation of carboxymethyl chitosan from chitosan and absence of any significant chemical change in ornidazole after being entrapped in crosslinked hydrogel formulations. The surface morphology of formulation S6 checked before and after dissolution, revealed open channel like pores formation after dissolution.     

IPNs based on chitosan with NVP and NVP/HEMA synthesised through photoinitiator-free photopolymerisation technique for biomedical applications

Biocompatible interpenetration polymeric network (IPN) hydrogels based on chitosan with N-vinylpyrrolidinone (NVP) as well as its copolymer with 2-hydroxymethyl methacrylate (HEMA) were synthesised using the photopolymerisation technique without the inclusion of any photoinitiator or crosslinking agent. These hydrogels were characterised using the Fourier-transform infrared spectroscopy (FTIR) technique. Equilibrium swelling of these hydrogels was performed in Milli-Q water and drug release studies were carried out using theophylline as the model drug. These tests showed that the IPN comprised of chitosan and NVP with a very small amount of N-hydroxymethyl maleimide (HMMI) included exhibited higher swelling abilities and fast drug release rates than the IPN which contained chitosan, NVP and HEMA. Kinetic studies of water diffusion into these hydrogels and drug release revealed that with the exception of the IPN with HEMA incorporated, the other hydrogels did not adhere to the Fickian diffusion model. These hydrogels were tested for their biocompatibility with human epidermal keratinocyte cells (HaCaT). A positive cell growth as evidenced by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay indicated that these hydrogels are non-toxic to human keratinocytes and can be potentially used as biomaterials for biomedical applications.     

Photopolymerization of methacrylated chitosan/PNIPAAm hybrid dual-sensitive hydrogels as carrier for drug delivery

A series of hybrid hydrogels based on glycidyl methacrylated chitosan (CS-GMA) and N-isopropylacrylamide (NIPAAm) were designed and prepared via photopolymerization technology. The hydrogels were characterized by Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC) and optical transmittance. The interior morphology of hydrogels was investigated by scanning electron microscopy (SEM). The swelling experiment results revealed that hybrid hydrogel exhibited combined pH and temperature sensitivities. Acid orange 8 (AO8) and 5-flurouracil (5-Fu) were selected as model drugs for examining their release from hydrogels. The results suggested that hydrogel composition and pH value of buffer solution had great influences on release profiles.     

Electric Field-Controlled Benzoic Acid and Sulphanilamide Delivery from Poly(Vinyl Alcohol) Hydrogel

The controlled release of benzoic acid (3.31 Å) and sulphanilamide (3.47 Å) from poly(vinyl alcohol), PVA, hydrogels fabricated by solution casting at various cross-linking ratios, were investigated. The PVA hydrogels were characterized in terms of the degree of swelling, the molecular weight between cross-links, and the mesh size. The drug release experiment was carried out using a modified Franz diffusion cell, at a pH value of 5.5 and at temperature of 37°C. The amount of drug release and the diffusion coefficients of the drugs from the PVA hydrogels increased with decreasing cross-linking ratio, as a larger mesh size was obtained with lower cross-linking ratios. With the application of an electric field, the amount of drug release and the diffusion coefficient increased monotonically with increasing electric field strength, since the resultant electrostatic force drove the ionic drugs from the PVA matrix. The drug size, matrix pore size, electrode polarity, and applied electric field were shown to be influential controlling factors for the drug release rate.KEY WORDS: electrophoresis force, ionic drug delivery, iontophoresis, poly(vinyl alcohol)     

Natural polymer-based magnetic hydrogels: Potential vectors for remote-controlled drug release

The preparation and characterization of natural polymer-based hydrogels that contain 50-nm diameter magnetite (i.e., FeO:Fe(2)O(3)) nanoparticles are described herein. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the efficiency of the polysaccharide-modifying process. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and compressive moduli demostrate that the presence of magnetite improves thermal and mechanical resistance. Transient diffusion of water in magnetic hydrogels was analyzed via boundary layer mass transfer across an expaning interface, and the degree of swelling of these polysaccharide hydrogels decreases in the presence of magnetite, with no variation in the binary diffusion mechanism. The absence of hysteresis loops and coercivity observed via magnetometry suggests that magnetic hydrogels are useful for remote-controlled drug release, as demonstrated by magnetic-field-induced release of curcumin. Experiments reveal that magnetic hydrogels with greater magnetic susceptibility have the potential to release larger concentrations of drugs from the hydrogel network.     

Preparation and characterization of N-(2-carboxybenzyl)chitosan as a potential pH-sensitive hydrogel for drug delivery

A novel water-soluble chitosan derivative [N-(2-carboxybenzyl)chitosan, CBCS] was synthesized. The chemical structure of CBCS was characterized by FTIR, (1)H NMR and UV spectroscopies. The degree of substitution (DS) of N-2-carboxybenzyl was determined by colloid titration. In different pH buffer solutions, the swelling characteristics of hydrogels based on CBCS (CBCSG) prepared by crosslinking with glutaraldehyde have been studied. Results showed that the swelling ratio (SR) of CBCSG decreased with an increase of the amount of glutaraldehyde, and that CBCSG swelled more significantly in alkaline solution than in acidic medium, showing the lowest SR at pH5.0. The SR of CBCSG increased with the raising of the DS of the N-2-carboxybenzyl group in alkaline solution, but no significant change was observed in an acidic environment. CBCSG showed swelling reversibility when alternately soaked in pH1.0 and 7.4 buffer solutions. Release profiles of fluorouracil (5-FU), a poorly water-soluble drug, from CBCSG were studied under both simulated gastric and intestinal pHconditions. The release was much quicker in pH7.4 buffer than in pH1.0 solution. Results indicated that CBCS could be a potential pH-sensitive carrier for colon-specific drug delivery system.     

Preparation and properties of a pH/temperature-responsive carboxymethyl chitosan/poly(N-isopropylacrylamide)semi-IPN hydrogel for oral delivery of drugs

Thermo- and pH-responsive semi-IPN polyampholyte hydrogels were prepared by using carboxymethylchitosan and poly(N-isopropylacrylamide) with N,N'-methylenebisacrylamide (BIS) as the crosslinking agent. The swelling characteristics of these hydrogels at distinct compositions as a function of pH and temperature were investigated. It was found that the semi-IPN hydrogels demonstrated the pH- and temperature-responsive nature of the materials, and it also showed good reversibility. The study on the release of coenzyme A (CoA) showed that within 24h the cumulative release ratio of CoA was 22.6% in pH 2.1 solution and 89.1% in pH 7.4 solution at 37 degrees C, respectively. The release rate of CoA was higher at 37 degrees C than 25 degrees C in a pH 7.4 buffer solution. An increased release rate of CoA was observed with the content of carboxymethylchitosan increasing in the hydrogel at 25 degrees C in pH 7.4 solution. These results show that semi-IPN hydrogel seems to be of great promise in pH-temperature oral drug delivery systems.     

Thermo-sensitive chitosan based semi-IPN hydrogels for high loading and sustained release of anionic drugs

Thermo-sensitive poly(N-isopropyl acrylamide-co-vinyl pyrrolidone)/chitosan [P(NIPAM-co-NVP)/CS] semi-IPN hydrogels with improved loading capacity and sustained release for anionic drugs NAP were prepared by free-radical polymerization. The LCST of hydrogels was adjusted to the vicinity of body temperature by introducing hydrophilic NVP. The presence of CS in semi-IPN networks improves the swelling behavior and provides a high affinity for anionic drug NAP due to the strong interactions between NAP molecules and CS chains. Release of NAP was suppressed at pH 2.2 and 5.0 and accelerated at pH 7.4 due to the deprotonation of amino groups in CS. Increasing temperature above LCST, hydrogels showed a continuous release of NAP without burst diffusion due to the shrinkage of PNIPAM restraining the drug release.