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Modeling of stimulated hydrogel volume changes in photonic crystal Pb2+ sensing materials.

We modeled the stimulated hydrogel volume transitions of a material which binds Pb2+ and is used as a photonic crystal chemical sensing material. This material consists of a polymerized crystalline colloidal array (PCCA) hydrogel which contains a crown ether molecular recognition group. The PCCA is a polyacrylamide hydrogel which embeds a crystalline colloidal array (CCA) of monodisperse polystyrene spheres of approximately 100 nm. The array spacing is set to diffract light in the visible spectral region. Changes in the hydrogel volume induced by Pb2+ binding alter the array spacing and shift the diffracted wavelength. This system allows us to sensitively follow the hydrogel swelling behavior which results from the immobilization of the Pb2+ by the crown ether chelating groups. Binding of the Pb2+ immobilizes its counterions. This results in a Donnan potential, which results in an osmotic pressure which swells the hydrogel. We continue here our development of a predictive model for hydrogel swelling based on Flory's theory of gel swelling. We are qualitatively able to model the PCCA swelling but cannot correctly model the large responsivity observed at the lowest Pb2+ concentrations which give rise to the experimentally observed low detection limits for Pb2+. These PCCA materials enable stimulated hydrogel volume transitions to be studied.

Cations, Divalent↗

A novel single-step fabrication technique to create heterogeneous poly(ethylene glycol) hydrogel microstructures containing multiple phenotypes of mammalian cells.

In this study, a novel method for the one-step fabrication of stacked hydrogel microstructures using a microfluidic mold is presented. The fabrication of these structures takes advantage of the laminar flow regime in microfluidic devices, limiting the mixing of polymer precursor solutions. To create multilayered hydrogel structures, microfluidic devices were rotated 90 degrees from the traditional xy axes and sealed with a cover slip. Two discreet fluidic regions form in the channels, resulting in the multilayered hydrogel upon UV polymerization. Multilayered patterned poly(ethylene glycol) hydrogel arrays (60 mum tall, 250 mum wide) containing fluorescent dyes, fluorescein isothiocyanate, and tetramethylrhodamine isothiocyanate were created for imaging purposes. Additionally, this method was used to generate hydrogel layers containing murine fibroblasts and macrophages. The cell adhesion promoter, RGD, was added to hydrogel precursor solution to enhance fibroblast cell spreading within the hydrogel matrix in one layer, but not the other. We were able to successfully generate patterns of hydrogels containing multiple phenotypes by using this technique.

Animals↗

Characterization of methacrylated inulin hydrogels designed for colon targeting: in vitro release of BSA.

PURPOSE: To characterize methacrylated inulin hydrogels with respect to their release properties. METHODS: Proteins (bovine serum albumin or lysozyme) were used as model drugs and were loaded during or after hydrogel formation. Parameters such as the drug loading method, the molecular weight of the proteins, the initial drug loading concentration, the hydrogel feed composition, degree of substitution, and size of the hydrogel were investigated by determining the release of the model proteins from the hydrogels in a phosphate buffer solution. The biodegradable properties were investigated by studying the release of bovine serum albumin in a solution of inulinase. RESULTS: In vitro protein release from methacrylated hydrogels was influenced by factors such as the drug loading procedure and the molecular weight and loading concentration of the proteins. The feed composition and degree of substitution of inulin seem to be crucial in controlling both the extent and the rate of release. Protein release was clearly enhanced in the presence of inulinase, indicating the biodegradable properties of methacrylated inulin hydrogels. CONCLUSIONS: Several hydrogels show interesting properties with respect to the development of a colon-specific drug delivery system.

Colon↗

Effects of nitric oxide releasing poly(vinyl alcohol) hydrogel dressings on dermal wound healing in diabetic mice.

Healing of chronic wounds such as diabetic foot ulcers is a significant clinical problem. Methods of accelerating healing in these difficult lower extremity sites include use of growth factor-loaded gels, hyperbaric oxygen, grafts, and artificial skin replacements. Nitric oxide (NO) has been proposed as a possible active agent for enhancing wound healing. This study examines the in vitro and in vivo responses to a novel hydrogel that produces therapeutic levels of NO. A hydrogel wound dressing was fabricated using ultraviolet light-initiated polymerization from poly(vinyl alcohol) with a NO donor covalently coupled to the polymer backbone. NO release from the NO-modified hydrogel was shown to occur over a time period of up to 48 hours, and there was no associated decrease in fibroblast growth or viability in vitro associated with NO hydrogels. Fibroblasts in culture with NO hydrogels had an increased production of extracellular matrix compared with cells cultured without the NO hydrogels. Preliminary animal studies in a diabetic mouse, impaired wound healing model were conducted comparing low (0.5 mM) and high (5 mM) doses of NO. Time to complete closure was similar in control wounds and NO-treated wounds; however, at 8 days control wounds were significantly smaller than NO-treated wounds. By days 10 to 13 this delay was no longer apparent. Granulation tissue thickness within the wounds at days 8 and 15 and scar tissue thickness after wound closure were increased in animals exposed to higher dose NO hydrogels. The results of this study suggest that exogenous NO released from a hydrogel wound dressing has potential to modulate wound healing.

Animals↗

Bone-like tissue formation by three-dimensional culture of MG63 osteosarcoma cells in gelatin hydrogels using calcium-enriched medium.

The aim of this study was to investigate the effect of Ca(2+) concentration in culture medium on the promotion of osteogenesis by MG63 osteoblast-like cells and to prepare bone-like tissues by supplying Ca(2+)-enriched medium to MG63 cells immobilized in three-dimensional gelatin hydrogels. Human osteosarcoma MG63 cells were cultured on tissue culture dish under various Ca(2+) concentrations to evaluate the effect of Ca(2+) concentration on calcium deposition. When Ca(2+) concentration was 8 mM, the maximum calcium deposition was obtained at day 28. Then MG63 cells were entrapped in gelatin hydrogels cross-linked by transglutaminase and cultured for 28 days, either in a standard culture medium or in medium containing 8 mM Ca(2+). Effects of Ca(2+)-enriched medium on osteoblastic phenotype of MG63 cells in gelatin hydrogels were analyzed in terms of cell number, calcium deposition content, and alkaline phosphatase (ALP) activity. The characteristics of calcified gelatin hydrogels were evaluated by x-ray diffraction (XRD), histological analysis, and scanning electron microscopy (SEM). After 28 days of culture, no significant difference in cell numbers was found between the different culture conditions. However, calcium content of gelatin hydrogels with cells cultured in Ca(2+)-enriched media was significantly higher than that of hydrogels with cells cultured in standard Ca(2+) concentration medium. After 14 days of culture, ALP activity of cells cultured in Ca(2+)-enriched media was down-regulated compared with that of cells cultured in standard Ca(2+) concentration media. XRD analysis indicated the formation of hydroxyapatite in gelatin hydrogels cultured in the Ca(2+)-enriched media at day 14, and the XRD pattern of the composite at day 21 was almost similar to that of mouse tibia. Moreover, histological analysis and SEM analysis revealed that cross-sections of hydrogels cultured in Ca(2+)-enriched media had an organic/mineral layer structure analogous to that of mouse tibia.

Alkaline Phosphatase↗

An investigation of the discrete and continuum models of water behavior in hydrogel contact lenses.

PURPOSE: To investigate the water behavior in hydrogels of differing equilibrium water content (EWC) and to use these results to investigate the opposing discrete model (thermodynamically different classes of water exist in hydrogels) and continuum model (water behaves as a consequence of nonequilibrium conditions) of nonfreezing water in swollen hydrogels. METHODS: Differential scanning calorimetry (DSC) was used to obtain melting thermograms for five lenses of each of 12 hydrogel lens types. The gravimetric content of the nonfreezing water was subsequently determined from an integrated endotherm for water. The effect of anneal time on the amount of nonfreezing water obtained in samples was investigated before undertaking these measurements. The glass transition temperature (Tg) of each of the lens types was obtained with DSC to investigate how the Tg was related to the amount of nonfreezing water found in the hydrogels. RESULTS: Melting enthalpy increased with increasing anneal time and leveled off at 6 hours. Low-EWC lenses showed endotherms with a single melting peak at 0 degrees C. Materials with a higher EWC showed more complicated melting endotherms, with a broad shoulder occurring at temperatures below 0 degrees C. There was a statistically significant positive correlation between EWC and freezing water (R=0.95, P<0.0001), but the amount of nonfreezing water was similar for all lens materials. There was a statistically significant positive correlation between the Tg of the hydrogels and the theoretically derived weight fraction of nonfreezing water in the hydrogels required to bring the Tg of the gels down to 0 degrees C (R=0.99, P<0.0001) but not with the experimentally derived values (R=0.29, P=0.07). CONCLUSIONS: Low-EWC hydrogels have the lowest free-to-bound water ratios. That the experimentally derived values of nonfreezing water are different from the theoretically derived values creates doubt with the continuum model theory. The best model probably employs a combination of the discrete and continuum theories.

Calorimetry↗

Evaluation of polyethylene glycol based hydrogel for tissue sealing after laparoscopic partial nephrectomy in a porcine model.

PURPOSE: Polyethylene glycol (PEG) based hydrogel is available as a tissue sealant and hemostatic aid. We determined the long-term safety and efficacy of its use as a tissue sealant for laparoscopic partial nephrectomy in a porcine model. MATERIALS AND METHODS: A total of 16 swine were cycled to 1 control group and 3 treatment groups, which underwent laparoscopic partial nephrectomy with hemostasis achieved only with application of a biodegradable PEG based hydrogel. The 3 treatment groups were sacrificed at 2, 6 and 12 weeks, respectively. Humoral immune response to the hydrogel used in the porcine abdomen was examined using enzyme-linked immunosorbent assay to detect antibodies in the serum at 0, 2, 6 and 12 weeks. Cell mediated immune response was examined using a lymphocyte proliferation assay to measure the response of leukocytes to various mitogens and antigens, including the polymerized hydrogel, at the same intervals. RESULTS: Hemostasis was satisfactory after hydrogel application. No adverse effects in the immediate and delayed periods were noted. At 2, 6 and 12 weeks there were no significant differences in hemoglobin or creatinine levels, or in the humoral immune response by enzyme-linked immunosorbent assay. There was no significant difference between test and control pig reactivity to hydrogel as an antigen in the lymphocyte proliferation assay at any time point. Histologically by 6 weeks the animals had almost absorbed the hydrogel with acute inflammation and foreign body reaction resolving by 6 to 12 weeks. No deleterious effect to renal tubules was seen. CONCLUSIONS: Biodegradable PEG based hydrogel is effective for long-term use as an agent for hemostasis. There was no detectable humoral immune response and no cell mediated immune response to sealant after 2 weeks. This represents promising sealant technology and it should be further investigated for human use.

Animals↗

Novel biodegradable cholesterol-modified polyrotaxane hydrogels for cartilage regeneration.

Cholesterol was introduced to a hydrolyzable polyrotaxane (PRx), not only to improve cell proliferation and glycosaminoglycan (GAG) production, but also to control the degradation rate of the hydrogels. The cholesterol was introduced to hydrolyzable PRx species by threading many alpha-cyclodextrins (alpha-CDs) on a poly(ethylene glycol) (PEG) chain having hydrolyzable ester linkages at the terminals; the PRx species were then cross-linked with other PEGs to prepare cholesterol-modified PRx hydrogels. The degree of cholesterol substitution was varied in the range of 1-25%. These hydrogels were examined to clarify the effect of cholesterol groups on mechanical properties, erosion time and chondrocyte proliferation. Highly porous biodegradable cholesterol-modified PRx hydrogels were fabricated using a combination of potassium hydrogen carbonate (as an effervescent salt) and citric acid. This fabrication process enabled the homogeneous expansion of pores within the polymer matrices, leading to well-interconnected macroporous hydrogels with a mean pore size of around 200-400 microm, ideal for high-density chondrocyte seeding. Time to complete degradation of the hydrogels was shortened by increasing the degree of substitution due to the aggregation of alpha-CDs through hydrophobic interaction of cholesterol groups. The presence of approx. 10% cholesterol improved the chondrocyte proliferation and GAG production. The modification of cholesterols to PRx is a good approach for creating new biodegradable hydrogels in terms of chondrocyte culture and controlling degradation time of the hydrogels.

Animals↗

Hydrogel probe for iontophoresis drug delivery to the eye.

The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface. Transconjunctival and transscleral iontophoresis of gentamicin sulfate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel disc probes. Gentamicin concentrations in different eye segments were assayed using a fluorescence polarization immunoassay. Preliminary corneal toxicity was examined in rabbits using a current intensity of 2.5 and 5.1 mA/cm2 for 60 and 120 s. The most appropriate hydrogel is composed of HEMA, 2% EGDMA and 75% water. lontophoresis onto agar gel was found indicative for the evaluation of iontophoretic activity of a hydrogel. Transscleral iontophoretic treatment resulted in high concentrations of drugs in the posterior segments of the eye. Application of iontophoresis onto the rabbit eye caused a reversible swelling of the cornea which lasted a few hours after application. Low current iontophoresis using drug-loaded hydrogel has a potential clinical value in obtaining high drug concentration at posterior segments of the eye.

Animals↗

Preparation and characterization of stimuli-resistible hydrogels nano-coated with polyelectrolyte multilayer films.

Alginate (ALG) hydrogels were nano-coated with polyelectrolyte multilayer (PEM) films composed of poly(diallyldimethyl ammonium chloride) (PDDA) and poly(sodium 4-styrenesulfonate) (PSS). Non- and nano-coated ALG hydrogels were immersed into salt solutions (pH 6, ionic strength: 0.01 M), and the swelling behavior of these ALG hydrogels was observed by optical microscopy. The increases in the diameter of the 10-step coated ALG hydrogels were one fourth or less than that of the non-coated hydrogels. These results indicate that the characteristics of nano-coated ALG hydrogels remain unchanged independent of how the external environment is changed (e.g., pH, ionic strength). Consequently, tolerant ionic hydrogels may be prepared by the nano-coating of hydrogel surfaces with PEM films and may be useful for technological and biomedical applications.

Absorption↗

Characterization and evaluation of silk protein hydrogels for drug delivery.

The objective of this study was to characterize and evaluate the physicochemical properties and drug release profiles of hydrogels composed of silk protein (SP) polymers. SPs with a low MW (SPL, ca. 18 kDa) and a high MW (SPH, ca. 76 kDa) were used for preparing hydrogels. Both the random coil form and beta-sheet conformation simultaneously existed in the hydrogels according to Fourier-transformed IR determination. Morphologically, the hydrogels showed a sponge-like cross-linked structure produced by physical entanglement as well as chemical hydrogen and covalent bindings. The in vitro buprenorphine delivery from SPH hydrogels showed a slow-release effect, and a zero-order rate was obtained for all preparations. Drug release could be controlled by varying the SPH concentrations or incorporation of SPL into the systems. SP hydrogels showed a stronger barrier property for hydrophilic solutes than for hydrophobic solutes. The incorporation of SPH into Pluronic F-127 (PF-127) hydrogels changed the gel structure from amorphous micelles to a regularly interconnected texture with pores. Furthermore, SPH as an adjuvant polymer in PF-127 and chitosan hydrogels lowered and controlled the amount of drug released from those systems.

Analgesics, Opioid↗

Hydrogels for pharmaceutical and biomedical applications.

Hydrogels are crosslinked hydrophilic polymer structures that can imbibe large amounts of water or biological fluids. Hydrogels are one of the upcoming classes of polymer-based systems that embrace numerous biomedical and pharmaceutical applications. This review discusses various parameters of hydrogels such as surface properties, water content and swelling behavior, effect of nature of polymer, ionic content, and thermodynamics, all of which can influence the biomedical usage of hydrogels. Meanwhile, intelligent or environment-sensitive hydrogels and bioadhesive hydrogels continue to be important materials for medical applications; therefore, a part of this review is devoted to some of their important classes. Hydrogels are extensively used for various biomedical applications--tissue engineering, molecular imprinting, wound dressings materials, immunoisolation, drug delivery, etc. Thus, this review aims to throw light on the numerous applications that hydrogels have in the biomedical arena.

Biomedical Engineering↗

Initial tree establishment on blocky quarry waste ameliorated with hydrogel or slate processing fines.

Pocket planting reclamation techniques developed in the 1970s for revegetating blocky quarrying waste have met with very limited success, often because the low water-holding capacity of the waste and limited root development within a small volume of planting pocket material result in severe drought mortality. We tested pocket planting approaches for waste tip reclamation at Europe's largest slate quarry, and compared materials for enhancing the continuity of water- and nutrient-holding down into the interior of the waste tip. When small compost-filled pocket planting bags were placed above slate processing fines (SPF) or water absorbent cross-linked polyacrylamide gel ("hydrogel"), tree growth rates increased in comparison with pocket planting bags alone. The SPF significantly improved tree survival especially during severe drought, but survival was not enhanced by the use of hydrogel. The sorption characteristics of hydrogel indicated that its presence may help to reduce nutrient leaching, but that it may have a negative effect on nitrogen availability. A more likely explanation for the poor performance of pure hydrogel is that it did not maintain sufficient available water, because of discontinuities caused by shrinkage and movement of the hydrogel, and/or degradation of water-holding capacity with environmental exposure. However, the root growth observed in the hydrogel treatments suggests that this technique, if adapted to reduce the effects of hydrogel shrinkage by using finer-grade hydrogel, mixing it with other soil-forming material, and reducing its exposure to extremes of temperature or sunlight, might have the potential to improve the growth and survival of trees planted on sites where delivery of heavy materials such as SPF is impractical. Fine mineral processing waste is freely available at active quarries and should be seen as a key resource for reclamation schemes.

Conservation of Natural Resources↗

Homotopic grafts of septal neurons combined to polymeric hydrogels placed into a fimbria-fornix lesion cavity attenuate locomotor hyperactivity but not mnemonic dysfunctions in rats.

PURPOSE: We studied the behavioral effects of an intracavitary implantation of poly[N-(2-hydroxypropyl)-methacrylamidel (PHPMA) hydrogels combined to intraseptal grafts of fetal septal cell suspensions in adult female rats subjected to aspirative fimbria-fornix lesions. The hydrogels were used as substrates for bridging the lesion cavity between the septum and the hippocampus. METHODS: Control groups included sham-operated or lesion-only rats, as well as lesioned rats with only the hydrogel bridge in the lesion cavity, only the graft in the septum, or an intrahippocampal graft of a septal cell suspension as a control for the standardly used ectopic transplantation strategy. Up to 10 months after grafting surgery, all rats were tested for locomotor activity in their home cage, sensorimotor performances using a beam-walking test, and cognitive performances in a radial maze, a water maze and a T-maze (rewarded alternation). RESULTS: The lesions induced hyperlocomotion, sensorimotor disturbances and severe alterations of cognitive functions. We found that neither the grafts or the hydrogels, nor the combination of both, induced any significant enhancement of sensorimotor or cognitive performances. Nevertheless, in rats with both intraseptal (homotopic) grafts and a hydrogel implant, the locomotor activity did no longer differ from that found in sham-operated controls. Histological analysis showed that the hydrogels contained acetylcholinesterase(AChE)-positive fibers and that the hippocampal region in contact with the hydrogel exhibited AChE-positive reaction products over several hundreds of micrometers. CONCLUSIONS: These results are complementary to our previous report on electrophysiological evidence of septo-hippocampal reconnections (Duconseille et al., Rest. Neurol. Neurosci. 15, 1999, 305-317). They further suggest that septal neurons grafted homotopically and/or neurons from the host brain are able to elongate axonal processes through a PHPMA substrate up to the hippocampus. Although they did not affect the cognitive consequences of the lesion, the changes enabled by the homotopic grafts combined to the hydrogel have attenuated the lesion-induced hyperactivity.

Animals↗

Tear exchange under hydrogel contact lenses: methodological considerations.

PURPOSE: To characterize hydrogel lens tear exchange and to apply an optimized method to compare tear exchange of a marketed hydrogel lens to that measured with a prototype silicone hydrogel lens. METHODS: Fluorophotometry and a nonpenetrating tracer (70-kDa FITC-dextran) were used with a single extended-wear soft contact lens (EWSCL) material on 11 subjects to characterize tear-exchange kinetics. Twenty to 30 measurements were obtained over a 30-minute period to allow accurate modeling and estimation of the several tear-exchange parameters. Calculated values included tear-replenishment rate (TRR), elimination rate (ER), and the time for 95% of the signal to be eliminated (T(95)). Major experiments were (1) comparison of ER under controlled and physiological conditions, (2) comparison of right and left eyes, (3) repeatability of ER and T(95) on five occasions, and (4) comparison of a marketed lens (oxygen permeability [Dk] 28 x 10(-9) [cm/sec][ml O(2)/ml mm Hg]) to a prototype silicone hydrogel lens (Dk 140 x 10(-9) [cm/sec][ml O(2)/ml mm Hg]). RESULTS: Tracer elimination behind a hydrogel contact lens (CL), up to 30 minutes after insertion, was optimally described by double-exponential kinetics. Physiological ER (5-30 minutes after CL insertion) was optimally described by single-exponential kinetics. Overall, physiological ER was 8.8% +/- 3.8% per minute, and T(95) was 31.0 +/- 16.1 minutes (n = 76 and 72 determinations, respectively). Differences between right and left eyes in ER and T(95) were not significant at the 0.05 level. No difference in ER or T(95) was found between habitual and controlled blinking. Mean TRR was 0.67% +/- 0.26% per blink (n = 11 determinations). No differences were shown between ER or T(95) measurements over time. A prototype highly oxygen-permeable silicone hydrogel lens showed higher ER than did a marketed hydrogel lens (P < 0.01). CONCLUSIONS: Estimates of postlens tear exchange using a slit lamp fluorophotometer are similar to previously reported rates using similar fluorophotometric techniques. Fluorescent decay behind a hydrogel lens is most precisely described using a double-exponential curve equation and tear exchange may be described using ER, TRR and T(95), although the T(95) may be the least reliable of these measures. The technique appears capable of discriminating between lens types.

Adult↗

Estimation of human corneal oxygen consumption by noninvasive measurement of tear oxygen tension while wearing hydrogel lenses.

PURPOSE: To devise a procedure for direct estimation of corneal oxygen consumption in human subjects. METHODS: Tear oxygen tension (PO2) was measured at the posterior surface of two standard hydrogel contact lenses (38% water, 0.2 and 0.06 mm thick, oxygen transmissibility [Dk/t] = 4.2 and 14 x 10(-9) cm x mL O2/mL x sec x torr) and one newly available hydrogel-silicone polymer lens (Dk/t = 99 x 10(-9)). The oxygen-sensitive dye, Pd-meso-tetra (4-carboxyphenyl) porphine, bound to bovine serum albumin, was incubated with the lenses overnight. The lenses, coated with the protein-dye complex, were placed on four subjects' eyes, and tear PO2 was measured in the open eye and after 5 minutes of eye closure, using a time-domain phosphorescence measurement system. Given the tear PO2, lens Dk/t, and corneal thickness, oxygen consumption (Q(C), in mL O2/cm(3) x sec) could be calculated from established oxygen diffusion models. RESULTS: Protein-dye complex bound to the lens surface enabled reporting of tear PO2 for long periods. As expected, estimated tear PO2 was higher in subjects wearing lenses with higher Dk/t: mean open-eye PO2 = 30.6 +/- 3.1 and 8.1 +/- 1.3 torr for the thin and thick hydrogel lenses, respectively, and 97.6 +/- 22.9 torr for the hydrogel-silicone lens. After 5 minutes of eye closure, tear PO2 was significantly reduced and reached a new steady state in approximately 20 seconds after eye opening. Fitting a single exponential model to the data and extrapolating to t = 0 provided an estimate of PO2 under the closed lid for the thin hydrogel (PO2 = 7 +/- 2.3 torr) and the hydrogel-silicone lens (PO2 = 22.6 +/- 4 torr). After 5 minutes of eye closure with the thick hydrogel lens, tear PO2 remained constant for approximately 10 seconds after eye opening (mean PO2 = 3.9 +/- 0.7) before increasing to a new steady state. This delay could be accounted for by the time needed for oxygen to diffuse to the posterior surface of the lens. Calculated Q(C) ranged from 2.2 x 10(-4) to 3.7 x 10(-6) mL O2/cm(3) x sec) at the highest and lowest PO2s, respectively, and is comparable to previous in vitro and in vivo estimates. CONCLUSIONS: Tear PO2 behind hydrogel lenses can be measured in human subjects using the phosphorescence of the porphyrin-protein complex bound to the lens surface. The method is simple, fast, reliable, and noninvasive, allowing quick and direct estimates of Q(C). In addition to contact lens wear, this method should be useful for examining the effects of disease, surgery, or topical drugs on the corneal oxygen consumption rate.

Adult↗

Effect of binder additives on terbutaline hydrogels of alpha-PVA/NaCl/H(2)O system in drug delivery: I. Effect of gelatin and soluble starch.

In order to prepare ecologically and biologically safety physical cross-linked hydrogel of a-PVA/NaCl/H(2)O system, we prepared blend hydrogel of natural polymeric binders like gelatin and starch in above system, and effect of these binder additives were evaluated on terbutaline release kinetics. Terbutaline (1%) hydrogels of a-PVA(7%)/NaCl(11%)/H(2)O and a-PVA(7%)/H(2)O system (Cyclic FT process) were prepared along with various concentrations of gelatin and soluble starch by feed-mixture dissolving method. In case of a-PVA/NaCl/H(2)O system only one cycle gelation was done at -20 degrees C for 24 h. On the other hand 3 cycles were done by freezing at -30 degrees C for 16 h followed by thawing at room temperature for 8 h. Drug release was done by paddle method (USP type II) with a rotation of 50 rpm at 37 degrees C in distilled water. Swelling of the gel was done at 37 degrees C for 45 h and melting temperatures of the gel were also studied using the upside-down test tube method. Comparatively lower values of release rate, diffusion coefficient and kinetic constant were found from the blend hydrogel of a-PVA/starch/NaCl/H(2)O system. When % cumulative release was plotted vs. square root of time it showed straight lines, which indicated Higuchi Matrix Dissolution Model. Inclusion of starch binder increased the degree of swelling compared with that of gelatin. 15 h was found as equilibrium swelling time. A Fickian swelling of this blend hydrogel system indicated the swelling controlled Fickian diffusion type of drug release. Melting temperatures of the blend hydrogels were characteristically higher (94-95 degrees C) than that of cyclic FT (72-76 degrees C), resulting a thermostable hydrogel for biological system. SEM morphological studies of gel surface indicated the well-developed interpenetrating macromolecular network structure like fish net in starch blend gel prevails over other hydrogel studied here. Gelatin has got characteristic tunnel (200 microm in diameter) inside the macromolecular network that contributes this system higher release kinetics than that of starch.

Absorption↗

Thermo-responsive hydrogels based on acryloyl-L-proline methyl ester and their use as long-acting testosterone delivery systems.

New thermo-responsive hydrogels were synthesized by copolymerizing acryloyl-L-proline methyl ester (A-ProOMe) with minor amounts of 2-hydroxypropyl methacrylate (HPMA) or polyethylene glycol 600 dimethacrylate (14G), using gamma-rays from a 60Co source. In water, extensive swelling of the hydrogels occurred at 10 degrees C, but there was marked deswelling as the temperature was raised to 37 degrees C. The poly(A-ProOMe-co-HPMA) hydrogel was characterized by an initial rapid shrinkage at the surface in the deswollen state; this shrinkage arose because of the formation of a rigid membrane barrier devoid of micropores. The system is therefore 'surface regulated'. In contrast, no such a barrier formed in the deswollen poly(A-ProOMe-co-14G) hydrogel. The whole matrix shrunk without the disappearance of micropores, and it is therefore a 'matrix pumping' system. Testosterone was incorporated into both these types of hydrogels, and the drug-loaded hydrogels were implanted subcutaneously into the backs of castrated rats. The daily dose of testosterone released in vivo from the poly(A-ProOMe-co-HPMA) hydrogel was constant at approximately 30 micrograms/day throughout an experimental period of 54 weeks. In contrast, drug release from the poly(A-ProOME-co-14G) hydrogel reached a maximum after one week and then decreased linearly with time down to the 7th week, when it was undetectable. These conclusions were supported by the changes in weight of the ventral prostates and right-side seminal vesicles of the rats, which were restored to normal when delivery of the testosterone was sustained.

Animals↗