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At least 19 recordsLinked to original sources
PubMed2001

Design of a rate- and time-programming drug release device using a hydrogel: pulsatile drug release from kappa-carrageenan hydrogel device by surface erosion of the hydrogel.

We have found that a repetitive pulsatile drug release with a certain time interval is observed from a monolithic hydrogel device by surface erosion of the hydrogel. As a model system of pulsatile drug release, dibucaine hydrochloride and kappa-carrageenan hydrogel were chosen as a drug and a device, respectively. Electrostatic interactions between dibucaine hydrochloride and kappa-carrageenan polymer segments are strong, since dibucaine hydrochloride is positively charged and each disaccharide repeating unit of kappa-carrageenan chains has one sulfate group. Dibucaine hydrochloride was loaded into the hydrogel by immersing dry kappa-carrageenan hydrogel disks in a dibucaine hydrochloride solution for 24 h. The pulsed release of dibucaine hydrochloride from the device was observed every 50 min between 30 and 250 min after the release starts. The weight of kappa-carrageenan hydrogel decreases in an oscillatory manner with time in distilled water. The oscillatory changes observed in the hydrogel weight in distilled water are considered to be caused by influx and efflux of water molecules into and from the surface and core of the hydrogel and by polymer liberation from the hydrogel. This phenomenon was well explained by our kinetic model [Colloids and Surfaces B 8 (1996) 93-100]. The time interval between pulses observed in drug release coincides with that observed in the oscillatory weight change of the hydrogel. From these, it was concluded that the pulsatile release of dibucaine hydrochloride from the device was caused by the pulsatile liberation of swollen kappa-carrageenan hydrogel from the surface of the device.

Journal Article↗
PubMed1999

Inulin hydrogels as carriers for colonic drug targeting. Rheological characterization of the hydrogel formation and the hydrogel network.

Free radical polymerization converts aqueous solutions of methacrylated inulin into cross-linked hydrogels. The purpose of this work was to study the hydrogel formation and to characterize the fully cured hydrogels. The gelation process of aqueous solutions of methacrylated inulin was monitored as a function of time by means of linear oscillatory shear measurements, at a fixed frequency and amplitude. The fully cured inulin hydrogels were characterized by measurement of the frequency-dependency of the linear elastic modulus G'. The effects of the degree of substitution and feed concentration of methacrylated inulin on both the gelation kinetics and the rigidity of the obtained hydrogels were determined. The effect of the concentration of the initiators of the radical polymerization reaction has been studied as well. The weight fraction of polymer which was not incorporated in the hydrogel networks was determined using the anthrone reaction, and physical chain entanglements were determined by solution viscosity measurements. The gelation kinetics and the elastic modulus were proportional to the degree of substitution and feed concentration of methacrylated inulin. Increasing concentrations of radical-forming compounds also accelerated the hydrogel formation, but lowered the elastic modulus of the obtained hydrogels. The amount of polymer chains incorporated in the hydrogel network seemed to be especially influenced by the degree of substitution of the derivatized inulin, and for a feed concentration of 27% w/w of methacrylated inulin, entanglements have to be accounted for. The gelation kinetics and the elastic modulus of inulin hydrogels are not only affected by the degree of substitution and the feed concentration of methacrylated inulin, but also by the concentration of the initiators of the free radical polymerization reaction.

Algorithms↗
PubMed2002

Controlled release of plasmid DNA from cationized gelatin hydrogels based on hydrogel degradation.

This paper shows achievement of the in vivo controlled release of a plasmid DNA from a biodegradable hydrogel and the consequent regulation of gene expression period. Cationization of gelatin was preformed through introduction of ethylenediamine and the gelatin prepared was crosslinked by various concentrations of glutaraldehyde to obtain cationized gelatin (CG) hydrogels as the carrier of plasmid DNA. In vivo release of plasmid DNA from the CG hydrogels was compared with the in vivo degradation of hydrogels. When CG hydrogels incorporating 125I-labeled plasmid DNA were implanted into the femoral muscle of mice, the plasmid DNA radioactivity remaining decreased with time and the retention period prolonged with a decrease in the water content of hydrogels used. The higher the water content of 125I-labeled CG hydrogels, the faster the hydrogel radioactivity remaining decreased with time. The time profile of plasmid DNA remaining in the hydrogels was in good accordance with that of hydrogel radioactivity, irrespective of the water content. Intramuscular implantation of plasmid DNA-incorporated CG hydrogels enhanced significantly expression of the plasmid DNA around the implanted site. The retention period of gene expression became longer as the hydrogel water content decreased. Fluorescent microscopic study revealed that the plasmid DNA-CG complex was detected around the hydrogel implanted even after 7-day implantation in marked contrast to the injection of plasmid DNA solution. It was concluded that in our hydrogel system, active plasmid DNA was released accompanied with the in vivo degradation of hydrogel, resulting in extended gene expression. The time profile of plasmid DNA release and the consequent gene expression was controllable by changing the water content of hydrogels.

Animals↗
PubMed2001

Controlled release of hepatocyte growth factor from gelatin hydrogels based on hydrogel degradation.

This paper investigates the controlled release of hepatocyte growth factor (HGF) by biodegradable gelatin hydrogels and their HGF-induced angiogenic effect. Hydrogels of different degradabilities were prepared through chemical crosslinking gelatin with varied amounts of glutaraldehyde. When the gelatin hydrogels were radioiodinated and subcutaneously implanted into the back of mice, the remaining radioactivity of the hydrogels decreased with time. However, the remaining period became longer when the concentration of glutaraldehyde used for hydrogel preparation increased. Following implantation of gelatin hydrogels incorporating 125I-labeled HGF, the HGF radioactivity retained in the mouse subcutis for longer time periods as the glutaraldehyde concentration becomes higher. The time profile of HGF remaining in every gelatin hydrogel was in good accordance with that of hydrogel degradation, indicating HGF release as a result of hydrogel biodegradation. The gelatin hydrogel incorporating HGF histologically induced angiogenic change around the implanted hydrogel. Gelatin hydrogels incorporating 5 and 10 microg HGF significantly enhanced the number of capillaries newly formed around the implanted site. This was in marked contrast to free HGF of same dose form and HGF-free, empty gelatin hydrogel. The gelatin hydrogel incorporating HGF induced VEGF around the implanted site. In vitro bioassay revealed that HGF molecules interacting with gelatin, still exhibited the biological activity. The interacted HGF would be released from gelatin hydrogels only when they were degraded to generate water-soluble gelatin fragments. It is possible that the HGF associating gelatin fragments of bioactivating, results in induced angiogenic effect.

Animals↗
PubMed1999

Synthesis of superporous hydrogels: hydrogels with fast swelling and superabsorbent properties.

We have been interested in the synthesis of hydrogels with fast swelling kinetics and superabsorbent properties. To increase the water absorption rate, interconnected pores were introduced to the hydrogels. Since the pore size in the dried hydrogels is in the order of hundreds of micrometers, these hydrogels are called "superporous" hydrogels. Superporous hydrogels were synthesized by crosslinking polymerization of various vinyl monomers in the presence of gas bubbles formed by the chemical reaction of acid and NaHCO3. The polymerization process was optimized to capture the gas bubbles inside the synthesized hydrogels. The use of the NaHCO3/acid system allowed easy control of timing for gelation and foam formation. We found that PF127 was the best foam stabilizer for most of the monomer systems used in our study. Scanning electron microscope (SEM) pictures showed interconnected pores forming capillary channels. The capillary channels, which were critical for fast swelling, were preserved during drying by dehydrating water-swollen hydrogels with ethanol before drying. The ethanol-dehydrated superporous hydrogels reached equilibrium swelling within minutes. The equilibrium swelling time could be reduced to less than a minute with the use of a wetting agent. In our study, water moisture was used as a wetting agent since the amount of moisture content in the dried hydrogels easily could be controlled. Preparation of superporous hydrogels using the right blowing system, foam stabilizer, drying method, and wetting agent makes it possible to reduce the swelling time to less than a minute regardless of the size of the dried gels. The superporous hydrogels can be used where fast swelling and superabsorbent properties are critical.

Absorption↗
PubMed2004

The characteristics of spontaneously forming physically cross-linked hydrogels composed of two water-soluble phospholipid polymers for oral drug delivery carrier I: hydrogel dissolution and insulin release under neutral pH condition.

Hydrogels bearing a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine (MPC), were prepared from two aqueous solutions of polymers, water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB). The hydrogel, which was formed by physical cross-linking spontaneously without any chemical reactions and/or any physical stimuli, showed a controllable insulin release through a pH change in the medium by changing the hydrogen bonds. In this study, the mechanical strength, erosion of the hydrogel caused by polymer dissociation, and the release of insulin were examined with attention to the following three parameters of the MPC polymer: molecular weight of the polymers, composition of PMA and PMB (PMA/PMB ratio), and polymer concentration inside the hydrogel. The hydrogel with the highest mechanical strength was obtained at a PMA/PMB ratio = 3/7 (v/v, by volume ratio) while the hydrogel with the slowest dissolution was obtained at a ratio of 5/5 (v/v). The release was in good match with the dissolution and followed anomalous transport for all, but the diffusion exponent n changed according to the PMA/PMB ratio. An increase in the polymer concentration inside the hydrogel caused an increase in the mechanical strength of the hydrogel. When the polymer concentration was more than 20 wt.%, the absorption of water under neutral pH condition (pH 6.8) was observed. The release of insulin was suppressed below 10% during the swelling process of the hydrogel under neutral pH condition, while release was accelerated during the erosion process of the hydrogel. The relationship between erosion of the hydrogel and the release of the insulin depended on the erosion process of the hydrogel but differed according to the PMA/PMB ratio.

Administration, Oral↗
PubMed2005

Dependence of copolymer composition, swelling history, and drug concentration on the loading of diltiazem hydrochloride (DIL.HCl) into poly[(N-isopropylacrylamide)-co-(methacrylic acid)] hydrogels and its release behaviour from hydrogel slabs.

The loading of an antihypertensive cationic drug, diltiazem hydrochloride (DIL.HCl), into poly(N-isopropylacrylamide) [P(N-iPAAm)], poly(methacrylic acid) [P(MAA)], and their poly[(N-isopropylacrylamide)-co-(methacrylic acid)] P[(N-iPAAm)-co-(MAA)] hydrogels as well as their release behaviour have been investigated. For this purpose, two series of hydrogels have been tested, one previously soaked under acidic pH (treated hydrogels) and the other from the synthesis and washed in deionized water (untreated hydrogels). For the drug loading, these two series of hydrogels have been soaked in drug solutions with different concentrations. DIL.HCl amounts loaded by the gels as well as swelling degrees as a function of both hydrogel composition and DL.HCl concentration in the loading solution have been analyzed. Due to the interactions among DIL.HCl and the MAA group, "untreated" enriched MAA copolymer hydrogels present the highest drug load and loading efficiency. A DIL.HCl concentration of 320 microm/mL has been employed to load copolymers for release experiments, because for this concentration, hydrogels reach relative high drug load with a still high efficiency of loading. Release has been tested in three media, namely, fresh water (Milli-Q grade, pH 7.0), 0.1 N hydrogen chloride (pH 1.2), and a phosphate buffer (pH 7.0). In general, release is lower in fresh water and acidic media than in phosphate buffer. To explain these results, the effect of temperature, medium, and composition on the pH and thermo sensitivity of the hydrogels as well as the diltiazem-polymer interactions have been taken into account.

Acrylamides↗
PubMed2006

Using a kinase/phosphatase switch to regulate a supramolecular hydrogel and forming the supramolecular hydrogel in vivo.

We have designed and synthesized a new hydrogelator Nap-FFGEY (1), which forms a supramolecular hydrogel. A kinase/phosphatase switch is used to control the phosphorylation and dephosphorylation of the hydrogelator and to regulate the formation of supramolecular hydrogels. Adding a kinase to the hydrogel induces a gel-sol phase transition in the presence of adenosine triphosphates (ATP) because the tyrosine residue is converted into tyrosine phosphate by the kinase to give a more hydrophilic molecule of Nap-FFGEY-P(O)(OH)(2) (2); treating the resulting solution with a phosphatase transforms 2 back to 1 and restores the hydrogel. Electron micrographs of the hydrogels indicate that 1 self-assembles into nanofibers. Subcutaneous injection of 2 in mice shows that 80.5 +/- 1.2% of 2 turns into 1 and results in the formation of the supramolecular hydrogel of 1 in vivo. This simple biomimetic approach for regulating the states of supramolecular hydrogels promises a new way to design and construct biomaterials.

Adenosine Triphosphate↗
PubMed2001

On the release of proteins from degrading dextran methacrylate hydrogels and the correlation with the rheologic properties of the hydrogels.

PURPOSE: To study the release of macromolecules of different sizes (bovine serum albumin, immunoglobulin G) from degrading (addition of dextranase) dextran methacrylate (dex-MA) hydrogels and to correlate the release with the evolution of the rehologic properties of the hydrogels during degradation. METHODS: The size of the macromolecules, the degree of substitution (i.e., number of methacrylates per 100 glycopyranose residues) of the dex-MA and the dextranase concentration in the hydrogels was varied. The rheologic properties were measured with a controlled stress rheometer. RESULTS: The release from dex-MA hydrogels without dextranase was very small [7-20% (time frame up to 180 days)] showing that most of the molecules were entrapped within the hydrogel network. The release from degrading dex-MA hydrogels followed zero-order kinetics for all molecules during a substantial period of the release. This was explained by a liberation and an increasing diffusivity of the proteins in the course of the degradation. The total amount released and the release rates could be well correlated with the rheologically observed degradation rates. CONCLUSIONS: It was shown that rheology can be a useful tool to help explain the release from degrading hydrogels.

Dextranase↗
PubMed2004

Changes in myopia with low-Dk hydrogel and high-Dk silicone hydrogel extended wear.

PURPOSE: This study compared changes in myopia between wearers of high-oxygen permeability (Dk) silicone hydrogel lenses and low-Dk hydrogel lenses after 1 year of extended wear (EW). METHODS: Ninety-two adult subjects were randomly assigned to a lens type. Subjective refraction and autokeratometry were performed at baseline and at 6 and 12 months. RESULTS: After 6 months of EW, myopia (spherical equivalent) regressed by 0.18 +/- 0.33 D (p < 0.001) in the high-Dk silicone hydrogel group and progressed by -0.23 +/- 0.36 D (p < 0.001) in the low-Dk hydrogel group. There were no further changes after 12 months. Previous lens wear history, baseline refractive error, and age and gender did not have an impact on the change in myopia, and only 35% of the variation could be accounted for by changes in corneal curvature and lens type. CONCLUSION: Soft contact lens type significantly affects the direction of change in myopia during EW. We hypothesize that these changes are driven by pressure-related redistribution of corneal tissue in high-Dk silicone hydrogel lens wearers and by hypoxia-associated corneal thinning in low-Dk hydrogel wearers. More long-term studies are required to confirm whether the effects of high-Dk silicone hydrogel lens wear on myopia are permanent.

Adult↗
PubMed2004

[Hydrogels: properties and application in the technology of drug form. II. Possibilities of use of hydrogels as active substance carriers].

In first unit of running was described the properties, method the obtention and kinds sensitive on factors such how the temperature, pH, the electrolytes, the chosen substances, light, of hydrogels and hydrogel delivery systems. The following study is a review of literature related to application of hydrogel as healing substances carriers, possibility of application of hydrogels in oral, applied on skin and the rectal, vaginal systems of release, applied on nasal as well as passed to eyes and parenteral. The utilization the hydrogels in construction the new systems of release the substance allows to remain the aspect ratio time of substance at the application place, the obtainment of prolonged release the medicine, by parallel of applied dose and the system undesirable effects. The hydrogels on the basis of were received the form of medicine about controlled release the substance, bioadhesive drug carriers as well targetable devices of therapeutic agents.

Administration, Cutaneous↗
PubMed2002

In vitro evaluation of the dehydration characteristics of silicone hydrogel and conventional hydrogel contact lens materials.

PURPOSE: This study investigated the in vitro dehydration performance of silicone hydrogel and conventional hydrogel contact lens materials. METHODS: In vitro dehydration was assessed using a gravimetric method. The mass loss over time of Focus Night&Day, PureVision, Optima, Acuvue and Proclear Compatibles was measured as the ambient temperature increased from room temperature to 34 degrees C under varying airflow and humidity conditions. RESULTS: Dehydration data demonstrated a typical ogival form. The results were best fitted with a double exponential, non-linear regression model, which accounted for at least 99% of the variance. Regardless of material, increased airflow had a greater impact on dehydration rate than increased humidity (P<0.05). Relative dehydration amounts were strongly correlated with initial water content (r(2)=0.92), with higher water content materials dehydrating to a greater extent. CONCLUSIONS: In vitro dehydration studies of conventional and novel silicone-containing hydrogel materials indicated that evaporation rates from materials are predominantly water content related, with only subtle differences between materials of similar water contents being seen. Environmental conditions have a significant impact on in vitro dehydration, with increased airflow having a greater impact than reduced humidity on increasing dehydration rates. In vitro dehydration is closely related to bulk water diffusion rates and, as a result of their low water content, silicone-containing hydrogel materials exhibit low levels of dehydration compared with high water content hydrogel contact lens materials. Further, in vivo studies are necessary to see if the in vitro dehydration behaviour of silicone hydrogel materials is predictive of in-eye performance.

Journal Article↗
PubMed1989

Synthetic hydrogels. VI. Hydrogel composites as wound dressings and implant materials.

An overview is presented of the use of hydrogel composites as biomaterials. These range from laminates or coatings (in which a homogeneous hydrogel is used in conjunction with a more mechanically stable substrate), through blends of hydrogels with synthetic hydrophobic polymers, to the use of two-component systems in which water enhances the compatibility of two structurally different polymers. Although synthetic hydrogels provide an ideal basis for materials of these types, naturally occurring hydrophilic polymers with their unique properties have a major contribution to make. It is in the clinical and patent literature, rather than journals dealing with polymers per se, that the vast majority of examples of the use of hydrogel composites are found. This review collects and comments on examples based on synthetic developments in this field during the last decade, particularly in relation to the development of wound dressings and implant materials.

Bandages↗
PubMed2004

Characterization of the surface of conventional hydrogel and silicone hydrogel contact lenses by time-of-flight secondary ion mass spectrometry.

PURPOSE: To characterize the surfaces of unworn conventional hydrogel and silicone hydrogel contact lenses. METHODS: Near-identical formulations of poly(hydroxyethyl methacrylate) (pHEMA) were used to manufacture lathe-cut, spun-cast, and cast-molded contact lenses. The surfaces of two of each of these lens types and two of each of two commercially available silicone hydrogel lenses-balafilcon A (PureVision) and lotrafilcon A (Focus Night and Day)-were analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). RESULTS: The ToF-SIMS spectra revealed the presence of the bulk polymer pHEMA at the surface of all three hydrogel lenses, along with other contaminants, such as poly(dimethyl siloxane), alkyl sulfates, alkyl-aryl sulfonates, dioctyl phthalate, Irgafos 168, sodium, chlorine, aluminum, potassium, calcium, copper, and fluorine, which are primarily derived from the various processing steps undertaken in lens manufacture, handling, and storage. The amount of bulk polymer detected at the surface of the PureVision lens was greater than that detected at the surface of the Night and Day lens. In addition, contaminants similar to those found on the surfaces of the conventional hydrogel lenses were detected. The Focus Night and Day lens appears to be coated with an organo-nitrogen material, which results from the plasma deposition of reactive precursors on the surface. CONCLUSIONS: We confirm that ToF-SIMS has the capacity to characterize the surface chemistry of contact lenses. The ongoing application of this technique can assist researchers and clinicians to understand the clinical performance of contact lenses.

Contact Lenses, Hydrophilic↗
PubMed2006

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 4: growth of rat bone marrow stromal cells in three-dimensional hydrogels with positive and negative surface charges and in polyelectrolyte complexes.

The growth of bone marrow stromal cells was assessed in vitro in macroporous hydrogels based on 2-hydro- xyethyl methacrylate (HEMA) copolymers with different electric charges. Copolymers of HEMA with sodium methacrylate (MA(-)) carried a negative electric charge, copolymers of HEMA with [2-(methacryloyloxy)ethyl] trimethylammonium chloride (MOETA(-)) carried a positive electric charge and terpolymers of HEMA, MA(-) and MOETA(+) carried both, positive and negative electric charges. The charges in the polyelectrolyte complexes were shielded by counter-ions. The hydrogels had similar porosities, based on a comparison of their diffusion parameters for small cations as measured by the real-time tetramethylammonium iontophoretic method of diffusion analysis. The cell growth was studied in the peripheral and central regions of the hydrogels at 2 hours and 2, 7, 14 and 28 days after cell seeding. Image analysis revealed the highest cellular density in the HEMA-MOETA(+) copolymers; most of the cells were present in the peripheral region of the hydrogels. A lower density of cells but no difference between the peripheral and central regions was observed in the HEMA-MA(-) copolymers and in polyelectrolyte complexes. This study showed that positively charged functional groups promote the adhesion of cells.

Animals↗
PubMed2005

Bacterial populations on silicone hydrogel and hydrogel contact lenses after swimming in a chlorinated pool.

PURPOSE: A number of reports have indicated an association between swimming with contact lenses and subsequent eye infection. This study tests whether a hydrophilic contact lens worn while swimming accumulates bacteria present in the water. It was of interest to determine whether lens type (silicone hydrogel vs. hydrogel) affected the result. METHODS: Fifteen healthy noncontact lens wearers swam for 30 minutes with a silicone hydrogel lens (PureVision, Bausch & Lomb, Rochester, NY) on one eye and a hydrogel lens (Acuvue 2, Vistakon Inc., Jacksonville, FL) on the other. Lenses were removed aseptically and placed in sterile vials 10 minutes after the subjects left the water. Microbial growth was enumerated for total numbers of colonies and categorized by species present. Numbers of colonies were compared between the two lens groups and with a water sample taken from the pool at the time of the experiment. Eight of the subjects returned on a different day and wore new lenses for 50 minutes in normal room conditions. RESULTS: Two lenses were lost while swimming. Twenty-seven of the remaining 28 lenses worn while swimming showed colonization, principally with Staphylococcus epidermidis, which was also by far the most common species identified from the water itself. Small numbers of Staphylococcus aureus and Streptococcus salivarius were also present in the water and on the lenses. Numbers of colonies varied among subjects (range, 0 to 230), but no differences were observed between the two lens groups. Lenses removed after 30 minutes of wear without swimming were mostly sterile, with 3 of 16 lenses showing just two colonies each. CONCLUSION: It appears that wearing a hydrophilic lens while swimming allows accumulation of microbial organisms on or in the lens, regardless of lens material. Swimmers should be advised to wear tight-fitting goggles if lenses are worn while swimming, and thorough disinfection of the lenses before overnight wear seems prudent.

Bacteria↗
PubMed2005

Short-term adaptation of the human corneal endothelium to continuous wear of silicone hydrogel (lotrafilcon A) contact lenses after daily hydrogel lens wear.

PURPOSE: The purpose of this study is to assess whether improved oxygen availability to the cornea resulted in changes in the corneal endothelium. METHODS: Eighteen adult (average age 25.3 +/- 5.1 years) hydrogel lens wearers (average of 5.5 years prior daily lens wear, range 3-9 years) were refitted with silicone hydrogel lenses (Focus Night and Day) for continuous wear over 30 days and nights. They were assessed in detail immediately before the refit (baseline measures) and again after 6 months of wear with lens replacement every 30 days. Assessments included slit biomicroscopy (for grading of limbal and bulbar redness), corneal staining with fluorescein, and then by noncontact specular microscopy for central corneal thickness (CCT) and endothelial cell layer images. The endothelial images exported as JPEG files and printed at 7000x magnification. The cell-cell borders were marked and then the areas of an average of 255 cells/image measured with a digitizer pad in stream mode. The number of cell sides was also counted. RESULTS: After 6 months of silicone hydrogel lens wear, most subjects showed an improvement in mean bulbar (1.1 to 0.9) and limbal redness (1.0 to 0.6, p < 0.001) and epithelial fluorescein staining (0.5 to 0.3) grades, and the mean CCT values decreased slightly in most subjects (0.527 to 0.520 mm), although the decrease was not statistically significant (p = 0.565). The mean endothelial cell area also increased slightly (358 to 363 microm2; p nonsignificant [NS] = 0.701), whereas the mean coefficient of variation (COV) decreased slightly (30.2 to 29.1%, p NS = 0.357). The calculated mean endothelial cell density (ECD; area/1000000 microm2) also decreased slightly from 2821 to 2774 cells/mm, but this change also was not statistically significant (p = 0.620). However, the changes in ECD showed a very substantial relationship to the changes in CCT, i.e., as CCT decreased, so the apparent ECD decreased; this change was highly significant (r = 0.747, p < 0.001). This relationship was slightly stronger still when possible image magnification differences were corrected for. The percentage of six-sided ("hexagonal") cells increased slightly (58.3 to 60.1%). CONCLUSION: The results indicate that, in silicone hydrogel lens wearers exhibiting positive external eye signs thought to be associated with improved oxygen availability, subtle morphologic changes (marginally decreased polymegethism and pleomorphism) in the central region of the corneal endothelium can occur. It remains to be established, however, whether these changes can be directly attributed to oxygen effects (reduced hypoxia and hypercapnia altering the endothelial cells) or to a mechanical effect (in which changes in corneal thickness result in a reorganization of the corneal endothelium).

Adaptation, Physiological↗
PubMed2005

Histrelin Hydrogel Implant--Valera: Histrelin implant, LHRH-Hydrogel implant, RL 0903, SPD 424.

Valera Pharmaceuticals, formerly Hydro Med Sciences, is developing a once-yearly Histrelin Hydrogel Implant [Histrelin implant, LHRH-Hydrogel implant, RL 0903, SPD 424, Vantas], a subcutaneous (s.c.) reservoir device capable of long-term delivery of histrelin at constant release rates for the treatment of prostate cancer. Histrelin is a luteinising hormone-releasing hormone agonist (LHRH). A different formulation of the LHRH implant is currently in development for the treatment of central precocious puberty (CPP). On 4 September 2003, Hydro Med Sciences announced that it had changed its name to Valera Pharmaceuticals. Shire Pharmaceuticals had an option to market and distribute the histrelin implant outside the US, but in a realigned agreement announced in January 2002, Shire stated that HydroMed (now Valera) would be responsible for concluding the phase III studies, filing for regulatory approval and producing the implant, while also gaining marketing rights in the US. Shire has no further involvement in development, but retains an option to market and distribute the product outside the US. The product is available for rest-of-the-world licensing through Valera Pharmaceuticals' business development division. Paladin Labs has received the exclusive rights for the sale and marketing of histrelin hydrogel implant in Canada. Valera Pharmaceuticals will have the responsibility for manufacturing and completing development of the product. In July 2004, Paladin announced it had filed for regulatory approval with Health Canada for the treatment of prostate cancer. Phase III trials have been conducted and initially involved two open-labelled, randomised, parallel studies that compared the hydrogel implant with the active comparators, leuprorelin acetate 22.5 mg depot (TAP Pharmaceutical's Lupron Depot) and a 3-month implant of goserelin acetate (Astra Zeneca's Zoladex). However, because of financial constraints, HydroMed discontinued recruitment in a phase II European study and could not rationalise keeping the comparator arm of the phase III study. The US FDA then gave permission to continue the US part of the programme without the comparator arm, but with appropriate increases in the patient sample size. Patient enrolment in the phase III trial (US and Canada) was completed in July 2002. Valera Pharmaceuticals believes the product may have advantages over standard prostate cancer treatments including reduced costly surgical procedures, lower dosing, increased patient compliance and peace-of-mind, as well as potentially less cost to the patient. The phase III studies were completed in the second half of 2003.CPP arises from the increased release by the pituitary gland hormone gonadotropins and is characterised by an early onset of sexual development in pre-adolescents. Currently, the treatment of CPP involves injections of synthetic gonadotropic hormone-releasing factor agonists such as Supprelin (histrelin acetate) and TAP Pharmaceutical's Lupron Depot-Red (leuprolide acetate) every 28 days, a potentially painful procedure. This treatment inhibits pituitary release of gonadotropins. Valera's histrelin implant is a compact, removable subcutaneous implant that can be applied under a local anaesthetic in doctor's surgery.

Antineoplastic Agents↗