An examination of the thermorheological and drug release properties of zinc tetraphenylporphyrin-containing thermoresponsive hydrogels, designed as light activated antimicrobial implants

This study describes the thermorheological, mechanical and drug release properties of novel, light-activated antimicrobial implants. Hydrogels, based on N-isopropylacrylamide (NIPAA) and hydroxyethyl methacryl ate (HEMA) and either devoid of or containing zinc tetraphenylporphyrin, were prepared by free radical polymerisation and characterised using oscillatory rheometry and texture profile analysis. Drug release was studied at both 20 and 37 degrees C. Hydrogels containing NIPAA exhibited a sol-gel temperature (Tin), which increased as the proportion of HEMA increased and was

Novel, antibacterial silicone biomaterials for the prevention of microbial adherence and infection in urinary catheters

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Size-fitting of Intravaginal Rings for Macaques and in vitro Release Kinetics of Zinc Finger Inhibitors

Background: Small molecule inhibitors of the zinc finger domain (ZFI) in the nucleocapsid protein (NCp7) of HIV-1 are potent inhibitors of HIV and SIV
replication and may have utility as topical products to prevent infection. Furthermore, intravaginal rings (IVRs) were developed as coitally-independent,
sustained release devices which could be used for administration of HIV microbicides. The aims of these studies were to demonstrate that IVRs sized for
macaques are practical and compatible with the current generation of thioester-based NCp7 inhibitors.

Methods: Non-medicated silicone elastomer vaginal rings of various sizes thought to be applicable for macaques were prepared and tested for vaginal fit in Pigtailed and Chinese Rhesus macaques. Macaques were monitored for 8 weeks for mucosal disruption by colposcopy and proinflammatory cytokine markers in cervical vaginal lavages (CVL) using Luminex bead-based technology. Three different ZFIs (compounds 52, 89 and 122, each derived from an N-substituted S-acyl-2-mercaptobenzamide thioester scaffold) were loaded at 50 mg into an optimal matrix-type ring design. In vitro continuous release studies were then conducted over 28 days and analyzed by HPLC. Rate of release was determined by linear regression analysis.

Results: Qualitative evaluation at the time of ring insertion suggested that the 25 mm ring provided optimal fit in both macaque species. All rings remained in
place during the study period (2 to 4 weeks), and the animals did not attempt to remove the rings. No tissue irritation was observed, and no signs of physical
discomfort were noted. Also, no significant induction of cervicovaginal proinflammatory markers was observed during the 8-week period during and following ring insertion. One Pigtailed macaque showed elevated IL-8 levels in the CVL during the period when the ring was in place; however, these levels were comparable to those observed in two control macaques. In vitro release of the ZFIs peaked at day 1 and then continually declined to near steady-state rates between 20-30 mcg/day. The percent release after 14 days was 2.9, 2.0 and 0.9 for ZFI 89, 52 and 122, respectively.

Conclusions: IVRs of 25mm diameter, determined to be the optimal size for macaques, were well tolerated and did not induce inflammation. Release of all ZFI compounds followed t 0.5 kinetics. These findings suggest that efficacy testing in primate models is warranted to fully evaluate the potential to prevent
transmission.

Infection-Responsive Drug Delivery from Urinary Biomaterials Controlled by a Novel Kinetic and Thermodynamic Approach

Purpose. The pH-dependent physicochemical properties of the antimicrobial quinolone, nalidixic acid, were exploited to achieve ‘intelligent’ drug release from a potential urinary catheter coating, poly(2-hydroxyethylmethacrylate) (p(HEMA)), in direct response to the elevated pH which occurs at the onset of catheter infection.
Methods. p(HEMA) hydrogels, and reduced-hydrophilicity copolymers incorporating methyl methacrylate, were loaded with nalidixic acid by a novel, surface particulate localization method, and characterized in terms of pH-dependent drug release and microbiological activity against the common urease-producing urinary pathogen Proteus mirabilis.
Results. The pH-dependent release kinetics of surface-localized nalidixic acid were 50- and 10-fold faster at pH 9, representing the alkaline conditions induced by urease-producing urinary pathogens, compared to release at pH 5 and pH 7 respectively. Furthermore, microbiological activity against P. mirabilis was significantly enhanced after loading surface particulate nalidixic acid in comparison to p(HEMA) hydrogels conventionally loaded with dispersed drug. The more hydrophobic methyl methacrylate-containing copolymers also demonstrated this pH responsive behavior, but additionally exhibited a sustained period of zero-order release.
Conclusions. The paradigm presented here provides a system with latent, immediate infection-responsive drug release followed by prolonged zero-order antimicrobial delivery, and represents an ‘intelligent’, infection-responsive, self-sterilizing biomaterial.

A comparison of the effects of ibuprofen and indomethacin upon renal haemodynamics and electrolyte excretion in the presence and absence of frusemide

1. This study has compared the effects of ibuprofen and indomethacin upon renal haemodynamics, electrolyte excretion and renin release in the presence and absence of frusemide under sodium replete conditions in eight healthy volunteers. 2. Neither ibuprofen (400 mg and 800 mg) nor indomethacin (50 mg) affected renal blood flow, glomerular filtration rate or electrolyte excretion in the basal state. 3. Frusemide had no effect on renal blood flow, but significantly increased glomerular filtration rate. This latter change was suppressed significantly only by ibuprofen 400 mg. Frusemide-induced diuresis was inhibited by all treatments, while natriuresis following frusemide was inhibited by indomethacin only. 4. Significant increments in plasma renin activity, which were suppressed by all treatments, were observed after frusemide. The degree of inhibition of the renin responses was significantly greater in the presence of indomethacin than with either dose of ibuprofen. 5. In a sodium replete setting in healthy volunteers, indomethacin and ibuprofen had no detrimental effects on basal renal function. In the presence of frusemide, indomethacin had more anti-natriuretic and renin-suppressing effect than ibuprofen. There was no evidence for a dose-related effect of ibuprofen.

The effects of cilazapril alone and in combination with frusemide in healthy subjects

1. In a fourway double-blind placebo controlled study, the effects of cilazapril, a new angiotensin converting enzyme inhibitor, on renal function and the responses to intravenous frusemide were studied in a group of twelve salt depleted male volunteers. 2. Cilazapril produced an increase in effective renal plasma flow and urinary output of prostaglandin E2 metabolite (PGE2-M) but no effect on sodium, potassium or water excretion. 3. Pretreatment with cilazapril antagonised the effects of frusemide on glomerular filtration, PGE2-M and sodium excretion.

Sonochemical synthesis and measurement of optical properties of zinc sulfide quantum dots

A facile sonochemical method has been developed to prepare very small zinc sulfide nanoparticles (ZnS NPs) of extremely small size about 1. nm in diameter using a set of ionic liquids based on the bis (trifluoromethylsulfonyl) imide anion and different cations of 1-alkyl-3-methyl-imidazolium. The structural features and optical properties of the NPs were determined in depth with X-ray powder diffraction (XRD), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS) analysis, and UV-vis absorption spectroscopy. The energy band gap measurements of ZnS NPs were calculated by UV-vis absorption spectroscopy. One of the interesting features of the present work is that the wide band gap semiconductor ZnS nanocrystals were prepared which are used in the fabrication of photonic devices.