Heavier-than-water silicone oil mixture as a long-term tamponade agent:A pilot study

Purpose: To evaluate the tamponade effect on the retina of a heavier-than-water silicone oil mixture and to compare it with the effect of silicone oil. Methods: Prospective, non-randomised, comparative pilot study. Phakic/pseudophakic patients with retinal detachment undergoing vitrectomy with Densiron 68 or silicone oil were recruited. The 'separation volume', defined as the relative volume of the space between intraocular tamponade agent and retina, was estimated using magnetic resonance imaging in both groups and compared. Results: Nine participants were included; 4 received silicone oil and 5 Densiron 68. The mean separation volume was statistically significantly larger in the silicone oil group (0.477 ± 0.419 cm ) than in the Densiron group (0.042 ± 0.013 cm ; p = 0.014). Conclusions: In this study Densiron achieved an excellent tamponade effect in the retina. © 2011 S. Karger AG, Basel.

Pseudo-endothelial dystrophy associated with emulsified silicone oil

Purpose. To describe endothelial changes associated with emulsified silicone oil. Methods. Report of a case. Results. A 77-year-old man had multiple and diffuse clear vesicles on the endothelium of his left eye (LE). The cornea was clear and thin. He had undergone pars plana vitrectomy and intraocular silicone oil injection 5 years before presentation. Specular microscopy revealed numerous small bubbles of emulsified silicone oil and a mild degree of endothelial damage. Conclusion. Emulsified silicone oil can adhere to the endothelium and induce an apparent droplet-like endotheliopathy.

Hard coatings on elastomers for reduced permeability and increased wear resistance

In this study, three different elastomers, namely hydrogenated nitrile butadiene rubber, fluoroelastomer and silicone, have been subjected to two different hard metallised coatings by ion implantation process. The three different elastomers are commonly used in various seal applications, where reduced wear and gas permeability are essential in maintaining seal performance and functionality. Samples of these rubbers have been coated with chromium coating in one set of tests. In the second set of tests, samples of elastomers have been coated with tungsten carbide coating being deposited on all the three different elastomers. Wear, gas permeability and mechanical behaviour of the coated samples were compared with each other and with the control uncoated elastomers. All the coated samples showed good reduction in gas permeability. With the use of metallised coatings, there has been improved resistance to wear in all the coated samples. Adhesion strength and effect of coating on the elastomer have been investigated by mechanical testing. Mechanical tests revealed good adhesion of metal coatings on all the rubber samples, and there was no detrimental effect on the mechanical properties after coating. © 2012 Institute of Materials, Minerals and Mining.

Effectiveness of diode laser trans-scleral cyclophotocoagulation in patients following silicone oil-induced ocular hypertension in Chinese eyes.

We evaluated the effectiveness of diode laser trans-scleral cyclophotocoagulation (TSCPC) on intraocular pressure (IOP) in nine patients having raised IOP following use of silicone oil (SO) for retinal detachment (RD) surgery in a retrospective observational case series. Diode laser TSCPC was applied at a power setting of 1.75 to 2.5 watts, for two sec with a maximum of 30 applications. The patients were followed up for 40 to 312 weeks. The mean pre-laser IOP was 32.06 mm Hg (SD 7.32). The mean post-laser IOP at one month, three months and six months was 17.89 mm Hg (SD 8.23), 21.89 mm Hg (SD 8.16) and 21.67 mm Hg (SD 7.55) respectively. The final IOP (at the last follow-up) was 19.56 mm Hg (SD 7.85) (P=0.021). Seven of them had undergone SO removal. In our observation, effectiveness of TSCPC in long-term control of SO-induced ocular hypertension was limited as compared to short-term control of IOP.

Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide

TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor that is presently being developed as a vaginal HIV microbicide. To date, most vaginal microbicides under clinical investigation have been formulated as single-dose semi-solid gels, designed for application to the vagina before each act of intercourse. However, a clear rationale exists for providing long-term, controlled release of vaginal microbicides in order to afford continuous protection against heterosexually transmitted HIV infection and to improve user compliance. In this study we report on the incorporation of various pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal rings (IVRs) in order to modify the controlled release characteristics of the microbicide. The results demonstrate that TMC 120 is released in zero-order fashion from the rings over a 28-day period and that release parameters could be modified by the inclusion of release-modifying excipients in the IVR. The hydrophobic liquid excipient isopropyl myristate had little effect on steady-state daily release rates, but did increase the magnitude and duration of burst release in proportion to excipient loading in the IVR. By comparison, the hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release parameters. A hydrophilic excipient, lactose, had the surprising effect of decreasing TMC 120 burst release while increasing the apparent steady-state daily release in a concentration-dependent manner. Based on previous cell culture data and vaginal physiology, TMC120 is released from the various ring formulations in amounts potentially capable of maintaining a protective vaginal concentration. It is further predicted that the observed release rates may be maintained for at least a period of 1 year from a single ring device. TMC 120 release profiles and the mechanical properties of rings could be modified by the physicochemical nature of hydrophobic and hydrophilic excipients incorporated into the IVRs.

Novel biomimetic and bioactive silicones

The features and potential applications of a novel silicone for constructing or coating medical devices are described. The platform technology that has been developed reportedly overcomes inherent problems with existing silicone devices and allows drug delivery from devices employing the material.

Relationship between biomedical catheter surface properties and lubricity as determined using textural analysis and multiple regression analysis

In this study, the surface properties of and work required to remove 12 commercially available and developmental catheters from a model biological medium (agar), a measure of catheter lubricity, were characterised and the relationships between these properties were examined using multiple regression and correlation analysis. The work required for removal of catheter sections (7 cm) from a model biological medium (1% w/w agar) were examined using tensile analysis. The water wettability of the catheters were characterised using dynamic contact angle analysis, whereas surface roughness was determined using atomic force microscopy. Significant differences in the ease of removal were observed between the various catheters, with the silicone-based materials generally exhibiting the greatest ease of removal. Similarly, the catheters exhibited a range of advancing and receding contact angles that were dependent on the chemical nature of each catheter. Finally, whilst the microrugosities of the various catheters differed, no specific relationship to the chemical nature of the biomaterial was apparent. Using multiple regression analysis, the relationship between ease of removal, receding contact angle and surface roughness was defined as: Work done (N mm) 17.18 + 0.055 Rugosity (nm)-0.52 Receding contact angle (degrees) (r = 0.49). Interestingly, whilst the relationship between ease of removal and surface roughness was significant (r = 0.48, p = 0.0005), in which catheter lubricity increased as the surface roughness decreased, this was not the case with the relationship between ease of removal and receding contact angle (r = -0.18, p > 0.05). This study has therefore uniquely defined the contributions of each of these surface properties to catheter lubricity. Accordingly, in the design of urethral catheters. it is recommended that due consideration should be directed towards biomaterial surface roughness to ensure maximal ease of catheter removal. Furthermore, using the method described in this study, differences in the lubricity of the various catheters were observed that may be apparent in their clinical use. (C) 2003 Elsevier Ltd. All rights reserved.

Evaluation of a poly(vinyl pyrollidone)-coated biomaterial for urological use

The associated problems of bacterial biofilm formation and encrustation that may cause obstruction or blockage of urethral catheters and ureteral stents often hinders the effective use of biomaterials within the urinary tract. In this in vitro study, we have investigated the surface properties of a hydrophilic polyvinyl pyrollidone) (PVP)-coating applied to polyurethane and determined its suitability for use as a urinary tract biomaterial by comparing its lubricity and ability to resist bacterial adherence and encrustation with that of uncoated polyurethane and silicone. The PVP-coated polyurethane was significantly more hydrophilic and more lubricious than either uncoated polyurethane or silicone. Adherence of a hydrophilic Escherichia coli isolate to PVP-coated polyurethane and uncoated polyurethane was similar but significantly less than adherence to silicone. Adherence of a hydrophobic Enterococcus faecalis isolate to PVP-coated polyurethane and silicone was similar but was significantly less than adherence to uncoated polyurethane. Struvite encrustation was similar on the PVP-coated polyurethane and silicone but significantly less than on uncoated polyurethane. Furthermore, hydroxyapatite encrustation was significantly less on the PVP-coated polyurethane than on either uncoated polyurethane or silicone. The results suggest that the PVP-coating could be useful in preventing complications caused by bacterial biofilm formation and the deposition of encrustation on biomaterials implanted in the urinary tract and, therefore, warrants further evaluation. (C) 2002 Elsevier Science Ltd. All rights reserved.

Multi-Study Assessment of Vaginal Cytokines and Microflora in the Safety Evaluation of Intravaginal Rings in Pig-Tailed Macaques

BACKGROUND: HIV microbicide trials have emphasized the need to evaluate the safety of topical microbicides and delivery platforms in an animal model prior to conducting clinical efficacy trials. An ideal delivery device should provide sustainable and sufficient concentrations of effective products to prevent HIV transmission while not increasing transmission risk by either local mucosal inflammation and/or disruption of the normal vaginal microflora.

METHODS: Safety analyses of macaque-sized elastomeric silicone and polyurethane intravaginal rings (IVRs) loaded with candidate antiretroviral (ARV) drugs were tested in four studies ranging in duration from 49 to 73 days with retention of the IVR being 28 days in each study. Macaques were assigned to 3 groups; blank IVR, ARV-loaded IVR, and naïve. In sequential studies, the same macaques were used but rotated into different groups. Mucosal and systemic levels of cytokines were measured from vaginal fluids and plasma, respectively, using multiplex technology. Changes in vaginal microflora were also monitored. Statistical analysis (Mann-Whitney test) was used to compare data between two groups of unpaired samples (with and without IVR, and IVR with and without ARV) for the groups collectively, and also for individual macaques.

RESULTS: There were few statistically significant differences in mucosal and systemic cytokine levels measured longitudinally when the ring was present or absent, with or without ARVs. Of the 8 proinflammatory cytokines assayed a significant increase (p = 0.015) was only observed for IL8 in plasma with the blank and ARV loaded IVR (median of 9.2 vs. 5.7 pg/ml in the absence of IVR). There were no significant differences in the prevalence of H2O2-producing lactobacilli or viridans streptococci, or other microorganisms indicative of healthy vaginal microflora. However, there was an increase in the number of anaerobic gram negative rods in the presence of the IVR (p= < 0.0001).

CONCLUSIONS: IVRs with or without ARVs neither significantly induce the majority of potentially harmful proinflammatory cytokines locally or systemically, nor alter the lactobacillus or G. vaginalis levels. The increase in anaerobic gram negative rods alone suggests minimal disruption of normal vaginal microflora. The use of IVRs as a long-term sustained delivery device for ARVs is promising and preclinical studies to demonstrate the prevention of transmission in the HIV/SHIV nonhuman primate model should continue.

Design, optimisation and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique.

PURPOSE:
Design and evaluation of a novel laser-based method for micromoulding of microneedle arrays from polymeric materials under ambient conditions. The aim of this study was to optimise polymeric composition and assess the performance of microneedle devices that possess different geometries.
METHODS:
A range of microneedle geometries was engineered into silicone micromoulds, and their physicochemical features were subsequently characterised.
RESULTS:
Microneedles micromoulded from 20% w/w aqueous blends of the mucoadhesive copolymer Gantrez® AN-139 were surprisingly found to possess superior physical strength than those produced from commonly used pharma polymers. Gantrez® AN-139 microneedles, 600 µm and 900 µm in height, penetrated neonatal porcine skin with low application forces (>0.03 N per microneedle). When theophylline was loaded into 600 µm microneedles, 83% of the incorporated drug was delivered across neonatal porcine skin over 24 h. Optical coherence tomography (OCT) showed that drug-free 600 µm Gantrez® AN-139 microneedles punctured the stratum corneum barrier of human skin in vivo and extended approximately 460 µm into the skin. However, the entirety of the microneedle lengths was not inserted.
CONCLUSION:
In this study, we have shown that a novel laser engineering method can be used in micromoulding of polymeric microneedle arrays. We are currently carrying out an extensive OCT-informed study investigating the influence of microneedle array geometry on skin penetration depth, with a view to enhanced transdermal drug delivery from optimised laser-engineered Gantrez® AN-139 microneedles.

Sustained release of proteins from a modified vaginal ring device

A new vaginal ring technology, the insert vaginal ring (InVR), is presented. The InVR overcomes the current shortfall of conventional vaginal rings (VRs) that are generally ineffectual for the delivery of hydrophilic and/or macromolecular actives, including peptides, proteins and antibodies, due to their poor permeation characteristics in the hydrophobic polymeric elastomers from which VRs are usually fabricated. Release of the model protein BSA from a variety of insert matrices for the InVR is demonstrated, including modified silicone rods, directly compressed tablets and lyophilised gels, which collectively provided controlled release profiles from several hours to beyond 4 weeks. Furthermore, the InVR was shown to deliver over 1 mg of the monoclonal antibody 2F5 from a single device, offering a potential means of protecting women against the transmission of HIV.