Punctal plug: a medical device to treat dry eye syndrome and for sustained drug delivery to the eye

Punctal plugs (PPs) are miniature medical implants that were initially developed for the treatment of dry eyes. Since their introduction in 1975, many PPs made from different materials and designs have been developed. PPs, albeit generally successful, suffer from drawbacks such as epiphora and suppurative canaliculitis. To overcome these issues intelligent designs of PPs were proposed (e.g. SmartPLUG™ and Form Fit™). PPs are also gaining interest among pharmaceutical scientists for sustaining drug delivery to the eye. This review aims to provide an overview of PPs for dry eye treatment and drug delivery to treat a range of ocular diseases. It also discusses current challenges in using PPs for ocular diseases.

A compact broadband ion beam focusing device based on laser-driven megagauss thermoelectric magnetic fields

Ultra-intense lasers can nowadays routinely accelerate kiloampere ion beams. These unique sources of particle beams could impact many societal (e.g., proton-therapy or fuel recycling) and fundamental (e.g., neutron probing) domains. However, this requires overcoming the beam angular divergence at the source. This has been attempted, either with large-scale conventional setups or with compact plasma techniques that however have the restriction of short (<1 mm) focusing distances or a chromatic behavior. Here, we show that exploiting laser-triggered, long-lasting (>50 ps), thermoelectric multi-megagauss surface magnetic (B)-fields, compact capturing, and focusing of a diverging laser-driven multi-MeV ion beam can be achieved over a wide range of ion energies in the limit of a 5° acceptance angle.

Semi-interpenetrating polymer networks incorporating polygalacturonic acid for medical device applications

Background Over 20 million people in the US are living with an implantable medical device [ADDIN RW.CITE{{3114 Higgins,DavidM 2009}}1], with similar figures anticipated for Europe. Complications in the use of medical implants include the Foreign Body Response (FBR) characterised by macrophage adherence and fusion, and device-related infection due to bacterial biofilm formationADDIN RW.CITE{{3124 Harding,JacquelineL 2014}}2. Both can have detrimental consequences on the structural and functional integrity of the medical device [ADDIN RW.CITE{{3101 Anderson,JamesM 2008; 3124 Harding,JacquelineL 2014}}2,3], often necessitating removal; a painful and expensive procedure [ADDIN RW.CITE{{3121 Mah,Thien-FahC 2001}}4]. Materials are sought to attenuate both the FBR and device-related infection, leading to medical devices with improved biocompatibility and performance. Objectives The present work involves development of a semi-interpenetrating network (SIPN) hydrogel containing polygalacturonic acid (PGA), a biopolysaccharide similar in structure to hyaluronic acid. We aim to synthesise, characterise and determine the in vitro biocompatibility of the developed SIPN. Results & Discussion We have successfully incorporated PGA into a poly(HEMA) based hydrogel, which shows favourable swelling and wettability. The surface topography appears altered in comparison to the control material, with pronounced micrometer-scale features. In terms of in vitro performance, the SIPN showed increased protein adsorption, and biofilm formation (Staphylococcus epidermidis and Escherichia coli, up to 1 Log CFU/sample greater than control). However the SIPN displayed minimal cytotoxicity towards L929 fibroblasts, and was resistant to the adherence of RAW 264.7 macrophages. Conclusions The PGA incorporated SIPN lacks cytotoxicity and shows reduced macrophage adherence, however the increased biofilm formation highlights a concern regarding possible device related infection in clinical use. Future work will focus on strategies to reduce bacterial adherence, while maintaining biocompatibility.

Empirical evaluation of multi-device profiling side-channel attacks

Side-channel analysis of cryptographic systems can allow for the recovery of secret information by an adversary even where the underlying algorithms have been shown to be provably secure. This is achieved by exploiting the unintentional leakages inherent in the underlying implementation of the algorithm in software or hardware. Within this field of research, a class of attacks known as profiling attacks, or more specifically as used here template attacks, have been shown to be extremely efficient at extracting secret keys. Template attacks assume a strong adversarial model, in that an attacker has an identical device with which to profile the power consumption of various operations. This can then be used to efficiently attack the target device. Inherent in this assumption is that the power consumption across the devices under test is somewhat similar. This central tenet of the attack is largely unexplored in the literature with the research community generally performing the profiling stage on the same device as being attacked. This is beneficial for evaluation or penetration testing as it is essentially the best case scenario for an attacker where the model built during the profiling stage matches exactly that of the target device, however it is not necessarily a reflection on how the attack will work in reality. In this work, a large scale evaluation of this assumption is performed, comparing the key recovery performance across 20 identical smart-cards when performing a profiling attack.

Anti-biofilm activity of ultrashort cinnamic acid peptide derivatives against medical device-related pathogens

The threat of antimicrobial resistance has placed increasing emphasis on the development of innovative approaches to eradicate multidrug-resistant pathogens. Biofilm-forming microorganisms, for example, Staphylococcus epidermidis and Staphylococcus aureus, are responsible for increased incidence of biomaterial infection, extended hospital stays and patient morbidity and mortality. This paper highlights the potential of ultrashort tetra-peptide conjugated to hydrophobic cinnamic acid derivatives. These peptidomimetic molecules demonstrate selective and highly potent activity against resistant biofilm forms of Gram-positive medical device-related pathogens. 3-(4-Hydroxyphenyl)propionic)-Orn-Orn-Trp-Trp-NH2 displays particular promise with minimum biofilm eradication concentration (MBEC) values of 125 µg/ml against methicillin sensitive (ATCC 29213) and resistant (ATCC 43300) S. aureus and activity shown against biofilm forms of Escherichia coli (MBEC: 1000 µg/ml). Kill kinetics confirms complete eradication of established 24-h biofilms at MBEC with 6-h exposure. Reduced cell cytotoxicity, relative to Gram-positive pathogens, was proven via tissue culture (HaCaT) and haemolysis assays (equine erythrocytes).

Existing in nature as part of the immune response, antimicrobial peptides display great promise for exploitation by the pharmaceutical industry in order to increase the library of available therapeutic molecules. Ultrashort variants are particularly promising for translation as clinical therapeutics as they are more cost-effective, easier to synthesise and can be tailored to specific functional requirements based on the primary sequence allowing factors such as spectrum of activity to be varied.

The potential of electron beam irradiation for simultaneous surface modification and bioresorption control of PLLA for medical device applications

Bioresorbable polymers have been widely investigated as materials exhibiting significant potential for successful application in the medical fields of bone fixation devices and drug delivery. Further to the ability to control degradation, surface engineering of polymers has been highlighted as a key method central to their development. Previous work has demonstrated the ability of electron beam (e-beam) technology to control the degradation profiles and bioresorption of a number of commercially relevant bioresorbable polymers (poly-l-lactic acid (PLLA), L-lactide/ DL-lactide co-polymer (PLDL) and poly(lactic-co-glycolic acid) (PLGA). This work investigates the further potential of e-beam technology to impart added biofunctionality through the manipulation of polymer (PLLA) surface properties. A Dynamatron Continuous DC e-beam unit (Synergy Health, UK), with beam energies of 0.5, 0.75, and 1.5 MeV, was used for the irradiation of PLLA samples with delivered surface doses of 150 or 500 kGy at each energy level. The chosen conditions reflect the need to achieve a specific surface modification for the control of surface degradation as demonstrated in previous work. Surface characterization was then performed using contact angle analysis, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and atomic force microscopy.
Results demonstrated a significant increase in surface wettability post e-beam treatment. In correlation with this, XPS data showed the introduction of oxygen-containing functional groups to the surface of PLLA. Raman spectroscopy indicated chain scission in the near surface region of PLLA. E-beam irradiation did not seem to affect the surface roughness of PLLA as a direct consequence of the treatment. In conclusion electron beam surface modification has been found to modify both the surface-to-bulk bioresorption profile and the surface hydrophilicity. Both could provide benefits in relation to the performance of implantable medical devices.

Improving antimicrobial release kinetics from hydrophobic polymer implants via ion pairing to combat biomedical-device related infection

Purpose The aim of this study is to improve the drug release properties of antimicrobial agents from hydrophobic biomaterials using using an ion pairing strategy. In so doing antimicrobial agents may be eluted and maintained over a sufficient time period thereby preventing bacterial colonisation and subsequent biofilm formation on medical devices. Methods The model antimicrobial agent was chlorhexidine and the selected fatty acid counter ions were capric acid, myristic acid and stearic acid. The polymethyl methacrylate films were loaded with 2% of fatty acid:antimicrobial agent at the following molar ratios; 0.5:1M, 1:1M and 2:1M and thermally polymerized using azobisisobutyronitrile initiator. Drug release experiments were subsequently performed over a 3-month period and the mass of drug released under sink conditions (pH 7.0, 37oC) quantified using a validated HPLC-UV method. Results In all platforms, a burst of chlorhexidine release was observed over the initial 24-hour period. Similar release kinetics were observed between the formulations during the initial 28 days. However, as time progressed, the chlorhexidine baseline plateaued after 56 days whereas formulations containing the counterions appeared to continuously elute linearly with time. As can be observed in figure 1, the rank order of total chlorhexidine release in the presence of 0.5M fatty acid was myristic acid (40%) > capric acid (35%) > stearic acid (30%)> chlorhexidine baseline (15%). Conclusion The incorporation of fatty acids within the formulation significantly improved chlorhexidine solubility within both the monomer and the polymer and enhanced the drug release kinetics over the period of study. This is attributed to the greater diffusivity of chlorhexidine through PMMA in the presence of fatty acids. In th absence of fatty acids, chlorhexidine release was facilitated by dissolution of surface associated drug particles. This study has illustrated the ability of fatty acids to modulate chlorhexidine release from a model biomaterial through enhanced diffusivity. This strategy may prove advantageous for improved medical devices with enhanced resistance to infection.

Lanthanide luminescent logic gate mimics in soft matter: [H(+)] and [F(-)] dual-input device in a polymer gel with potential for selective component release

The non-covalent incorporation of responsive luminescent lanthanide, Ln(iii), complexes with orthogonal outputs from Eu(iii) and Tb(iii) in a gel matrix allows for in situ logic operation with colorimetric outputs. Herein, we report an exemplar system with two inputs ([H(+)] and [F(-)]) within a p(HEMA-co-MMA) polymer organogel acting as a dual-responsive device and identify future potential for such systems.

Channel Measurements of Device-to-Device Communications at 2.45 GHz

In the future, device-to-device communications will become a fundamental part of cellular communications. Interoperability between handsets will be facilitated using frequencies located in a number of bands including those found in the Industrial, Scientific and Medical (ISM) band at 2.45 GHz. In this paper, we present the results of channel measurements made between two hypothetical cellular handsets operating at 2.45 GHz in an outdoor environment. We consider a range of typical usage scenarios such as both user equipment being held at the head while imitating a voice call, placed in user's pocket for both stationary and dynamic links. A range of parameter estimates obtained using the shadowed κ-μ fading model are also presented.