Micropore Technologies (United Kingdom)

This review explores the advancements in drug delivery systems that incorporate bile salts since bilosomes that were developed over 20 years ago. Bile salts, recognized for their unique amphiphilic properties, have emerged as versatile agents in enhancing solubility, stability, and bioavailability of various therapeutics. We discuss the innovative formulations developed, including micelles, liposomes, and nanoparticles, that leverage bile salts to facilitate targeted and sustained release. The review also highlights the mechanisms by which bile salts improve drug absorption, particularly for hydrophobic compounds, and examines the evolving regulatory landscape surrounding these systems. Furthermore, we address challenges faced in clinical translation and future directions for research, emphasizing the potential of bile salt-based systems in personalized medicine. Our evaluation highlights the significant role of bile salts in advancing drug delivery technologies and their promise for improving therapeutic outcomes.

In this work, novel fractal points have been introduced for EBI and results analysis in DRAM manufacturing that successfully boost signal resolution from within a die to a fractal point. With the implementation of the EBI recipe, the results show a significant improvement in nuisance defects reduction by 98.1%, as well as an increase in defects of interest (DOI) by 255.7%. Moreover, the Cohen’s d value of −1.32 indicates a substantial improvement in data discriminability. On the other hand, defect results with implementing fractal points demonstrate the new capabilities and value for microscopic EBI data analysis. With 10K-fold enhancement for resolution, specific weak region and defective probability for each unit can be identified. They provide new insights into evaluating die quality that indicate explicit direction to shorten the yield learning cycle and accelerate technology development prior to probe readings.

Despite the robust ability of microcapsules (MIC) to break and release agent for healing/sealing efficacy, the reduction of concrete strength has been a major issue when using MIC. In this study, the optimisation of concrete mix design was initiated with employing three main parameters: MIC size (56, 93 μm), MIC dosage (0, 3, 6% by weight of cement) and water-cement (w/c) ratio (0.40, 0.50, 0.60). The used microcapsules consisted of water repellent agent core acting as a sealing agent and polyurethane as the shell material. Results confirmed the MIC dosage as the most significant factor affecting the mechanical properties, while no significant effect on the MIC size. Further, the MIC effect can be reduced by changing the concrete mix design from low to high w/c. The sealing efficiency of concrete was remarkably improved with the inclusion of MIC and a good bond between the capsules and concrete matrix was attained.

Abstract Membrane emulsification has the potential to revolutionize the energy‐efficient production of uniform emulsions and dispersions, relevant to diverse fields from pharmaceutical active ingredient controlled release particles to Fast Moving Consumer Goods. A novel highly robust single‐pass continuous phase crossflow system has been developed providing dispersed phase concentrations up to 40% vol/vol and dispersed phase fluxes up to 5,730 L m−2 hr−1, from a single 100 mm long membrane tube. Extensive results of two oil‐in‐water systems (vegetable oil and PolyCaproLactone dissolved in DiChloroMethane) and one water‐in‐oil system (sodium silicate solution) are reported, using hydrophilic and hydrophobic membranes respectively. Mathematical models are validated enabling comprehensive engineering analysis of processes including predicted droplet size, membrane pressure drops, and energy requirement for dispersion production. Surfactant depletion, pore utilization, and droplet interaction at the membrane surface were investigated to provide a comprehensive analysis of the capabilities of novel annular‐flow membrane emulsification for high throughput emulsion generation.

Ketolides are a new class of antibacterials that have been specifically developed for the treatment of community-acquired respiratory tract infections in an era of increasing resistance among major etiologic pathogens. These agents possess several unique structural features, including a 3-keto function and a large aromatic side chain, that confer not only a mode of action that differentiates them from the macrolide class but also a reduced potential to induce--or select for--resistant strains. Studies also suggest that ketolides such as telithromycin have a lower ecologic impact on the body's microflora than agents such as clarithromycin and amoxicillin-clavulanate, potentially reducing the risk of emergence of resistant strains and the spread of such resistance to pathogenic species. Therefore, available evidence suggests that ketolides may not only provide important new treatment options in an era of increasing resistance but may also contribute to reducing the pressure for development of further resistance. Clearly, further studies are required to confirm this low resistance potential once the ketolide agents become more widely used in routine practice.

Of a total of 1043 macrolide-resistant Streptococcus pneumoniae isolates collected from 24 countries as part of PROTEKT 1999-2000, 71 isolates tested positive for both the mef(A) and erm(B) genes. Of 69 isolates subjected to further molecular investigations, all were resistant to tetracycline, 63 (91.3%) were resistant to penicillin, and 57 (82.6%) were resistant to trimethoprim-sulfamethoxazole. One isolate was also fluoroquinolone resistant, and another was resistant to quinupristin-dalfopristin. The ketolide telithromycin retained activity against all of the isolates. Of the 69 of these 71 isolates viable for further testing, 46 were from South Korea, 13 were from the United States, 8 came from Japan, and 1 each came from Mexico and Hungary. One major clonal complex (59 [85.5%] of 69 isolates) was identified by serotyping (with 85.5% of the isolates being 19A or 19F), pulsed-field gel electrophoresis, and multilocus sequence typing. The remaining isolates were less clonal in nature. Representative isolates were shown to carry the mobile genetic elements Tn1545 and mega, were negative for Tn1207.1, had tetracycline resistance mediated by tet(M), and contained the mef(E) variant of mef(A). All isolates were positive for mel, a homologue of the msr(A) efflux gene. These clones are obviously very efficient at global dissemination, and hence it will be very important to monitor their progress through continued surveillance. Telithromycin demonstrated high levels of activity (MIC for 90% of the strains tested, 0.5 micro g/ml; MIC range, 0.06 to 1 micro g/ml) against all isolates.

We investigated the in vitro development of fluoroquinolone resistance in Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae grown in McCoy cell monolayers in supplemented Eagle's minimum essential medium. With C. trachomatis, initial passages at sub-inhibitory fluoroquinolone concentrations did not affect fluoroquinolone susceptibility. However, after an initial lag of 10-24 passages (depending upon the fluoroquinolone used), fluoroquinolone resistance developed rapidly. The final fluoroquinolone MIC after a total of 30 passages was >256 times the MIC of the original wild-type strain with ofloxacin or ciprofloxacin passage. Analysis of the quinolone-resistance determining regions of two quinolone-resistant C. trachomatis mutants obtained after 30 passages showed that both isolates had a single serine to isoleucine substitution at amino acid position 83 in GyrA. In stark contrast, with C. pneumoniae no reduced fluoroquinolone susceptibility could be sustained, even after 30 passages with moxifloxacin or ofloxacin. With sparfloxacin passage, some indication of resistance was observed but no viable organisms could be isolated for further investigation. It is possible that fluoroquinolone-resistant C. pneumoniae are less able to survive than wild type, which may explain why resistance does not develop readily.

What has been the real contribution of molecular biology, i.e. recombinant DNA technology to human therapeutics? Like Brazil it will always have a great future! This book of essays on the first generation of protein drugs made by recombinant protein synthesis is a fascinating melange of gossip, science, history and opinion, covering the 20 or so years since human insulin was first introduced. Since then, 1982, we have had haemophiliac globulins, growth hormone, erythropoietin, colony stimulating factors, interferon and clot busters, all natural proteins or ‘first generation’ recombinant products. We can see how the sector has matured now that generic producers are setting up and much work has taken place to develop ‘improved’ synthetic versions of natural products. Now we look to a second generation of artificial or hybrid proteins such as immunocytokines or engineered thrombolytics. The essays on these subjects are all by distinguished participants in the various discovery/exploitation processes. This is recent history, sometimes told starchily, sometimes well. History always makes for a good read especially for those keen on repeating it. As usual, the path to new therapies is not a simple one. It started with technical difficulties and suffered the usual unexpected failures and compensatory successes. Who would have predicted that human insulin would be less well tolerated than pig insulin? Who would have seen recombinant erythropoietin as a ‘drug of abuse’ in the Tour de France? On the postitive side, the introduction of colony stimulating factors has improved the practice of oncology, enabling neutropenia induced by cytotoxic agents to be treated, allowing more effective chemotherapy. Likewise tissue-type plasminogen activator has been a significant improvement over streptokinase in the therapy of myocardial infarction although, not surprisingly, it is just as difficult to use successfully in stroke as streptokinase. Plasminogen activators have now been tinkered with to improve their performance in the same way as classical medicinal products for treatments in the conventional pharmaceutical arena. The next step in recombinant protein therapeutics is to construct hybrid therapeutic functions. This concept has not been a great success in medicinal chemistry with α/β−adrenoceptor blockers but hope springs eternal and the chapter on immunocytokines makes an interesting read. There is also a chapter on improving protein pharmacokinetics, a universal problem. Finally to generation 3, gene therapy. Here the review by Friedman exhorts us that ‘definitive control of human disease is now in our grasp – loosely but without too much doubt.’ A ringing endorsement? So have the last 20 years seen recombinant technology revolutionize therapeutics? There have been big successes, both medical and financial. Standing back from the hype it seems, nonetheless, that a rather slight collection of therapies have, as yet, been brought forth. Certainly all the recombinant proteins combined would not equal the therapeutic worth of vaccines or antibiotics. The more major contribution of recombinant DNA technology to therapeutics must surely be its role in the discovery process for conventional chemical drugs. The chemical plant seems pretty likely to survive a long while yet.