Enhancing iPSC-CM Maturation Using a Matrigel-Coated Micropatterned PDMS Substrate.

Cardiac myocytes isolated from adult heart tissue have a rod-like shape with highly organized intracellular structures. Cardiomyocytes derived from human pluripotent stem cells (iPSC-CMs), on the other hand, exhibit disorganized structure and contractile mechanics, reflecting their pronounced immaturity. These characteristics hamper research using iPSC-CMs. The protocol described here enhances iPSC-CM maturity and function by controlling the cellular shape and environment of the cultured cells. Microstructured silicone membranes function as a cell culture substrate that promotes cellular alignment. iPSC-CMs cultured on micropatterned membranes display an in-vivo-like rod-shaped morphology. This physiological cellular morphology along with the soft biocompatible silicone substrate, which has similar stiffness to the native cardiac matrix, promotes maturation of contractile function, calcium handling, and electrophysiology. Incorporating this technique for enhanced iPSC-CM maturation will help bridge the gap between animal models and clinical care, and ultimately improve personalized medicine for cardiovascular diseases. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Cardiomyocyte differentiation of iPSCs Basic Protocol 2: Purification of differentiated iPSC-CMs using MACS negative selection Basic Protocol 3: Micropatterning on PDMS.

Impact of Different Mixing Methods on the Performance of Suspension-Based Transdermal Delivery Systems.

Suspension-based matrix transdermal delivery systems (TDSs) are specialized systems that maintain a continuous driving force for drug delivery over prolonged wear. The pressure-sensitive adhesive (PSA) is the most critical constituent of such systems. Our study aimed to determine the effect of different mixing methods on the performance of silicone PSA-based suspension TDSs. Lidocaine suspension TDSs were prepared using conventional slow rotary mixing, high-speed homogenization, bead-mill homogenization, vortex shaking, and by an unguator. Resultant TDSs were tested for tack, shear, and peel properties and correlated to coat weight, content uniformity, microstructure, and in vitro permeation across dermatomed human skin. Every mixing method tested caused a significant reduction in peel. However, bead-mill homogenization resulted in significant loss of all adhesive properties tested, while unguator-mixed TDSs retained most properties. Good linear correlation (R2 = 1.000) between the shear properties of the TDSs with the average cumulative amount of lidocaine permeated after 24 h was observed, with no significant difference between percutaneous delivery from slow rotary-mixed systems (1334 ± 59.21 µg/cm2) and unguator-mixed systems (1147 ± 108.3 µg/cm2). However, significantly lower delivery from bead-mill homogenized systems (821.1 ± 28.00 µg/cm2) was noted. While many factors affect TDS performance, careful consideration must also be given to the processing parameters during development as they have been shown to affect the resultant system's therapeutic efficacy. Extensive mixing with bead-mill homogenization demonstrated crystallization of drug, loss in adhesive properties, coat weight, and film thickness, with reduced transdermal delivery of lidocaine from the prepared system.

Kinetic Deposition of Polar and Non-polar Lipids on Silicone Hydrogel Contact Lenses.

Purpose: This study investigated kinetic lipid uptake to four silicone hydrogel (SiHy) lenses over a period of four weeks, using an in-vitro radiolabel method. Methods: Four contemporary monthly replacement SiHy lenses (lotrafilcon B, senofilcon C, comfilcon A, samfilcon A) were incubated in three different solutions: 1) An artificial tear solution (ATS) containing 14C-labeled phosphatidylcholine (PC), 2) an ATS containing 14C-cholesteryl oleate (CO) and 3) an ATS containing four 14C-radiolabeled lipids (PC, phosphatidylethanolamine, CO, and cholesterol (total lipid)). After 16 hours, lipids were extracted twice from the lenses with chloroform:methanol and the radioactive counts determined the lipid quantities to simulate 1 day of wear. OPTI-FREE PureMoist (Alcon) was used to clean and disinfect the remaining lenses daily and the lipid quantities were further determined after 2 weeks and 4 weeks. Results: The amount of total lipid increased for all lenses over time (p < .01). After four weeks, total lipid accumulated was 20.26 ± 0.15 µg/lens for senofilcon C, which was significantly higher (p < .01) than all other lens materials (samfilcon A - 17.84 ± 0.21; comfilcon A - 16.65 ± 0.12; lotrafilcon B - 7.41 ± 0.56 µg/lens). CO was highest on lotrafilcon B (1.26 ± 0.13 µg/lens) and senofilcon C attracted the most PC (3.95 ± 0.12 µg/lens) compared to the other materials. Conclusion: The amount of both polar and non-polar lipid deposition on monthly replacement SiHy lenses increased over 4 weeks, with significant differences being seen between lens materials.

Biological acellular pericardial mesh regulated tissue integration and remodeling in a rat model of breast prosthetic implantation.

The use of biological meshes has proven beneficial in surgical restriction and periprosthetic capsular contracture following breast prosthetic-reconstruction. Three different types (smooth, texturized, and polyurethane) of silicone round mini prostheses were implanted under rat skin with or without two different bovine acellular pericardial biological meshes (APMs, BioRipar, and Tutomesh). One hundred eighty-six female rats were divided into 12 groups, sacrificed after 3, 6, and 24 weeks and tissue samples investigated by histology and immunohistochemistry. Implantation of both APMs, with or without prostheses, reduced capsular α-SMA expression and CD3+ inflammatory cell infiltration, increasing capillary density and cell proliferation, with some differences. In particular, Tutomesh was associated with higher peri-APM CD3+ inflammation, prosthetic capsular dermal α-SMA expression and less CD31+ vessels and cell proliferation compared with BioRipar. None differences were observed in tissue integration and remodeling following the APM + prostheses implantation; the different prostheses did not influence tissue remodeling. The aim of our study was to investigate if/how the use of different APMs, with peculiar intrinsic characteristics, may influence tissue integration. The structure of APMs critically influenced tissue remodeling after implantation. Further studies are needed to develop new APMs able to optimize tissue integration and neoangiogenesis minimizing periprosthetic inflammation and fibrosis.

Incisional hernia repair in a high-fidelity silicone model for open retro-muscular mesh implantation with preparation of the fatty triangle: validation and educational impact study.

BACKGROUND: Incisional hernia repair requires detailed anatomic knowledge. Regarding median subxiphoidal hernias, the proper preparation of the fatty triangle is challenging. To foster proficiency-based training, a cost-efficient model for open median retromuscular mesh repair resembling the human body was developed, including the main anatomical structures related to the procedure. The aim is to create and validate a high-fidelity model on open retromuscular mesh repair suitable for "training before doing". MATERIALS AND METHODS: Different types of fabrics for imitation of connective tissue and 2-component silicones were used to construct the incisional hernia model. Sample size for validation of the model was determined by a triangular testing approach. Operations from six beginners and six experts were assessed by three blinded-raters. Reliability and construct-validity were evaluated on a behaviorally anchored rating scale (highest score: 4) for the criteria: "instrument use", "tissue handling", "near misses and errors", and "end-product quality". RESULTS: The model authentically mimicked an open median retromuscular mesh repair. Participants considered the procedure realistic. Reliability was excellent, ranging from 0.811 to 0.974 for "end-product quality", and "tissue handling" respectively. Construct-validity was confirmed with experts significantly outperforming beginners in the "use of instruments" (Mbeg. = 2.33, Mexp. = 3.94, p < 0.001), "tissue handling" (Mbeg. = 2.11, Mexp. = 3.72, p < 0.001), "near misses and errors" (Mbeg. = 2.67, Mexp. = 3.67, p < 0.001), and "end-product quality" (Mbeg. = 2.78, Mexp. = 3.72, p < 0.001). Criterion-validity revealed a paradox effect: beginners performed significantly better than experts (p < 0.05) when preparing the fatty triangle. CONCLUSIONS: The model covers all relevant aspects involved in median-open retromuscular incisional hernia mesh repair. Performance differences between beginners and experts confirm construct-validity and thereby realism of the model. It enables to efficiently improve and practice technical skills of the demanding surgery.

Absorption and Extraction of Inflammatory Mediators From Contact Lens Materials.

OBJECTIVES: This report aimed to explore whether certain inflammatory mediators were absorbed, extracted, or bound by various contact lens materials. METHODS: Comfilcon A, balafilcon A, omafilcon A, and etafilcon A were soaked in 500 and 100 pg/mL of interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), or interleukin-1 receptor antagonist (IL-1Ra), and also in combined solutions of inflammatory mediators (500 pg/mL or 100 pg/mL) separately. Lenses were then extracted in 1:1 2% trifluoroacetic acid:acetonitrile. The extracted and residual concentrations of inflammatory mediators were determined using enzyme-linked immunosorbent assays. Absorbed (control-residual) and firmly bound (absorbed-extracted) concentrations were calculated for analysis. RESULTS: More MMP-9 was absorbed by omafilcon A (466±9 pg/mL) than balafilcon A (P=0.006; 437±11 pg/mL) or etafilcon A (P=0.001; 428±13 pg/mL) when soaked in 500 pg/mL, but no differences in 100 pg/mL. More MMP-9 remained firmly bound to omafilcon A (P=0.03; 174±3 pg/mL), comfilcon A (P=0.049; 168±34 pg/mL), and balafilcon A (P=0.01; 186±14 pg/mL) than etafilcon A (128±22 pg/mL). There were no differences in IL-8 absorption between lenses; however, more IL-8 remained firmly bound to omafilcon A (P=0.01; 336±25 pg/mL) than etafilcon A (106±133 pg/mL) when soaked in 500 pg/mL. No differences were found in concentrations of absorbed or firmly bound IL-1Ra between materials. When the mediators were combined, IL-8 was absorbed more in etafilcon A (P=0.03) than in other lens materials, but the absorbed IL-8 did not remain firmly bound. CONCLUSIONS: The uptake and extraction of inflammatory mediators from contact lenses was affected by competitive binding between the mediators.

In vitro measurement of the permeability of endovascular coils deployed in cerebral aneurysms.

BACKGROUND AND PURPOSE: Aneurysm recurrence is the primary limitation of endovascular coiling treatment for cerebral aneurysms. Coiling is currently quantified by a volumetric porosity measure called packing density (pd). Blood flow through a coil mass depends on the permeability of the coil mass, and not just its pd. The permeability of coil masses has not yet been quantified. Here we measure coil permeability with a traditional falling-head permeameter modified to incorporate idealized aneurysms. METHODS: Silicone replicas of idealized aneurysms were manufactured with three different aneurysm diameters (4, 5, and 8 mm). Four different coil types (Codman Trufill Orbit, Covidien Axium, Microvention Microplex 10, and Penumbra 400) were deployed into the aneurysms with a target pd of 35%. Coiled replicas were installed on a falling-head permeameter setup and the time taken for a column of fluid above the aneurysm to drop a certain height was recorded. Permeability of the samples was calculated based on a simple modification of the traditional permeameter equation to incorporate a spherical aneurysm. RESULTS: The targeted 35% pd was achieved for all samples (35%±1%, P=0.91). Coil permeabilities were significantly different from each other (P<0.001) at constant pd. Microplex 10 coils had the lowest permeability of all coil types. Data suggest a trend of increasing permeability with thicker coil wire diameter (not statistically significant). CONCLUSIONS: A simple in vitro setup was developed to measure the permeabilities of coil masses based on traditional permeametry. Coil permeability should be considered when evaluating the hemodynamic efficacy of coiling instead of just packing density. Coils made of thicker wires may be more permeable, and thus less effective, than coils made from thinner wires. Whether aneurysm recurrence is affected by coil wire diameter or permeability needs to be confirmed with clinical trials.

In vitro permeation and disposition of niacinamide in silicone and porcine skin of skin barrier-mimetic formulations.

Niacinamide (NIA) is an amide form of vitamin B3 which is used in cosmetic formulations to improve various skin conditions and it has also been shown to increase stratum corneum thickness following repeated application. In this study, three doses (5, 20 and 50µL per cm2) of two NIA containing oil-in-water skin barrier-mimetic formulations were evaluated in silicone membrane and porcine ear skin and compared with a commercial control formulation. Permeation studies were conducted over 24h in Franz cells and at the end of the experiment membranes were washed and niacinamide was extracted. For the three doses, retention or deposition of NIA was generally higher in porcine skin compared with silicone membrane, consistent with the hydrophilic nature of the active. Despite the control containing a higher amount of active, comparable amounts of NIA were deposited in skin for all formulations for all doses; total skin absorption values (permeation and retention) of NIA were also comparable across all formulations. For infinite (50µL) and finite (5µL) doses the absolute permeation of NIA from the control formulation was significantly higher in porcine skin compared with both test formulations. This likely reflects differences in formulation components and/or presence of skin penetration enhancers in the formulations. Higher permeation for the 50 and 20µL dose was also evident in porcine skin compared with silicone membrane but the opposite is the case for the finite dose. The findings point to the critical importance of dose and occlusion when evaluating topical formulations in vitro and also the likelihood of exaggerated effects of excipients on permeation at infinite and pseudo-finite dose applications.

Inhibition of mixed fungal and bacterial biofilms on silicone by carboxymethyl chitosan.

Mixed biofilms with fungi and bacteria are the leading cause for the failure of medical silicone devices, such as voice prostheses in laryngectomy. In this study, we determined the effect of carboxymethyl chitosan (CM-chitosan) on mixed biofilm formation of fungi and bacteria on silicone which is widely used for construction of medical devices. Mixed biofilm formations were inhibited 72.87% by CM-chitosan. Furthermore, CM-chitosan significantly decreased the metabolic activity of the biofilms using 2, 3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5 carboxanilide (XTT) reduction assay. The examination using confocal laser scanning microscopy and scanning electron microscope confirmed that CM-chitosan inhibited the mixed biofilm and damaged the cells. Effects of CM-chitosan on different stages of biofilms were also evaluated. CM-chitosan inhibited the adhesion of fungi and bacteria with an efficiency of >90%. It prevented biofilm formation at efficiencies of 69.86%, 50.88% and 46.58% when CM-chitosan was added at 90min, 12h and 24h after biofilm initiation, respectively. Moreover, CM-chitosan inhibited Candida yeast-to-hyphal transition. CM-chitosan was not only able to inhibit the metabolic activity of biofilms, but also active upon the establishment and development of biofilm. Therefore, CM-chitosan may serve as a possible antibiofilm agent to limit biofilm formation on voice prostheses.

Double emulsions based on silicone-fluorocarbon-water and their skin penetration.

Double emulsions have significant potential in pharmacy and cosmetics due to the feasibility of combining incompatible substances in one product and the protection of sensitive compounds by incorporating them into their innermost phase. However, a major drawback of double emulsions is their thermodynamic instability and their strong tendency to coalesce. In the present study, the physicochemical stability, the skin permeation and the skin penetration potential of modified semi-solid double emulsions was investigated. The double emulsions were prepared of the cosmetically applied perfluoropolyethers Fomblin HC/04 or Fomblin HC-OH, silicone, carbomer and water. Measurement of the droplet size and examination of the microscopic images confirmed their physicochemical stability over the observation period of eight weeks. Franz-type diffusion cell experiments revealed no increase in curcumin permeation due to the employed perfluoropolyethers compared to the respective control formulations. The formulations used as control were O/W macroemulsions with or without a Polysorbate 80/Sorbitane monooleate 80 surfactant combination. Likewise, tape stripping studies showed no penetration enhancing effect of the employed perfluoropolyethers which is desirable as both perfluoropolyethers are commonly applied components in human personal-care products.

Kinetics of Competitive Adsorption between Lysozyme and Lactoferrin on Silicone Hydrogel Contact Lenses and the Effect on Lysozyme Activity.

PURPOSE: To determine the effect of competitive adsorption between lysozyme and lactoferrin on silicone hydrogel contact lenses and the effect on lysozyme activity. METHODS: Three commercially available silicone hydrogel contact lens materials (senofilcon A, lotrafilcon B and balafilcon A) were examined, for time points ranging from 10 s to 2 h. Total protein deposition was determined by I(125) radiolabeling of lysozyme and lactoferrin, while the activity of lysozyme was determined by a micrococcal activity assay. RESULTS: Senofilcon A and balafilcon A did not show any relevant competitive adsorption between lysozyme and lactoferrin. Lotrafilcon B showed reduced protein deposition due to competitive adsorption for lactoferrin at all time points and lysozyme after 7.5 min. Co-adsorption of lactoferrin and lysozyme decreased the activity of lysozyme in solution for senofilcon A and lotrafilcon B, but co-adsorption had no effect on the surface activity of lysozyme for all lens types investigated. CONCLUSIONS: Competition between lysozyme and lactoferrin is material specific. Co-adsorption of lysozyme and lactoferrin does not affect the activity of surface-bound lysozyme but can reduce the activity of subsequently desorbed lysozyme.

Flux through silicone and human skin fitted to a series/parallel model.

BACKGROUND: Recent reports of the good correlation between maximum flux through human skin in vitro from water, JMHAQ, and maximum flux through silicone from water, JMPAQ, demand that the mechanism of maximum flux across these two apparently quite different membranes be compared to understand the bases of the correlation. RESULTS/DISCUSSION: A n = 70 log JMPAQ database and a matched n = 55 log JMHAQ database of molecules were found to fit well to a series/parallel model where three parallel solubility dependent pathways existed: a lipid pathway, an aqueous pathway, and a series pathway of alternating lipid and aqueous phases. CONCLUSION: The results of this analysis surprisingly suggest that the architecture of the two membranes present similar solubility based pathways through which drugs diffuse.

Adherence of Candida albicans to silicone is promoted by the human salivary protein SPLUNC2/PSP/BPIFA2.

Interactions between Candida albicans, saliva and saliva-coated oral surfaces are initial events in the colonization of the oral cavity by this commensal yeast, which can cause oral diseases such as candidiasis and denture stomatitis. Candida albicans also colonizes silicone voice prostheses, and the microbial biofilm formed can impair valve function, necessitating frequent prosthesis replacement. We have previously shown that saliva promoted binding of C. albicans cells to silicone in vitro, and that the selective binding of specific salivary proteins to voice prosthesis silicone mediated attachment of C. albicans cells. The C. albicans cells adhered to a polypeptide (or polypeptides) of ~36 kDa eluted from saliva-treated silicone. We show here that a protein of similar size was identified in replicate blots of the eluate from saliva-treated silicone when the blots were probed with antibodies to human SPLUNC2, a salivary protein with reported microbial agglutination properties. In addition, SPLUNC2 was depleted from saliva that had been incubated with silicone coupons. To determine whether SPLUNC2 is a yeast-binding protein, SPLUNC2 cDNA was expressed in Escherichia coli. Purified recombinant His-tagged protein (SPLUNC2r) bound to silicone as demonstrated by immunoblot analysis of an eluate from SPLUNC2r-treated silicone coupons and (35) S-radiolabelled C. albicans cells adhered in a dose-dependent manner to SPLUNC2r-coated silicone. We conclude that SPLUNC2 binds to silicone and acts as a receptor for C. albicans adherence to, and subsequent colonization of, voice prosthesis silicone.

In vitro studies on release and skin permeation of nonivamide from novel oil-in-oil-emulsions.

The purpose of this study was to develop oil-in-oil-emulsions that facilitate long-term treatment for chronic pruritus with capsaicinoids. To this end, oil-in-oil-emulsions, which comprised polydimethyl siloxanes, silicone surfactant and castor oil, were examined. We used nonivamide, a synthetic analogue of capsaicin as the active pharmaceutical ingredient. It was incorporated into castor oil that formed the dispersed phase of the emulsion. We evaluated the influence of formulation variables (nonivamide content, phase volume ratio and viscosity of the silicone oil) on the in vitro release and the permeation of nonivamide. Permeation was found to be controlled by the nonivamide concentration in the dispersed phase and the phase volume ratio. Oil-in-oil-emulsions were found to produce constant permeation rates over a period of 10h. They are thus superior to conventional semisolid formulations as application intervals may be extended.

Effects of the anaerobic respiration of Shewanella oneidensis MR-1 on the stability of extracellular U(VI) nanofibers.

Uranium (VI) is considered to be one of the most widely dispersed and problematic environmental contaminants, due in large part to its high solubility and great mobility in natural aquatic systems. We previously reported that under anaerobic conditions, Shewanella oneidensis MR-1 grown in medium containing uranyl acetate rapidly accumulated long, extracellular, ultrafine U(VI) nanofibers composed of polycrystalline chains of discrete meta-schoepite (UO(3)·2H2O) nanocrystallites. Wild-type MR-1 finally transformed the uranium (VI) nanofibers to uranium (IV) nanoparticles via further reduction. In order to investigate the influence of the respiratory chain in the uranium transformation process, a series of mutant strains lacking a periplasmic cytochrome MtrA, outer membrane (OM) cytochrome MtrC and OmcA, a tetraheme cytochrome CymA anchored to the cytoplasmic membrane, and a trans-OM protein MtrB, were tested in this study. Although all the mutants produced U(VI) nanofibers like the wild type, the transformation rates from U(VI) nanofibers to U(IV) nanoparticles varied; in particular, the mutant with deletion in tetraheme cytochrome CymA stably maintained the uranium (VI) nanofibers, suggesting that the respiratory chain of S. oneidensis MR-1 is probably involved in the stability of extracellular U(VI) nanofibers, which might be easily treated via the physical processes of filtration or flocculation for the remediation of uranium contamination in sediments and aquifers, as well as the recovery of uranium in manufacturing processes.

Highly efficient uptake of ultrafine mesoporous silica nanoparticles with excellent biocompatibility by Liriodendron hybrid suspension cells.

The characteristics of the interactions co-cultures of ultrafine mesoporous silica nanoparticles (MSNs) and the Liriodendron hybrid suspension cells were systematically investigated using laser scanning confocal microscope (LSCM) and scanning electron microscopy (SEM). Using fluorescein isothiocyanate (FITC) labeling, the LSCM observations demonstrated that MSNs (size, 5-15 nm) with attached FITC molecules efficiently penetrated walled plant cells through endocytic pathways, but free FITC could not enter the intact plant cells. The SEM measurements indicated that MSNs readily aggregated on the surface of intact plant cells, and also directly confirmed that MSNs could enter intact plant cells; this was achieved by determining the amount of silicon present. After 24 h of incubation with 1.0 mg mL(-1) of MSNs, the viability of the plant cells was analyzed using fluorescein diacetate staining; the results showed that these cells retained high viability, and no cell death was observed. Interestingly, after the incubation with MSNs, the Liriodendron hybrid suspension cells retained the capability for plant regeneration via somatic embryogenesis. Our results indicate that ultrafine MSNs hold considerable potential as nano-carriers of extracellular molecules, and can be used to investigate in vitro gene-delivery in plant cells.

Tamm-Horsfall protein facilitates catheter associated urinary tract infection.

BACKGROUND: Urinary catheters are associated, commonly with bacteriuria and frequently with urinary tract infection. Tamm-Horsfall Protein (THP) is urine's most abundant protein and is known to bind to uropathogenic bacteria. The role of THP in the pathogenesis of catheter associated urinary tract infection (CAUTI) is not clear. We examined the role of THP in facilitating bacterial binding to urinary catheters in vivo and in vitro. FINDINGS: Twenty one urinary catheters were obtained from 20 hospitalized patients. THP was eluted from the catheter surface and catheter segments were cultured. Additional studies were performed in vitro on unused silicone and latex catheters to determine the binding of THP, and the effect of THP on the binding of Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), to the catheter surface.On catheters obtained from patients, the THP deposition was significantly more on culture positive catheters than on culture negative catheters. In the in vitro studies, THP bound to both silicone and latex catheters, and THP enhanced the adherence of E. coli and P. aeruginosa to both types of catheters. CONCLUSION: THP binds to urinary catheters and facilitates the binding of uropathogenic bacteria to catheters.

Quantification of protein deposits on silicone hydrogel materials using stable-isotopic labeling and multiple reaction monitoring.

This study was designed to use multiple reaction monitoring (MRM) for accurate quantification of contact lens protein deposits. Worn lenses used with a multipurpose disinfecting solution were collected after wear. Individual contact lenses were extracted and then digested with trypsin. MRM in conjunction with stable-isotope-labeled peptide standards was used for protein quantification. The results show that lysozyme was the major protein detected from both lens types. The amount of protein extracted from contact lenses was affected by the lens material. Except for keratin-1 (0.83 ± 0.61 vs 0.77 ± 0.20, p = 0.81) or proline rich protein-4 (0.11 ± 0.04 vs 0.15 ± 0.12, p = 0.97), the amounts of lysozyme, lactoferrin, or lipocalin-1 extracted from balafilcon A lenses (12.9 ± 9.01, 0.84 ± 0.50 or 2.06 ± 1.6, respectively) were significantly higher than that extracted from senofilcon A lenses (0.88 ± 0.13, 0.50 ± 0.10 or 0.27 ± 0.23, respectively) (p < 0.05). The amount of protein extracted from contact lenses was dependent on both the individual wearer and the contact lens material. This may have implications for the development of clinical responses during lens wear for different people and with different types of contact lenses. The use of MRM-MS is a powerful analytical tool for the quantification of specific proteins from single contact lenses after wear.

Transport of a lipophilic ionizable permeant (capric acid) across a lipophilic membrane (silicone polymer membrane) from aqueous buffered solutions in the presence of hydroxypropyl-ß-cyclodextrin.

The present study describes a physical model approach applicable to understanding the transport of highly lipophilic, ionizable drugs across a lipophilic membrane between two aqueous compartments in the presence of a cyclodextrin in the aqueous phase. Model predictions were compared with experimental results of capric acid (HA) transport across a silicone polymer membrane in the presence and in the absence of 2-hydroxypropyl-ß-cyclodextrin (HPB) in the aqueous phase over wide ranges of conditions. Key parameters entering into the physical model calculations were the HA-HPB and the A(-)-HPB binding constants, the unionized and ionized free and the complexed HA species diffusion coefficients, the HA pKa, the HA intrinsic silicone polymer membrane permeability coefficient, and the aqueous boundary layer thickness. All of these key parameters were determined from independent or essentially independent experiments. The agreement between the model predictions and the experiments were generally quite good over the entire ranges of the studied independent variables. The results of this study provide an approach that is useful in the mechanistic understanding of how cyclodextrins may enhance the passive absorption of highly lipophilic, low solubility drug molecules in the intestinal tract.

Reducing pain during the removal of adhesive and adherent products.

Silicone Medical Adhesive Removers (SMARs) have proved a valuable addition to formularies. In the absence of SMARs, trauma following removal of adhesive dressings, ostomy products, retention tapes and monitoring equipment can lead to skin stripping or extension of existing wounds. Those at increased risk of skin stripping include groups such as older people, premature infants and neonates and those with skin fragility syndromes. Appeel® Sterile Sachet (CliniMed) is a sterile SMAR in liquid form supplied in a single-use sachet. The addition of this sterile product to the existing Appeel range of wipes and aerosols provides an adhesive remover suitable for use on broken skin. Unlike delivery from an aerosol, Appeel Sterile Sachet does not feel cold on application, a sensation which can be confused with pain. This article discusses the value of SMARs and in particular the advantages of using the single-use Appeel Sterile Sachet.