From Stoner to local moment magnetism in atomically thin Cr2Te3.

The field of two-dimensional (2D) ferromagnetism has been proliferating over the past few years, with ongoing interests in basic science and potential applications in spintronic technology. However, a high-resolution spectroscopic study of the 2D ferromagnet is still lacking due to the small size and air sensitivity of the exfoliated nanoflakes. Here, we report a thickness-dependent ferromagnetism in epitaxially grown Cr2Te3 thin films and investigate the evolution of the underlying electronic structure by synergistic angle-resolved photoemission spectroscopy, scanning tunneling microscopy, x-ray absorption spectroscopy, and first-principle calculations. A conspicuous ferromagnetic transition from Stoner to Heisenberg-type is directly observed in the atomically thin limit, indicating that dimensionality is a powerful tuning knob to manipulate the novel properties of 2D magnetism. Monolayer Cr2Te3 retains robust ferromagnetism, but with a suppressed Curie temperature, due to the drastic drop in the density of states near the Fermi level. Our results establish atomically thin Cr2Te3 as an excellent platform to explore the dual nature of localized and itinerant ferromagnetism in 2D magnets.

Decoupling wing-shape effects of wing-swept angle and aspect ratio on a forward-flying butterfly.

The effect of wing shape on a forward-flying butterfly via decoupled factors of the wing-swept angle and the aspect ratio (AR) was investigated numerically. The wing-shape effect is a major concern in the design of a microaerial vehicle (MAV). In nature, the wing of a butterfly consists of partially overlapping forewing and hindwing; when the forewing sweeps forward or backward relative to the hindwing, the wing-swept angle and the AR of the entire wing simultaneously change. The effects of the wing-swept angle and AR on aerodynamics are coupled. To decouple their effects, we established wing-shape models with varied combinations of the wing-swept angle and AR based on the experimental measurement of two butterfly species (Papilio polytes and Kallima inachus) and developed a numerical simulation for analysis. In each model, the forewing and hindwing overlapped partially, constructing a single wing. Across the models, the wing-swept angle and AR of these single wings varied sequentially. The results show that, through our models, the effects of the wing-swept angle and AR were decoupled; both have distinct flow mechanisms and aerodynamic force trends and are consistent in the two butterfly species. For a fixed AR, a backward-swept wing increases lift and drag because of the enhanced attachment of the leading-edge vortex with increased strength of the wingtip vortex and the spanwise flow. For a fixed wing-swept angle, a small AR wing increases lift and decreases drag because of the large region of low pressure downstream and the wake-capture effect. Coupling these effects, the largest lift-to-drag ratio occurs for a forward-swept wing with the smallest AR. These results indicate that, in a flapping forward flight, sweeping a forewing forward relative to a hindwing is suitable for cruising. The flow mechanisms and decoupled and coupled effects of the wing-swept angle and the AR presented in this paper provide insight into the flight of a butterfly and the design of a MAV.

Cooperative stability renders protein complex formation more robust and controllable.

Protein complexes are the fundamental units of many biological functions. Despite their many advantages, one major adverse impact of protein complexes is accumulations of unassembled subunits that may disrupt other processes or exert cytotoxic effects. Synthesis of excess subunits can be inhibited via negative feedback control or they can be degraded more efficiently than assembled subunits, with this latter being termed cooperative stability. Whereas controlled synthesis of complex subunits has been investigated extensively, how cooperative stability acts in complex formation remains largely unexplored. To fill this knowledge gap, we have built quantitative models of heteromeric complexes with or without cooperative stability and compared their behaviours in the presence of synthesis rate variations. A system displaying cooperative stability is robust against synthesis rate variations as it retains high dimer/monomer ratios across a broad range of parameter configurations. Moreover, cooperative stability can alleviate the constraint of limited supply of a given subunit and makes complex abundance more responsive to unilateral upregulation of another subunit. We also conducted an in silico experiment to comprehensively characterize and compare four types of circuits that incorporate combinations of negative feedback control and cooperative stability in terms of eight systems characteristics pertaining to optimality, robustness and controllability. Intriguingly, though individual circuits prevailed for distinct characteristics, the system with cooperative stability alone achieved the most balanced performance across all characteristics. Our study provides theoretical justification for the contribution of cooperative stability to natural biological systems and represents a guideline for designing synthetic complex formation systems with desirable characteristics.

Knee-ankle joint line angle: a significant contributor to high-degree knee joint line obliquity in medial opening wedge high tibial osteotomy.

BACKGROUND: Medial opening wedge high tibial osteotomy (MOWHTO) changes the knee joint inclination in the coronal plane, which can be compensated by the ankle joint. Once there is a decompensated knee joint obliquity, it can induce excessive shear force on the articular cartilage. This study aimed to investigate the capacity of the compensation by analyzing the correlation of the knee-ankle joint line angle (KAJA) and the knee joint line obliquity (KJLO). PATIENTS AND METHODS: Ninety-six patients undergoing MOWHTO were included. We measured potential predictors including preoperative or postoperative body mass index (BMI), weight-bearing line (WBL) ratio/correction amount, knee-ankle joint line angle(KAJA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibia angle (MPTA), ankle joint line obliquity (AJLO), mechanical hip-knee-ankle angle (mHKA) and joint line convergence angle (JLCA). The correlations of these predictors and postoperative KJLO were determined using Pearson correlation coefficient. The contribution of significant predictors was further analyzed using multiple linear regression. Finally, the cutoff value of the most contributing factor resulting in decompensated KJLO was derived with receiver operating characteristic (ROC) curve analysis. RESULTS: Preoperative AJLO, JLCA, MPTA, mHKA and KJLO and postoperative KAJA and MPTA correlated with postoperative KJLO. After multiple linear regression, only preoperative AJLO and JLCA and postoperative KAJA still showed significant contribution to postoperative KJLO. Postoperative KAJA made the greatest contribution. The cutoff value of postoperative KAJA was at 9.6° after ROC analysis. The incidence rate of high-grade KJLO was 69.6% when postoperative KAJA exceeded 9.6°. CONCLUSIONS: Postoperative KAJA is a significant contributor to high-grade KJLO after MOWHTO. The incidence was increased at angles greater than 9.6°. The results suggest that KAJA should be carefully assessed during preoperative planning or intraoperative evaluation. Postoperative KAJA < 9.6° can lower the rate of early high-degree KJLO.

Unveiling the Mechanisms Ruling the Efficient Hydrogen Evolution Reaction with Mitrofanovite Pt3Te4.

By means of electrocatalytic tests, surface-science techniques and density functional theory, we unveil the physicochemical mechanisms ruling the electrocatalytic activity of recently discovered mitrofanovite (Pt3Te4) mineral. Mitrofanovite represents a very promising electrocatalyst candidate for energy-related applications, with a reduction of costs by 47% compared to pure Pt and superior robustness to CO poisoning. We show that Pt3Te4 is a weak topological metal with the Z2 invariant, exhibiting electrical conductivity (∼4 × 106 S/m) comparable with pure Pt. In hydrogen evolution reaction (HER), the electrode based on bulk Pt3Te4 shows a very small overpotential of 46 mV at 10 mA cm-2 and a Tafel slope of 36-49 mV dec-1 associated with the Volmer-Heyrovsky mechanism. The outstanding ambient stability of Pt3Te4 also provides durability of the electrode and long-term stability of its efficient catalytic performances.

Focal proximal fibular angle: A potential indicator of the tibial mechanical axis in opening-wedge high tibial osteotomy.

BACKGROUND: For opening-wedge high tibial osteotomy, correct alignment is essential for a better prognosis. It is difficult to evaluate the mechanical axis of the lower extremity or tibia using a single fluoroscopic image. This study aimed to discuss the use of focal proximal fibular angle (FPFA), which can be assessed by a single fluoroscopic image, as an intraoperative indicator. METHODS: Eligible for analyses were 111 consecutively treated patients; for the final analyses 96 patients were included. The preoperative and postoperative medial proximal tibial angle (MPTA) and FPFA were measured. The relationship between these two angles, correction amount, weight-bearing line ratio and patient characteristics were analyzed. RESULTS: The preoperative FPFA and MPTA were 96.5 ± 3.8° (mean ± standard deviation, SD) and 84.8 ± 3.0°, while the postoperative FPFA and MPTA were 87.6 ± 4.1° and 94.0 ± 3.5°, respectively. The preoperative and postoperative sums of the MPTA and FPFA were constant. The discrepancy was less than 3° in all knees, less than 2° in 92.7% knees and less than 1° in 68.8% knees. It was not correlated with age, sex, weight-bearing line ratio, or correction amount. CONCLUSION: The study findings confirmed the constancy of the sum of the MPTA and FPFA. The FPFA can be easily evaluated on a single fluoroscopic image of the knee. Use of the FPFA as guidance may simplify the procedure of opening-wedge high tibial osteotomy and approximately predict the tibial mechanical axis.

Coulombically-stabilized oxygen hole polarons enable fully reversible oxygen redox.

Stabilizing high-valent redox couples and exotic electronic states necessitate an understanding of the stabilization mechanism. In oxides, whether they are being considered for energy storage or computing, highly oxidized oxide-anion species rehybridize to form short covalent bonds and are related to significant local structural distortions. In intercalation oxide electrodes for batteries, while such reorganization partially stabilizes oxygen redox, it also gives rise to substantial hysteresis. In this work, we investigate oxygen redox in layered Na2-XMn3O7, a positive electrode material with ordered Mn vacancies. We prove that coulombic interactions between oxidized oxideanions and the interlayer Na vacancies can disfavor rehybridization and stabilize hole polarons on oxygen (O-) at 4.2 V vs. Na/Na+. These coulombic interactions provide thermodynamic energy saving as large as O-O covalent bonding and enable ~ 40 mV voltage hysteresis over multiple electrochemical cycles with negligible voltage fade. Our results establish a complete picture of redox energetics by highlighting the role of coulombic interactions across several atomic distances and suggest avenues to stabilize highly oxidized oxygen for applications in energy storage and beyond.

Interfacial polymerization of a thin film on contact lenses for improving lubricity.

HYPOTHESIS: A large number of contact lens wearers drop out each year due to end of day discomfort, which could possibly be reduced by designing lenses with highly lubricious surfaces. We hypothesize that polymerizing a thin film of dimethyl acrylamide (DMA) on the surface of the lenses will improve lubricity. EXPERIMENTS: The thin film is polymerized by loading a commercial contact lens (1-DAY ACUVUE® TruEye®) with N,N,N',N'-Tetramethylethane-1,2-diamine (TEMED) and soaking it in a solution of DMA and ammonium per sulfate (APS). The two components of the redox couple (APS and TEMED) mix near the surface of the lens due to diffusion and react rapidly to form free radicals. The free radicals lead the polymerization of the DMA monomer near the surface resulting in the formation of the thin hydrogel layer that is attached to the lens matrix through activation of unreacted vinyl groups or possibly through formation of entanglements with the lens polymer. FINDINGS: The thickness of the layer is controlled by the polymerization time which is limited to 30 s to create a layer of DMA only at the surface. The presence of the DMA layer is confirmed through measurements of Fourier-transform infrared spectroscopy (FTIR) spectra in total internal reflection mode. The layer is determined to be about 3-5 µm thick with a water content of about 285%. The presence of the layer significantly improves lubricity as is evident through the qualitative rubbing test and quantitative measurement of the friction coefficient. A preliminary one-week safety study in rabbits show that lens wear does not cause any toxicity.

The synergy between RSC, Nap1 and adjacent nucleosome in nucleosome remodeling.

Eukaryotes have evolved a specific strategy to package DNA. The nucleosome is a 147-base-pair DNA segment wrapped around histone core proteins that plays important roles regulating DNA-dependent biosynthesis and gene expression. Chromatin remodeling complexes (RSC, Remodel the Structure of Chromatin) hydrolyze ATP to perturb DNA-histone contacts, leading to nucleosome sliding and ejection. Here, we utilized tethered particle motion (TPM) experiments to investigate the mechanism of RSC-mediated nucleosome remodeling in detail. We observed ATP-dependent RSC-mediated DNA looping and nucleosome ejection along individual mononucleosomes and dinucleosomes. We found that nucleosome assembly protein 1 (Nap1) enhanced RSC-mediated nucleosome ejection in a two-step disassembly manner from dinucleosomes but not from mononucleosomes. Based on this work, we provide an entire reaction scheme for the RSC-mediated nucleosome remodeling process that includes DNA looping, nucleosome ejection, the influence of adjacent nucleosomes, and the coordinated action between Nap1 and RSC.

Multidose Preservative Free Eyedrops by Selective Removal of Benzalkonium Chloride from Ocular Formulations.

PURPOSE: About 70% of eye drops contain benzalkonium chloride (BAK) to maintain sterility. BAK is an effective preservative but it can cause irritation and toxicity. We propose to mitigate ocular toxicity without compromising sterility by incorporating a filter into an eye drop bottle to selectively remove BAK during the process of drop instillation. METHODS: The filter is a packed bed of particles made from poly(2-hydroxyethyl methacrylate) (pHEMA), which is a common ophthalmic material. We showed that pHEMA particle prepared by using ethoxylated trimethylolpropane triacrylate as crosslinker can be incorporated into a modified eyedrop bottle tip to selectively remove the preservative as the formulation is squeezed out of the bottle. Hydraulic permeability of the plug is measured to determine the resistance to eye drop squeezing, and % removal of BAK and drugs are determined. RESULTS: The modified tip has a hydraulic permeability of about 2 Darcy, which allows eyedrops formulations to flow through without excessive resistance. The tip is designed such that the patients can create an eyedrop of solution of 1-10 cP viscosity in 4 s with a nominal pressure. During this short contact time, the packed particles removed nearly 100% of benzalkonium chloride (BAK) from a 15 mL, 0.012% BAK solution but have only minimal impact on the concentration of contained active components. CONCLUSION: Our novel design can eliminate the preservative induced toxicity from eye drops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases like glaucoma and dry eyes.

Hybrid Electrospun Polycaprolactone Mats Consisting of Nanofibers and Microbeads for Extended Release of Dexamethasone.

PURPOSE: We designed electrospun polycaprolactone mats consisting of nanofibers and microbeads for extended delivery of dexamethasone. METHODS: Thin flexible dexamethasone loaded polycaprolactone mats were prepared by electrospinning. The solvents, polymer loading, voltage and tip-to-collector distance were varied to explore the effects on microstructure of the mats. The microstructure was determined by scanning electron microscope imaging; drug transport was measured and modeled, and X-ray diffraction was used to gauge the crystallinity. Drug transport and X-ray diffraction studies were also conducted with a spin cast film for comparison. RESULTS: Thin mats, about 10 µm in thickness, were prepared by electrospinning. By controlling the voltage and tip-to-collector distance, we achieved a hybrid structure comprising of nanorods (nanofibers) and microbeads. The release profiles were fitted to the diffusion equation to obtain the diffusivities in the spheres and the rods. The diffusivity in the electrospun nanofibers was significantly lower compared to the casted films due to increased crystallinity, which was estimated from X-ray diffraction analysis. The electrospun hybrid mats sustained drug release for the desired duration of a month, in spite of the small thickness of about 10 µm. By comparison, a ten-fold thicker cast film sustains release for about the same duration suggesting about 100-fold decrease in diffusivity in the electrospun mats due to increased crystallinity. CONCLUSIONS: Electrospun polycaprolactone mats are optimal for achieving long release durations due to increased crystallinity. Designing a hybrid structure by controlling the electrospinning parameters can be a useful approach to increase the release durations.

Mechanistic modeling of ophthalmic drug delivery to the anterior chamber by eye drops and contact lenses.

Ophthalmic drug for the anterior chamber diseases are delivered into tears by either eye drops or by extended release devices placed in the eyes. The instilled drug exits the eye through various routes including tear drainage into the nose through the canaliculi and transport across various ocular membranes. Understanding the mechanisms relevant to each route can be useful in predicting the dependency of ocular bioavailability on various formulation parameters, such as drug concentration, salinity, viscosity, etc. Mathematical modeling has been developed for each of the routes and validated by comparison with experiments. The individual models can be combined into a system model to predict the fraction of the instilled drug that reaches the target. This review summarizes the individual models for the transport of drugs across the cornea and conjunctiva and the canaliculi tear drainage. It also summarizes the combined tear dynamics model that can predict the ocular bioavailability of drugs instilled as eye drops. The predictions from the individual models and the combined model are in good agreement with experimental data. Both experiments and models predict that the corneal bioavailability for drugs delivered through eye drops is less than 5% due to the small area of the cornea in comparison to the conjunctiva, and the rapid clearance of the instilled solution by tear drainage. A contact lens is a natural choice for delivering drugs to the cornea due to the placement of the contact in the immediate vicinity of the cornea. The drug released by the contact towards the cornea surface is trapped in the post lens tear film for extended duration of at least 30min allowing transport of a large portion into the cornea. The model predictions backed by in vivo animal and clinical data show that the bioavailability increases to about 50% with contact lenses. This realization has encouraged considerable research towards delivering ocular drugs by contact lenses. Commercial contacts are, however, not ideal for drug delivery due to the short release durations which may necessitate wearing multiple lenses each day, reducing the viability of this approach. Recent research has focused on designing contacts that retain all critical properties while increasing the release durations to a few hours or a few days. Beagle dog studies with contact lenses containing vitamin E nanobarriers to attenuate drug transport have shown promising results. Human studies using contacts for drug delivery have also been conducted for allergy therapy but drug eluting contacts are not available in the market for any therapy.

Photoprotection and Extended Drug Delivery by UV Blocking Contact Lenses.

PURPOSE: Extended release of photo-unstable drugs from ophthalmic inserts is not useful unless the loaded drug is protected from degradation. Because of the recent interest in extended drug delivery from contact lenses, it is critical to assess whether photo-unstable drugs can be stabilized by loading in lenses. Here, we focus on dexamethasone, which is prone to degradation and has been explored as a candidate for extended release from contact lenses for periods ranging from 10 hours to several days. METHODS: Degradation rates of dexamethasone were measured in phosphate-buffered saline and after loading in contact lenses. The degradation rates were measured in a humidified, constant-temperature (32°C) chamber with controlled UV exposure. Contact lenses with various degrees of UV blocking were used to explore the relationship between degradation rates and UV exposure. It is known that vitamin E absorbs UV radiation; thus, it was loaded into the lenses to explore the feasibility of reducing the degradation rates. RESULTS: About 85% of dexamethasone degraded in 20 hours in non-UV blocking lenses, whereas less than 1% degraded in class 1 UV blocking lenses. Incorporation of vitamin E into the non-UV blocking lenses reduced the fractional degradation to 30%. Degradation rates in phosphate-buffered saline were significantly higher than even in non-UV blocking contact lenses. CONCLUSIONS: The degradation of dexamethasone can be minimized by using a UV blocking contact lens or incorporating vitamin E into a non-UV blocking lens. Vitamin E incorporation has the dual benefits of improving drug stability and release profiles.

Composition, in vitro Anti-inflammatory, Antioxidant and Antimicrobial Activities of the Leaf Essential Oil of Machilus konishii from Taiwan.

The chemical composition and in vitro anti-inflammatory, antioxidant and antimicrobial activities of the leaf essential oil of Machils konishii has been investigated. The essential oil was isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS. Sixty-six compounds were identified, representing 100% of the oil. The main components identified were a-pinene (33.9%), α-pinene (13.9%), and thymol (12.0%); The leaf oil was able to reduce nitric oxide production by lipopolysaccharide-activated murine macrophages RAW 264.7 without reducing the cell viability. In addition, the leaf oil showed strong antioxidant and antimicrobial activities. The major ingredient of the oil that was responsible for the anti-inflammatory, antioxidant and antimicrobial activities was thymol.

Rapid and selective removal of preservative from ophthalmic formulations during eyedrops instillation.

About 70% of eyedrops contain benzalkonium chloride (BAK) as a preservative to prevent the growth of microorganisms. While preservatives are mandated to maintain sterility, many patients exhibit irritation and toxicity to such compounds. We propose to mitigate the ocular toxicity in the ocular formulations without compromising sterility by designing a device that can be incorporated into an eyedrops bottle to selectively remove the preservatives during the process of drop instillation. Here, we specifically focus on macroporous poly(2-hydroxyethyl methacrylate) (pHEMA) gel due to its excellent biocompatibility and high partition coefficient for BAK. In addition to specific selectivity for BAK, the device also requires high hydraulic permeability to allow drop dispensing without excessive pressure drop. The pHEMA monolith can remove nearly 100% of contained BAK from a 25 ml, 0.012% BAK solution with negligible uptake of the hydrophilic drugs such as timolol and dorzolamide. The filter, however, had to be pre-equilibrated with hydrophobic drugs to reach a high separation of BAK without reducing the concentration of the active drug. The average hydraulic permeability of the filter was 0.025 Darcy, which is about 5-fold lower than the ideal value. Incorporation of a pHEMA macroporous gel into an eyedrops bottle can virtually eliminate the exposure of the eyes to the preservatives without compromising the sterility. Our novel design can eliminate the preservative induced toxicity from eyedrops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases such as glaucoma and dry eyes.

Composition, in vitro Anti-inflammatory, Antioxidant and Antimicrobial Activities of Essential Oils from Leaf and Twig Parts of Cupressus cashmeriana.

The chemical composition and in vitro anti-inflammatory, antioxidant and antimicrobial activities of the essential oils isolated from the leaf and twig of Cupressus cashmeriana have been investigated. The essential oils were isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS, respectively. The leaf oil mainly consisted of alpha-pinene (21.8%), epizonarene (8.0%), sabinene (7.9%), limonene (7.6%), gamma-terpinene (7.0%), and allo-aromadendrene (7.0%); the twig oil was mostly carvacrol methyl ether (35.4%), manool (16.1%), carvacrol (14.2%), and (2Z,6E)-farnesol (6.9%). Twig oil, but not leaf oil, was able to reduce nitric oxide production by lipopolysaccharide-activated murine macrophages RAW 264.7 without reducing the cell viability. In addition, twig oil showed better antioxidant and antimicrobial activities than leaf oil. The major ingredient of the twig oil that was responsible for the anti-inflammatory, antioxidant and antimicrobial activities was carvacrol.

Composition, in vitro Cytotoxic, and Antimicrobial Activities of the Flower Essential Oil of Diospyros discolor from Taiwan.

This study investigated the chemical composition, in vitro cytotoxic, and antimicrobial activities of the essential oil isolated from the flower of Diospyros discolor from Taiwan. The essential oil was isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS. Twenty-eight compounds were identified, representing 100% of the oil. The main components identified were (2Z,6E)-farnesol (35.0%), α-cadinol (10.9%), (E)-nerolidol (6.9%), α-humulene (6.0%), τ-cadinol (5.6%), ß-caryophyllene (5.3%), and τ-muurolol (5.3%). The oil exhibited cytotoxic activity against human colon, liver, and lung cancer cells. The active compounds were ß-caryophyllene, α-humulene, τ-cadinol, τ-muurolol, α-cadinol, and (2Z,6E)-farnesol. The antimicrobial activity of the oil was tested by the disc diffusion and micro-broth dilution methods against ten microbial species. The oil exhibited moderate to strong growth suppression against Bacillus cereus, Staphylococcus aureus, S. epidermidis, Escherichia coli, Enterobacter aerogenes, and Candida albicans, with inhibition zones of 40 to 52 mm and MIC values of 31.25-62.5 µg/mL, respectively. For the antimicrobial activities of the oil, the active compounds were determined to be α-cadinol, τ-cadinol, τ-muurolol and (2Z,6E)-farnesol.

Therapeutic contact lenses: a patent review.

INTRODUCTION: Ophthalmic drugs are almost exclusively delivered via eye drops in spite of several deficiencies, including low bioavailability and poor compliance. Contact lenses have the potential to increase bioavailability by an order of magnitude, while also improving compliance. AREAS COVERED: In this review, the authors summarize advances in therapeutic contact lenses. The major focus of the review is on patents on drug-eluting contact lenses, but non-drug-eluting contacts that offer a therapeutic benefit are also included. The content is divided based on the broad technology of the patent, including novel materials, molecular imprinting, diffusion barriers, colloid encapsulation, surface modification, layering, and other novel approaches. In addition to patents, research publications are also included to facilitate the understanding of the mechanisms and challenges. EXPERT OPINION: Among all non-invasive alternatives, contact lenses offer the highest bioavailability to the cornea due to the location of the lens in the immediate vicinity of the cornea. Several approaches have been patented to improve contact lens design for an extended release duration of drugs. Many technologies have successfully integrated suitable drug release profiles into contact lenses, but drug-eluting contacts are not yet commercialized likely due to regulatory challenges, including the high costs of clinical trials.

Dual drug delivery from vitamin E loaded contact lenses for glaucoma therapy.

Glaucoma patients frequently instill eye drops multiple times each day, which is a cause for reduced compliance. Additionally, eye drops suffer from other limitations including low bioavailability, which can lead to side effects. We propose to develop drug-eluting contact lenses for managing glaucoma with increased bioavailability and improved compliance. Contact lenses are developed for extended simultaneous release of timolol and dorzolamide, both of which are commonly prescribed hydrophilic drugs. The extended release is achieved by loading lenses with vitamin E barriers. In vitro release studies are performed with control and vitamin E loaded lenses for both drugs loaded separately and then together in the same lens. The safety and efficacy of combination therapy by contacts are demonstrated in a Beagle model of glaucoma. Simultaneous loading of timolol and dorzolamide increases the release duration of both drugs. Also vitamin E incorporation is highly effective in increasing the release durations of both drugs to about 2-days. The lenses loaded with both drugs exhibited superior IOP reduction compared to eye drops with about 6-fold lower drug loading. More importantly, combination therapy by continuous wear of vitamin E loaded contact for 2-days, followed by a new set of contacts for another two days, reduced IOP during the 4days of wear time and for another 8days after removal of the contacts. Vitamin E loading is very effective for providing combination therapy by contact lenses due to the increase in release durations of several drugs. The contact lens based therapy reduces IOP with lower drug dose compared to eye drops and may significantly improve the compliance as the effect of the therapy lasts significantly longer than the wear-duration.

Composition, in vitro Cytotoxicity, and Anti-mildew Activities of the Leaf Essential Oil of Machilus thunbergii from Taiwan.

This study investigated the chemical composition, in-vitro cytotoxicity, and anti-mildew fungal activities of the essential oil isolated from the leaf of Machilus thunbergii from Taiwan. The essential oil was isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS. Eighty-three compounds were identified, representing 99.8% of the oil. The main components identified were n-decanal (26.6%), ß-caryophyllene (15.8%), α-humulene (10.8%), and ß-eudesmol (10.5%). The oil exhibited cytotoxic activity against human oral, liver, lung, colon, melanoma, and leukemic cancer cells. The active source compounds were ß-caryophyllene, a-humulene, and ß-eudesmol. The anti-mildew activity of the leaf oil was also evaluated. Results showed that the leaf oil had excellent anti-mildew activity. For the anti-mildew activity of the leaf oil, the active source compound was determined to be ß-eudesmol.