Why chitosan could be apt candidate for glaucoma drug delivery - An overview.

Most of the people in the world are affected by glaucoma, which leads to irreversible blindness. Several patient friendly treatments are available, nevertheless medications lack an easy and efficient way of sustained delivery. To make the delivery with enhanced bioavailability, biodegradable and non-biodegradable polymers-based drug carriers are explored. However, ocular drug delivery issues have not been resolved yet due to less adhesiveness, poor penetration ability, pH, and temperature dependent burst releases. Chitosan is found to be effective for ocular drug delivery due to excellent physio-chemical properties in terms of overcoming the existing issues. In this review, we aim to highlight why it has been chosen and the holy grail for ocular drug delivery. Besides, we have comprehensively reviewed recent patents on chitosan as a platform for ocular drug delivery and future perspectives on factors, lacunae and challenges that need to be addressed for better ocular delivery methods for glaucoma management.

Moistening the new vaginal misoprostol tablets: does it increase the efficacy of cervical priming before manual vacuum aspiration in first-trimester miscarriage? A randomised clinical trial.

OBJECTIVES: The primary objective of our study was to ascertain whether moistening the Brazilian formulation of vaginal misoprostol tablets increases cervical dilation before manual vacuum aspiration (MVA), compared with use of dry misoprostol, in first-trimester miscarriage. The secondary objective was to ascertain whether there was any correlation between vaginal pH and the degree of cervical dilation using a moistened or dry misoprostol tablet. METHODS: In a single-centre, double-blind, randomised trial, 46 patients with first-trimester miscarriage were randomly allocated to treatment with dry or moistened (with 200 µl distilled water) 2 × 200 µg misoprostol tablets. RESULTS: The median (range) cervical dilation in the wet and dry groups was 8 mm (6-12 mm) and 7 mm (5-10 mm), respectively (p = .06). The median time between misoprostol insertion and carrying out the procedure did not differ between the dry (406 min, range 180-550 min) and wet (448 min, range 180-526 min) groups (p = .1). No correlation was found between vaginal pH and cervical dilation using continuous data (p = .57; r= 0.08; 95% confidence interval -0.02, 0.3) or dichotomous data (pH ≤5/>5; cervical dilation ≥8 mm or <8 mm; p = .8). CONCLUSION: No difference was observed in cervical dilation between moistened and non-moistened misoprostol use prior to MVA.

Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review.

Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects.

PURPOSE: To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. METHODS: Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60 min. The aberration data were analyzed over a 5mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. RESULTS: Hypromellose drops caused an increase in total higher order aberrations (p=<0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p=<0.01, dry eyes p=0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60 min. Differences in comfort levels failed to reach statistical significance. CONCLUSION: Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants.

Comparative study of corneal wetting agents during 25-gauge microincision vitrectomy surgery under a noncontact wide-angle viewing system.

BACKGROUND AND OBJECTIVE: To compare the effects of corneal wetting agents during 25-gauge microincision vitrectomy surgery (MIVS) under a binocular indirect ophthalmic microscope system. MATERIALS AND METHODS: This prospective, randomized, comparative study included 45 eyes undergoing 25-gauge MIVS. The randomly assigned corneal wetting agents were balanced salt solution, ProVisc, and DisCoVisc. The main outcome measures were the frequency of applications, the duration of each application, and the corneal surface status including corneal fluorescein staining score postoperatively. RESULTS: The mean frequency of applications was higher for balanced salt solution (13.6 ± 4.3) than ProVisc (2.7 ± 1.0) or DisCoVisc (1.7 ± 0.5) (P < .001). The duration of each application was longer for DisCoVisc (29.8 ± 6.0 minutes) than balanced salt solution (3.7 ± 1.1 minutes) or ProVisc (17.6 ± 3.6 minutes) (P < .001). The fluorescein staining score was higher for balanced salt solution until 7 days postoperatively (P < .001). CONCLUSION: ProVisc and DisCoVisc could be more effective corneal wetting agents than balanced salt solution by minimizing the frequency of intraoperative application and postoperative corneal injury.

Efficacy of ophthalmic viscosurgical devices in maintaining corneal epithelial hydration and clarity: in vitro assessment.

PURPOSE: To determine the efficacy of hydroxypropyl methylcellulose (HPMC) and hyaluronic acid (HA) in maintaining corneal hydration and optical clarity. SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. DESIGN: Experimental study. METHODS: In porcine autopsy eyes, the effect of 13 ophthalmic viscosurgical devices (OVDs) (5 formulations of HPMC; 8 formulations of HA) in maintaining corneal hydration and optical clarity was tested. The main outcome variables were the time to reach optical clarity of the cornea during dissipation of the OVD and duration of corneal hydration. These variables were assessed after the first application of the OVD, after balanced salt solution application to rehydrate the gel matrix, and after the second application of OVD on top of the first layer. RESULTS: The study used 57 porcine eyes. High-molecular-weight HA 1.5% (zero shear viscosity [ZSV] 55,122 millipascal seconds [mPa.s]) took a significantly shorter time to reach optical clarity than HA 1.4% (ZSV 36,882 mPa.s) (P=.04). Hyaluronic acid 1.4% and HA 1.5% maintained corneal hydration significantly longer than HPMC 2.0% (P<.001). CONCLUSIONS: For corneal hydration during short-lasting surgical procedures such as cataract surgery, the results suggest using HPMC because it distributes quickly and provides an adequate duration of sufficient corneal hydration. For corneal hydration during prolonged surgical procedures, such as vitreoretinal surgery, results suggest using HA 1.5% in the formulation because it provides long-lasting corneal hydration. FINANCIAL DISCLOSURE: Dr. Prinz has a proprietary interest in Croma Pharma GmbH, Leobendorf, Austria. Dr. Findl is a scientific advisor to Croma Pharma GmbH. No other author has a financial or proprietary interest in any material or method mentioned.

XyliMelts time-release adhering discs for night-time oral dryness.

Dry mouth can be caused by medication, CPAP use, radiation treatment and a variety of connective tissue diseases, with the prevalence increasing with age. In most individuals, daytime dryness is easily managed. However, except for a new product tested in this study, there is no product lasting longer than an hour that can be used at night to reduce the perception of oral dryness while sleeping. The purpose of this study was to assess whether a self-adhering, slowly dissolving disc that time-releases 500 mg of xylitol, cellulose gum (lubricant and humectant) and mild mint flavour (XyliMelts for Dry Mouth, OraHealth Corp.) used during sleep would reduce perceived morning oral dryness and discomfort. Fifteen subjects self-identified as having morning oral dryness were evaluated first without treatment and again with the use of XyliMelts for Dry Mouth. Measures of initial morning discomfort and perceived wetness demonstrated significant improvement. Perceived oral wetness scores increased more than threefold with the use of XyliMelts for Dry Mouth while sleeping. These findings suggest that XyliMelts for Dry Mouth may be an effective strategy for managing oral dryness that occurs at night.

Comparison of corneal wetting properties of viscous eye lubricant and balanced salt solution to maintain optical clarity during cataract surgery.

PURPOSE: To compare the corneal wetting properties of balanced salt solution (BSS) and a viscous eye lubricant during cataract surgery. SETTING: Vienna Institute for Research in Ocular Surgery, Department of Ophthalmology, Hanusch Hospital, Vienna, Austria. DESIGN: Prospective randomized controlled study. METHODS: This randomized controlled subject- and examiner-masked study comprised patients scheduled for cataract surgery. The patients were randomly assigned to receive either BSS or hydroxypropyl methylcellulose (HPMC) 2% gel (Cornea_Protect). Fluorescein staining, optical clarity during surgery, application frequency, subjective grading of discomfort, and subjective dryness of the eye were assessed. RESULTS: One hundred one eyes of 97 patients (mean age 73.6 years; range 53 to 87 years) were included in the study. Mean grade of fluorescein staining was 9.46 ± 3.64 (SD) and 9.76 ± 3.27 (SD) in the BSS group and the HPMC 2% group, respectively (P=.67). Median grade of optical clarity during surgery was 2.0 in the BSS group and 1.0 in the HPMC 2% group, a statistically significant difference (P=.03). Median application frequency of BSS was 10 times higher than median application frequency of 1 time for HPMC 2%, a statistically significant difference (P<.001). CONCLUSIONS: Hydroxypropyl methylcellulose 2% provided significantly better optical clarity than BSS during cataract surgery. Because frequent irrigation is not needed and HPMC 2% provides a better view for the surgeon, the use of HPMC 2% results in increased comfort for the patient, especially under topical anaesthesia, and in a simpler and possibly safer surgical procedure. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes.

Use of a mucoadhesive disk for relief of dry mouth: a randomized, double-masked, controlled crossover study.

BACKGROUND: Dry mouth is a frequent complaint of adults worldwide. In those who experience dry mouth, therapeutic options include the use of salivary substitutes and sialogogues. METHODS: The authors compared the efficacy and safety of mucoadhesive disks (OraMoist, Axiomedic, Zurich; distributed by Quantum Health, Eugene, Ore.) applied three times daily with those of placebo mucoadhesive disks in a double-masked, randomized, controlled crossover study. The primary end point of interest was within-participant differences in subjective (visual analog scale) ratings of dry mouth according to the New York University Bluestone Mouthfeel Questionnaire. The secondary end point was within-participant differences in salivary flow rates. RESULTS: Twenty-seven participants completed the single-site study. The results showed no significant difference between the two types of mucoadhesive disks, both of which were associated with a statistically significant improvement in the subjective experience of moistness across the 60-minute period after application and compared with baseline measures after two weeks of use. Furthermore, both disks were associated with a statistically significant improvement in salivary flow rates across the 60-minute period after application and compared with baseline measures after one and two weeks of use. The disks were well tolerated, and participants did not report any adverse events. CONCLUSIONS: The mucoadhesive disks used in this study were safe and provided symptomatic relief from dry mouth. Practice Implications. Patients with dry mouth may benefit from this novel delivery system.

Subjective comparison of 2 daily disposable contact lenses: Focus Dailies with AquaRelease and Proclear 1-Day.

BACKGROUND: Focus Dailies with AquaRelease (CIBA Vision, Duluth, Georgia) is the daily disposable contact lens currently with the highest market share. Proclear 1-Day (CooperVision, Irvine, California) is a new introduction into the daily disposable market. This study compares the subjective preference of these 2 lenses in an independent, head-to-head comparison. METHODS: Forty-one subjects were fit successfully with both brands of daily disposable contact lenses. Subjects wore the lenses for 10 consecutive days. The subjects were surveyed after the 10 days of wear to determine which lens was preferred in terms of comfort, handling, and overall preference. RESULTS: Surveys were collected from 40 subjects. Twenty-four of 40 chose Proclear 1-Day as more comfortable at the end of the day (P = 0.0003). Nineteen of 40 chose Proclear 1-Day as their overall preference (P = 0.0364). CONCLUSION: This study found that Proclear 1-Day was subjectively preferred for end-of-the day comfort and overall preference when compared with the Focus Dailies with AquaRelease or no preference. The authors hope this will give insight to eye care practitioners when deciding which daily disposable contact lens to fit.

The synergistic antimicrobial effect by mechanical agitation and two chlorhexidine preparations on biofilm bacteria.

INTRODUCTION: Irrigation of the root canal with antibacterial solutions is considered an essential part of root canal treatment in endodontics. The purpose of this study was to investigate whether mechanical agitation (ultrasonic or sonic) improves the effectiveness of chlorhexidine against biofilm bacteria in vitro. METHODS: Collagen-coated hydroxyapatite (CHA) disks were exposed to dispersed subgingival plaque for 3 weeks at 37 degrees C. The multispecies biofilms established were subjected for 1 and 3 minutes to CHX-Plus (Vista Dental Products, Racine, WI) and 2% chlorhexidine (CHX), with or without mechanical agitation. After treatment, the amount of dead bacteria in biofilms was analyzed by viability staining and confocal laser scanning microscopy (CLSM). The morphology of biofilms, with or without mechanical agitation, was also examined by CLSM. RESULTS: The structure of the biofilm did not show any obvious change when the solutions surrounding the biofilm were exposed to continuous ultrasonic or sonic agitation. The combined use of mechanical agitation and chlorhexidine had a more pronounced antimicrobial effect against the biofilms than either one alone. Sonic activation (EndoActivator; Advanced Endodontics, Santa Barbara, CA) showed the highest levels of bactericidal activity with CHX-Plus after both exposure times. The proportion of killed bacteria also depended on the type of irrigant (p < 0.001) and the time of exposure (p < 0.001). CONCLUSIONS: The low-intensity ultrasonic or sonic agitation that does not disrupt biofilm or disperse the biofilm bacteria improves the action of disinfectants against biofilm bacteria.

Epinastine 0.05% ophthalmic solution in contact lens-wearing subjects with a history of allergic conjunctivitis.

OBJECTIVES: To assess the comfort and efficacy of epinastine 0.05% ophthalmic solution in contact lens wearers with a history of allergic conjunctivitis and contact lens intolerance during allergy season. METHODS: One hundred forty-six subjects were enrolled in a multicenter, open-label study. Enrolled subjects instilled rewetting drops twice a day for a one-week run-in period, then were randomized to epinastine 0.05% twice a day plus rewetting drops as required (n = 75) or rewetting drops alone as required (minimum use twice a day) (n = 71). Subjects recorded the length of time that contact lens wear was comfortable, the total time of wear, ocular itch, overall comfort, and use of rewetting drops during the run-in period, at baseline, and on days 2 to 7 of the treatment period. RESULTS: Subjects averaged 34 years of age; 79% were female. No significant differences were shown at baseline between subjects treated with epinastine 0.05% twice a day plus rewetting drops and control subjects treated with rewetting drops alone. Averaged over the treatment period, epinastine provided significant increases in comfortable wearing time (1.33 +/- 2.89 vs. 0.43 +/- 2.28 hr, P=0.012) and total wearing time (0.35 +/- 1.87 vs. -0.32 +/- 1.81 hr, P=0.008) compared with controls. Epinastine users reported less frequent additional rewetting drop use on average by 0.56 uses per day, which was significantly different than controls (reduction of 0.06 uses per day; P=0.012). Epinastine provided significantly greater improvements from baseline in ocular itch and overall eye comfort compared with rewetting drops alone (P

Effects of physical and chemical treatments upon biophysical properties and micro-relief of human skin.

The aim of the present study was to determine the attendant effects of physical (tape-stripping) and chemical (three commercial hydrating formulations) treatments upon biophysical and micro-relief properties of human skin. In the first set of experiment, the effects of tape-stripping onto human stratum corneum (SC) biophysical and micro-relief properties were assessed in nine volunteers. Transepidermal water loss (TEWL), skin hydration and micro-relief parameters (including total length of the lines in mm per mm(2); total surface in %; roughness of the skin measured in gray level (Ra); maximum profile valley (Rv) depth; maximum profile peak height (Rp); maximum height (Rt), peak density (Pc) and coefficient of anisotropy) were determined by using SkinEvidence Pro after subsequent tape-stripping of SC. The relevance of roughness determination as gray level by SkinEvidence Pro was confirmed by using surface roughness standards. In the second set of experiment, the effectiveness of three commercial hydrating formulations onto human SC biophysical parameters and micro-relief properties were assessed in six volunteers. TEWL, hydration and micro-relief parameters were assessed onto pre-treated acetone skin and then treated by three commercial hydrating formulations after 2, 4 and 6 h skin exposure. A linear relation between hydration and cutaneous parameters (total length of the lines, Ra and Rp) as function of SC removed was shown. Skin barrier properties evaluated by TEWL measurements, were not modified by topical formulations. However, skin treated by topical formulations showed slightly higher hydration than the one determined in control group, while micro-relief parameters were not modified. In this study was showed that biophysical and micro-relief parameters were closely related in tape-stripping experiment. Efficiency of topical formulations was suggested upon skin hydration but not onto skin micro-relief and barrier function recovering. From both experiments, it appears that different mechanisms relating to skin hydration and potential modification of cutaneous micro-relief were suggested.

Multi-centre evaluation of two daily disposable contact lenses.

PURPOSE: To evaluate the clinical performance of two daily disposable contact lenses: 1-DAY ACUVUE (1DA) (etafilcon A, Johnson & Johnson Vision Care) and FOCUS DAILIES with AquaComfort (FD) (nelfilcon A, CIBA Vision, Inc.), which contains a quickly released moisture enhancing agent, polyvinyl alcohol (PVA). METHODS: This was a 1-week, daily wear, subject-masked, bilateral, parallel group study with subjects randomly assigned to one of two daily disposable soft contact lenses. Subjects were existing soft contact lens wearers in the age range 18-39 years with a spherical refraction between -0.50 and -6.00 D. Subjects were assessed at baseline and after 1 week. Assessments included both subjective (symptoms, wearing time, vision) and objective (lens fit and ocular health) outcomes. RESULTS: Twenty clinical sites enrolled 282 subjects (74% female) of whom 276 (98%) successfully completed the study. Significantly more 1DA wearers reported higher mean comfort scores than with FD (3.95 versus 3.41, respectively, P<0.0001). End-of-day comfort means were also significantly higher with the 1DA group compared to the FD group (3.3 versus 3.0, P=0.03). The 1DA group reported significantly longer mean overall wearing time (1DA was worn on average 0.66+/-0.30 h longer than FD, P=0.03) and longer mean comfortable wearing time (1DA was worn on average 1.73+/-0.35 h longer than FD, P<0.0001). The 1DA lens generally showed significantly better on-eye fitting in terms of movement in primary (P<0.0001) and upgaze (P<0.0001) and ease of removal from the eye (92% versus 63%, P<0.0001) compared to FD. There was significantly less corneal staining observed with the 1DA wearing eyes compared with the FD wearing eyes (23% versus 45%, respectively, P<0.0001). Finally, there was a weak correlation between corneal staining and comfort for FD (r=0.27, P=0.002, n=136), but not for 1DA (r=-0.11, P=0.18, n=140). CONCLUSION: Subjective and objective clinical performance differences between two commonly used daily disposable lenses highlight that, although both lenses may be considered as clinically acceptable, these lenses should not be regarded as interchangeable.

Current contact lens care systems.

Contact lens care has been revolutionized and simplified with the development of multipurpose solutions, less sensitizing preservatives and disinfectants, better protein removers, and reaction-free, one-bottle care systems for patients who have had adverse responses to existing care products. As the complexity of lens care has decreased, compliance has increased. Nevertheless, good compliance is dependent on technician training and a thorough understanding of the chemistry and mechanism of action of each care system. Care products are constantly evolving, and the practitioner should become familiar with each new solution as it is introduced to ensure that patients are also kept up-to-date.

Corneal-wetting property of lignocaine 2% jelly.

PURPOSE: To evaluate the corneal-wetting property of lignocaine 2% jelly. SETTING: A district general hospital. METHODS: Fifty patients having cataract surgery were divided into 3 groups. Group 1 comprised 20 patients who had topical eyedrop anesthesia and corneal irrigation with balanced salt solution (BSS(R)) during surgery as necessary. Group 2 comprised 15 patients who received lignocaine jelly on arrival and just before the corneal incision was made as well as corneal moisturizing by BSS during surgery. Group 3 comprised 15 patients who received lignocaine jelly on arrival and additional lignocaine jelly if necessary just before the corneal incision was made to maintain corneal clarity. The duration of efficacy and the frequency of the applications of the 2 agents were recorded. Corneal clarity and reflections were noted intraoperatively. Corneal status was assessed postoperatively in the ward. RESULTS: Preoperative lignocaine 2% jelly maintained corneal clarity longer than BSS (P <.001). A second application of lignocaine was needed when surgery was prolonged. CONCLUSIONS: The corneal-wetting property of lignocaine 2% jelly can be useful during cataract surgery by avoiding repeated corneal irrigation with BSS.

Effect of surface tension on alveolar surface area.

At fixed lung volume (VL), alterations in surface tension change alveolar surface area (S) and lung recoil (PL). Wilson (26), using data from fixed lungs (1, 9), quantified the isovolume change in S with PL. We reexamined this question in fresh excised rabbit lungs, with two important differences. First, we measured fractional changes in S by using diffuse light scattering, avoiding the potential upset of the balance of tissue and surface forces during fixation. Second, we altered surface tension by ventilating the lungs with nebulized polydimethylsiloxane, with much less residual fluid compared with lavage. We found that S decreased at low and mid VL (treatment surface tension > control) by about half of Wilson's estimates and was nearly unaffected by treatment at high VL. This suggests that with increased surface tension there is 1) greater septal retraction in lungs fixed by vascular perfusion compared with unfixed lungs and 2) a greater increase in PL and less loss of S than would have been predicted.

Lidocaine in ultrasound-assisted lipoplasty.

The doses of lidocaine used for lipoplasty often exceed what is commonly recommended for other surgical procedures. When using these high volumes of lidocaine and wetting solutions, a variety of safety issues must be considered. The author knows of no other plastic surgery operation in which the safety of the procedure is so influenced by the medications administered. Each component of the wetting solution--the alkalized fluid, the epinephrine, and the lidocaine--has an individual and interrelated role. The absorption of lidocaine with epinephrine after subcutaneous installation for lipoplasty probably represents a unique situation, and the concepts presented should not necessarily be extrapolated to other types of procedures.