Combination of nanomicellar technology and in situ gelling polymer as ocular drug delivery system (Odds) for cyclosporine-a

A combination of in situ gelling systems and a loaded drug self-assembling nanomicellar carrier was chosen in this study as a new potential Ocular Drug Delivery System (ODDS) for Cy-closporine-A (CyA), a poorly water-soluble drug. Two non-ionic surfactants (d-α-tocopherol polyethylene glycol succinate, VitE-TPGS and polyoxyl 40 hydrogenated castor oil, RH-40) were used to produce the nanomicelles. The physical–chemical characterization of the nanomicelles in terms of CyA entrapment (EE%) and loading efficiency (LE%), cloud point (CP), regeneration time (RT), size and polydispersity index (PI) allowed us to select the best combination of surfactant mixture, which showed appropriate stability, high CyA-EE (99.07%), very small and homogeneous dimen-sions and favored the solubilization of an amount of CyA (0.144% w/w) comparable to that con-tained in marketed emulsion Ikervis®. The selected nanomicellar formulation incorporated into optimized ion-sensitive polymeric dispersions of gellan gum (GG-LA: 0.10, 0.15 and 0.20% w/w) able to trigger the sol–gel transition after instillation was characterized from technological (osmo-lality, pH, gelling capacity, rheological behavior, wettability, TEM and storage stability at 4 and 20 °C) and biopharmaceutical points of view. This new combined approach allowed us to obtain clear aqueous dispersions that were easy to instill and able to form a viscous gel when in contact with the tear fluid, improving CyA ocular bioavailability. Furthermore, this new ODDS prevented CyA transcorneal permeation, exhibited low cytotoxicity and prolonged the CyA resident time in the precorneal area compared to Ikervis®

Hydrogels as Corneal Stroma Substitutes for In Vitro Evaluation of Drug Ocular Permeation

Hydrogels are complex hydrophilic structures, consisting of crosslinked homopolymers or copolymers insoluble in water. Due to their controllable bio-physicochemical properties mimicking the morphology of the native extracellular matrix, they are a key part of a lot of research fields, including medicine, pharmaceutics, and tissue engineering. This paper was focused on the preparation and characterization of hydrogels from different blends of polyvinyl alcohol (PVA) with microcrystalline cellulose (MCC) and gelatin (GEL) at various ratios, and from gelatin and chitosan alone to understand their feasibility of utilizing as corneal stroma substitutes in permeability tests for drug candidate molecules in early stages of their development. The characterization was carried out by differential scanning calorimetry, electron microscopy (SEM), water content, mass loss, water permeability, wettability, and tensile stress-strain tests. After the physicochemical characterization, PVA/MCC blend and chitosan proved to be the most promising constructs, showing negligible mass loss after immersion in aqueous medium for two weeks and low hydrodynamic permeability. They were then employed in drug molecules permeation studies and these data were compared to that obtained through excised tissues. The results obtained showed that PVA/MCC hydrogels have similar mechanical and permeability properties to corneal stroma

Influence of a Combination of Chemical Enhancers and Iontophoresis on In Vitro Transungual Permeation of Nystatin

To promote transungual permeation of nystatin (NYST), molecule with high molecular weight, no water-soluble, amphoteric by iontophoresis. The synergic effect of the combination of cetylpyridinium chloride, CPC, or polyoxyethylene (20) sorbitan monooleate, TW80, and iontophoresis was investigated. In vitro permeation experiments were carried out through bovine hoof slices using vertical diffusion cells. A low current density (0.2 mA/cm2) was applied by introducing Ag/AgCl electrodes in the donor (anode) and receptor (cathode) chambers. The donor phase consisted of a solution, a suspension, or gel-type vehicles containing NYST and surfactants in pH 5.6 HEPES buffer. The addition of CPC to NYST suspension (SOSP) produced a fivefold increase on the permeability of the bovine hoof membrane to the drug. The application of anodal iontophoresis further improved NYST flux. Conversely, NYST transungual permeation was not influenced by TW80 either in the passive diffusion or iontophoretic flux. Furthermore, the iontophoretic treatment does not appear to induce irreversible alterations to the hoof bovine membranes. The present work demonstrated the efficacy of iontophoresis as a treatment for different nail pathologies with large molecules very slightly soluble in water without irreversibly affecting the nail structure. A synergistic effect between CPC and iontophoresis was observed

Assembling surfactants-mucoadhesive polymer nanomicelles (ASMP-nano) for ocular delivery of cyclosporine-A

The physiological protective mechanisms of the eye reduce the bioavailability of topically administered drugs above all for those with high molecular weight and /or lipophilic characteristics, such as Cyclosporine A (CyA). The combined strategy based on the association of nanomicelles and mucoadhesive polymer seems promising since a limited number of commercial products containing CyA have been recently approved. The scope of this investigation was the design of Assembling Surfactants-Mucoadhesive Polymer Nanomicelles (ASMP-Nano), based on a binary system of two surfactants in combination with hyaluronic acid, and their biopharmaceutical evaluation. The optimisation of the ASMP-Nano in term of the amount of surfactants, CyA-loading and size determined the selection of the clear and stable Nano1HAB-CyA formulation containing 0.105% w/w CyA loaded-nanomicelles with a size of 14.41 nm. The nanostructured system had a protective effect towards epithelial corneal cells with a cell viability of more than 80%. It interacted with cellular barriers favouring the uptake and the accumulation of CyA into the cells as evidenced by fluorescent probe distribution, by hindering CyA permeation through reconstituted corneal epithelial tissue. In pharmacokinetics study on rabbits, the nanomicellar carrier prolonged the CyA retention time in the precorneal area mainly in presence of hyaluronic acid (HA), a mucoadhesive polymer

pH-responsive nanostructures based on surface active fatty acid-protic ionic liquids for imiquimod delivery in skin cancer topical therapy

or topical treatment of skin cancer, the design of pH-responsive nanocarriers able to selectively release the drug in the tumor acidic microenvironment represents a reliable option for targeted delivery. In this context, a series of newly synthesized surface-active fatty acid-protic ionic liquids (FA-PILs), based on tetramethylguanidinium cation and different natural hydrophobic fatty acid carboxylates, have been investigated with the aim of developing a pH-sensitive nanostructured drug delivery system for cutaneous administration in the skin cancer therapy. The capability of FA-PILs to arrange in micelles when combined with each other and with the non-ionic surfactant d-α-Tocopherol polyethylene glycol succinate (vitamin E TPGS) as well as their ability to solubilize imiquimod, an immuno-stimulant drug used for the treatment of skin cancerous lesions, have been demonstrated. The FA-PILs-TPGS mixed micelles showed pH-sensitivity, suggesting that the acidic environment of cancer cells can trigger nanostructures’ swelling and collapse with consequent rapid release of imiquimod and drug cytotoxic potential enhancement. The in vitro permeation/penetration study showed that the micellar formulation produced effective imiquimod concentrations into the skin exposed to acid environment, representing a potential efficacious and selective drug delivery system able to trigger the drug release in the tumor tissues, at lower and less irritating drug concentrations. © 2020 by the author

Establishing the tolerability and performance of tamarind seed polysaccharide (TSP) in treating dry eye syndrome: results of a clinical study

BACKGROUND: One of the problems arising from available preparations for dry eye syndrome is the limited residence time of products on the ocular surface. In this paper, we look at an innovative new treatment for dry eye, tamarind seed polysaccharide (TSP). TSP possesses mucomimetic, mucoadhesive and pseudoplastic properties. The 'mucin-like' molecular structure of TSP is similar to corneal and conjunctival mucin 1 (MUC1), a transmembrane glycoprotein thought to play an essential role in protecting and wetting the corneal surface and may explain its increased retention on the eye surface. METHODS: The activity of TSP and hyaluronic acid (HA) in the treatment of dry eye syndrome was compared in an open-label, randomised, single-centre clinical study. Thirty patients were randomised to receive three or more applications per day of either TSP 0.5%, TSP 1% or HA 0.2% (Hyalistil™) over a period of 90 days. The primary objective of tolerability was assessed by visual analogue scale (VAS), scoring of specific symptoms and the incidence of adverse events. Secondary objectives included improvement in stability of the precorneal tear film, subjective symptoms and corneal and conjunctival staining. RESULTS: TSP 0.5% and 1% were comparable to HA 0.2% with regard to both primary and secondary objective parameters. TSP 1% showed benefits over HA 0.2% for the subjective symptoms; trouble blinking, ocular burning and foreign body sensation. CONCLUSION: This study suggests that TSP 0.5% and 1% offer at least equivalent relief to HA 0.2% for dry eye syndrome. All treatments demonstrated optimal tolerability and are suitable for frequent use in the therapy of dry eye. TSP 1% produced promising results in terms of improvements in certain patient symptoms and suggests benefits of the TSP formulation. This study paves the way for a larger study to further establish the performance and safety of TSP compared with HA and highlights the need to expand this therapeutic agent to a wider dry eye population

Sustain-Release of Various Drugs from Leucaena Leucocephala Polysaccharide

This study examines the sustained release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water-insoluble (indomethacin) drugs from Leucaena leucocephala seed Gum isolated from Leucaena leucocephala kernel powder. It further investigates the effect of incorporation of diluents like microcrystalline cellulose and lactose on release of caffeine and partial cross-linking of the gum (polysaccharide) on release of acetaminophen. Applying exponential equation, the mechanism of release of soluble drugs was found to be anomalous. The insoluble drug showed near case II or zero-order release mechanism. The rate of release was in the decreasing order of caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in release kinetics of drug was observed on blending with diluents. However, the rate of release varied with type and amount of blend in the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of release of drug decreased on partial cross-linking and the mechanism of release was found to be super case II

Validation of the italian version of the Cluster Headache Impact Questionnaire (CHIQ)

Background: The Cluster Headache Impact Questionnaire (CHIQ) is a specific and easy-to-use questionnaire to assess the current impact of cluster headache (CH). The aim of this study was to validate the Italian version of the CHIQ. Methods: We included patients diagnosed with episodic CH (eCH) or chronic CH (cCH) according to the ICHD-3 criteria and included in the “Italian Headache Registry” (RICe). The questionnaire was administered to patients through an electronic form in two sessions: at first visit for validation, and after 7 days for test-retest reliability. For internal consistency, Cronbach’s alpha was calculated. Convergent validity of the CHIQ with CH features and the results of questionnaires assessing anxiety, depression, stress, and quality of life was evaluated using Spearman’s correlation coefficient. Results: We included 181 patients subdivided in 96 patients with active eCH, 14 with cCH, and 71 with eCH in remission. The 110 patients with either active eCH or cCH were included in the validation cohort; only 24 patients with CH were characterized by a stable attack frequency after 7 days, and were included in the test-retest cohort. Internal consistency of the CHIQ was good with a Cronbach alpha value of 0.891. The CHIQ score showed a significant positive correlation with anxiety, depression, and stress scores, while showing a significant negative correlation with quality-of-life scale scores. Conclusion: Our data show the validity of the Italian version of the CHIQ, which represents a suitable tool for evaluating the social and psychological impact of CH in clinical practice and research

Usporedba dvaju inhibitora cikooksigenaze u eksperimentalnom modelu suhog oka u albino kunića

The purpose of this study was to compare the topical anti-inflammatory effects of the nonselective cyclooxygenase (COX) inhibitor, ketorolac, with the selective COX-2 inhibitor, nimesulide, in an animal model of dry eye in albino rabbits. All animals were examined by the Schirmer test, tear break-up time (TBUT) and fluorescein corneal staining test. Dry eye model showed significant reduction in tear volume, TBUT, corneal staining and histopathological signs of dryness and inflammation. On treating dry eye model with nimesulide 0.1% eye drops and ketorolac 0.5% eye drops, there were improvements in Schirmer test values, TBUT and fluorescein corneal staining and histopathologically reduced inflammatory reaction, with signs of healing and regeneration. Both nimesulide and ketorolac ameliorate atropine sulphate induced dry eye in albino rabbits. The use of selective COX-2 inhibitor, nimesulide, is preferred to avoid local and systemic side effects which may occur with the use of the nonselective COX inhibitor, ketorolac.Cilj istraživanja bila je usporedba topičkog protuupalnog učinka neselektivnog inhibitora ciklooksigenaze (COX), ketorolaka i selektivnog COX-2 inhibitora, nimesulida na animalnom modelu suhog oka u albino kunića. Na životinjama je proveden Schirmerov test, vrijeme prestanka suzenja oka tear break-up time (TBUT) i test bojenja rožnice fluoresceinom. U animalnom modelu suhog oka značajno je smanjen volumen suza, TBUT, bojenje rožnice i histopatološki simptomi suhoće i upale. Obradom suhog oka s kapima za oči koje sadrže 0,1% nimesulida, odnosno 0,5% ketorolaka, poboljšane su vrijednosti u Schirmerovom testu, TBUT i bojanje rožnice fluoresceinom, smanjena je upalna reakcija, a na oku su se pokazali simptomi ozdravljenja i regeneracije. I nimesulid i ketorolak smanjuju suhoću oka induciranu atropin sulfatom u albino kunića. Uporaba selektivnog COX-2 inhibitora, nimesulida, se preferira jer se izbjegavaju lokalne i sistemske nuspojave koje se mogu pojaviti uz uporabu neselektivnog COX inhibitora, ketorolaka