Retinal cell regeneration using tissue engineered polymeric scaffolds

Degenerative retinal diseases, such as age-related macular degeneration (AMD), can lead to permanent sight loss. Although intravitreal anti-vascular endothelial growth factor (VEGF) and steroid injections are effective for the management of early stages of wet and/or neovascular AMD (nAMD), no proven treatments currently exist for dry AMD or for the advanced geographic atrophy of the retina that follows. Tissue engineering (TE) has recently emerged as a promising alternative to repair retinal damaged and restore its functions. Here, we review recent advances in TE, with a particular emphasis on retinal regeneration. We provide an overview of retinal diseases, followed by a comprehensive review of TE techniques, cells, and polymers used in the fabrication of scaffolds for retinal cell regenerations, in particular the retinal pigment epithelium (RPE). - 2019Scopu

Synthesis and Biological Activity of Three Novel Azo Dyes

The azo dyes that named, (E)-4-((2-nitrophenyl) diazenyl) benzene-1,3-diol (1), (E)-4- ((3-nitrophenyl) diazenyl) benzene-1,3-diol (2) and (E)-4-((4-nitrophenyl) diazenyl) benzene-1,3-diol (3) were synthesized and then characterized using IR, UV-visible spectrum. These results were compared with that obtained by ChemBio 3D Ultra - [Chem3D XML] Gaussian Interface and were seems to be identical. Then, the antimicrobial activity of each azo dye was carried out against two bacterial strains: Staphylococcus aureus NCTC 6571, and Escherichia coli ATCC 25922, and fungal strains of Candida albicans using Agar-well diffusion method. The results were showed that the three azo dyes were biologically active and the best reactivity was observed in (2). Though, the biological activity of (1) with NO2 group in ortho- position remained reasonable against Candida albicans. But, the effect of (1) was resisted by Staphylococcus aureus and Escherichia coli. However, the (2) and (3) with substituted NO2 group in meta- and para- positions respectively were showed better reactivity’s than (1) towered Candida albicans and Staphylococcus aureus. Further, the Gaussian interface properties and the conformational analysis of (1), (2) and (3) were intended. The results were indicated that the variations in the properties of each azo dye and their conformational energies of generated conformers can affect their biological activity afterward. Keywords: key words, Azo dyes, Staphylococcus aureus, Escherichia coli, Candida albicans, Agar-well diffusion method, Antimicrobial activit

Electrically atomised formulations of timolol maleate for direct and on-demand ocular lens coatings

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link

Monocaprin eye drop formulation to combat antibiotic resistant gonococcal blindness

Abstract: Neisseria gonorrhoeae bacteria are acknowledged as an urgent threat to human health because this species has developed resistances to all of the antibiotics used clinically to treat its infections. N. gonorrhoeae causes the sexually transmitted disease gonorrhoea, but also causes blindness when the bacteria infect the eyes. Infants are particularly susceptible, acquiring the infection from their mothers at birth. We have shown that the monoglyceride monocaprin rapidly kills N. gonorrhoeae and other bacterial species and is non-irritating in ocular assays. Here we show that the physical and chemical properties of monocaprin make it ideal for use in a thickened eye drop formulation to combat eye infections. Monocaprin-containing formulations were assessed using analytical techniques and for antimicrobial activity in vitro and in ex vivo infections. Monocaprin-containing formulations retained activity after three years and are non-irritating, unlike preparations of povidone iodine in our assays. A recommended formulation for further development and investigation is 0.25% monocaprin in 1% HPMC with 1% polysorbate 20

Studies on surfactants, cosurfactants, and oils for prospective use in formulation of ketorolac tromethamine ophthalmic nanoemulsions

Nanoemulsions (NE) are isotropic, dispersions of oil, water, surfactant(s) and cosurfactant(s). A range of components (11 surfactants, nine cosurfactants, and five oils) were investigated as potential excipients for preparation of ketorolac tromethamine (KT) ocular nanoemulsion. Diol cosurfactants were investigated for the effect of their carbon chain length and dielectric constant (DEC), Log P, and HLB on saturation solubility of KT. Hen’s Egg Test—ChorioAllantoic Membrane (HET-CAM) assay was used to evaluate conjunctival irritation of selected excipients. Of the investigated surfactants, Tween 60 achieved the highest KT solubility (9.89 ± 0.17 mg/mL), followed by Cremophor RH 40 (9.00 ± 0.21 mg/mL); amongst cosurfactants of interest ethylene glycol yielded the highest KT solubility (36.84 ± 0.40 mg/mL), followed by propylene glycol (26.23 ± 0.82 mg/mL). The solubility of KT in cosurfactants was affected by four molecular descriptors: carbon chain length, DEC, log P and HLB. KT solubility was directly proportional to DEC and the HLB yet, inversely proportional to carbon chain length and log P. All surfactants, except Labrasol ALF, were non-irritant. The majority of cosurfactants were slightly irritant, butylene glycol was a moderate irritant, pentylene and hexylene glycols were strong irritants. These findings will inform experiments aimed at developing NE formulations for ocular administration of KT

Incorporating morpholine and oxetane into benzimidazolequinone anti-tumor agents : the discovery of 1,4,6,9-tetramethoxyphenazine from hydrogen peroxide and hydroiodic acid-mediated oxidative cyclizations

The reactivity of hydrogen peroxide and catalytic hydroiodic acid towards 3,6-dimethoxy-2-(cycloamino)anilines is tunable to give ring-fused benzimidazoles or 1,4,6,9-tetramethoxyphenazine in high yield. Mechanisms via a detected nitroso-intermediate are proposed for oxidative cyclization and the unexpected intermolecular displacement of the oxazine. An aqueous solution of molecular iodine is capable of the same transformations. Oxidative demethylation gave targeted benzimidazolequinones, including without cleavage of the incorporated oxetane

Assessing the ex vivo permeation behaviour of functionalised contact lens coatings engineered using an electrohydrodynamic technique

In vitro testing alone is no longer considered sufficient evidence presented solely with respect to drug release and permeation testing. These studies are thought to be more reliable and representative when using tissue or animal models; as opposed to synthetic membranes. The release of anti-glaucoma drug timolol maleate from electrically atomised coatings was assessed here using freshly excised bovine corneal tissue. Electrohydrodynamic processing was utilised to engineer functionalised fibrous polyvinylpyrrolidone-Poly (N-isopropylacrylamide) coatings on the outer side of commercial silicone contact lenses. Benzalkonium chloride, ethylenediaminetetraacetic acid, Brij® 78 and borneol were employed as permeation enhancers to see their effect on ex vivo permeation of timolol maleate through the cornea. Formulations containing permeation enhancers showed a vast improvement with respect to cumulative amount of drug permeating through the cornea as shown by a six fold decrease in lag time compared to enhancer-free formulations. Most drug delivery systems require the drug to pass or permeate through a tissue or biological membrane. This study has shown that to fully appreciate and understand how a novel drug delivery system will behave not only within the device but with the external environment or tissue, it is imperative to have in vitro and ex vivo data in conjunction

Engineering and development of chitosan-based nanocoatings for ocular contact lenses

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.The research manuscript reports on Electrohydrodynamic Atomisation (EHDA) to engineer on-demand novel coatings for ocular contact lenses. A formulation approach was adopted to modulate the release of timolol maleate (TM) using chitosan and borneol. Polymers polyvinylpyrrolidone (PVP) and poly (N-isopropylacrylamide) (PNIPAM) were utilised to encapsulate TM and were electrically atomised to produce optimised, stationary contact lens coatings. The particle and fibre diameter, thermal stability, material compatibility of the formed coatings along with their in vitro release-modulating effect and ocular tolerability were investigated. The results demonstrated highly stable nano-matrices with advantageous morphology and size. All formulations yielded coatings with high TM encapsulation (>88%); with excellent ocular biocompatibility. The coatings presented biphasic and triphasic release profiles; depending on composition. Kinetic modelling revealed a noticeable effect of chitosan; the higher the concentration, the more the release of TM due to chitosan swelling; with the release mechanism changing from Fickian diffusion (1% w/v; n = 0.5) to non-Fickian (5% w/v, 0.45 < n < 0.89). The use of EHDA has not yet been explored in depth within the ocular research remit; engineering on demand lens coatings capable of sustaining TM release. This is likely to offer an alternative dosage form for management of glaucoma with particular emphasis on improving poor patient compliance

Development and characterisation of electrospun timolol maleate-loaded polymeric contact lens coatings containing various permeation enhancers

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Despite exponential growth in research relating to sustained and controlled ocular drug delivery; anatomical and chemical barriers of the eye still pose formulation challenges. Nanotechnology integration into the pharmaceutical industry has aided efforts in potential ocular drug device development. Here, the integration and in vitro effect of four different permeation enhancers (PEs) on the release of anti-glaucoma drug timolol maleate (TM) from polymeric nanofiber formulations is explored. Electrohydrodynamic (EHD) engineering, more specifically electrospinning, was used to engineer nanofibers (NFs) which coated the exterior of contact lenses. Parameters used for engineering included flow rates ranging from 8 to 15 μL/min and a novel EHD deposition system was used; capable of hosting four lenses, masked template and a ground electrode to direct charged atomised structures. SEM analysis of the electrospun structures confirmed the presence of smooth nano-fibers; whilst thermal analysis confirmed the stability of all formulations. In vitro release studies demonstrated a triphasic release; initial burst release with two subsequent sustained release phases with most of the drug being released after 24 hours (86.7%) Biological evaluation studies confirmed the tolerability of all formulations tested with release kinetics modelling results showing drug release was via quasi-Fickian or Fickian diffusion. There were evident differences (p < 0.05) in TM release dependant on permeation enhancer