Resveratrol-Loaded Hydrogel Contact Lenses with Antioxidant and Antibiofilm Performance

Contact lenses (CLs) are prone to biofilm formation, which may cause severe ocular infections. Since the use of antibiotics is associated with resistance concerns, here, two alternative strategies were evaluated to endow CLs with antibiofilm features: copolymerization with the antifouling monomer 2-methacryloyloxyethyl phosphorylcholine (MPC) and loading of the antioxidant resveratrol with known antibacterial activity. MPC has, so far, been used to increase water retention on the CL surface (Proclear® 1 day CLs). Both poly(hydroxyethyl methacrylate) (HEMA) and silicone hydrogels were prepared with MPC covering a wide range of concentrations (from 0 to 101 mM). All hydrogels showed physical properties adequate for CLs and successfully passed the hen’s egg-chorioallantoic membrane (HET-CAM) test. Silicone hydrogels had stronger affinity for resveratrol, with higher loading and a slower release rate. Ex vivo cornea and sclera permeability tests revealed that resveratrol released from the hydrogels readily accumulated in both tissues but did not cross through. The antibiofilm tests against Pseudomonas aeruginosa and Staphylococcus aureus evidenced that, in general, resveratrol decreased biofilm formation, which correlated with its concentration-dependent antibacterial capability. Preferential adsorption of lysozyme, compared to albumin, might also contribute to the antimicrobial activity. In addition, importantly, the loading of resveratrol in the hydrogels preserved the antioxidant activity, even against photodegradation. Overall, the designed hydrogels can host therapeutically relevant amounts of resveratrol to be sustainedly released on the eye, providing antibiofilm and antioxidant performance.

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Micelles of Progesterone for Topical Eye Administration: Interspecies and Intertissues Differences in Ex Vivo Ocular Permeability

Pharmaceutics ◽

10.3390/pharmaceutics12080702 ◽

2020 ◽

Vol 12 (8) ◽

pp. 702 ◽

Cited By ~ 2

Author(s):

Adrián M. Alambiaga-Caravaca ◽

María Aracely Calatayud-Pascual ◽

Vicent Rodilla ◽

Angel Concheiro ◽

Alicia López-Castellano ◽

...

Keyword(s):

Ex Vivo ◽

Chorioallantoic Membrane ◽

Aqueous Solubility ◽

Pluronic F68 ◽

Drug Permeability ◽

Low Viscosity ◽

Hen’S Egg ◽

Ocular Bioavailability ◽

In Situ Gelling

Progesterone (PG) may provide protection to the retina during retinitis pigmentosa, but its topical ocular supply is hampered by PG poor aqueous solubility and low ocular bioavailability. The development of efficient topical ocular forms must face up to two relevant challenges: Protective barriers of the eyes and lack of validated ex vivo tests to predict drug permeability. The aims of this study were: (i) To design micelles using Pluronic F68 and Soluplus copolymers to overcome PG solubility and permeability; and (ii) to compare drug diffusion through the cornea and sclera of three animal species (rabbit, porcine, and bovine) to investigate interspecies differences. Micelles of Pluronic F68 (3–4 nm) and Soluplus (52–59 nm) increased PG solubility by one and two orders of magnitude, respectively and exhibited nearly a 100% encapsulation efficiency. Soluplus systems showed in situ gelling capability in contrast to the low viscosity Pluronic F68 micelles. The formulations successfully passed the hen’s egg-chorioallantoic membrane test (HET-CAM) test. PG penetration through rabbit cornea and sclera was faster than through porcine or bovine cornea, although the differences were also formulation-dependent. Porcine tissues showed intermediate permeability between rabbit and bovine. Soluplus micelles allowed greater PG accumulation in cornea and sclera whereas Pluronic F68 promoted a faster penetration of lower PG doses.

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Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin

Nanomaterials ◽

10.3390/nano9050745 ◽

2019 ◽

Vol 9 (5) ◽

pp. 745 ◽

Cited By ~ 11

Author(s):

Blanca Lorenzo-Veiga ◽

Hakon Hrafn Sigurdsson ◽

Thorsteinn Loftsson ◽

Carmen Alvarez-Lorenzo

Keyword(s):

Mixed Micelles ◽

Water Solubility ◽

Ex Vivo ◽

Chorioallantoic Membrane ◽

Ex Vivo Permeation ◽

Hen’S Egg ◽

Permeation Studies ◽

20 Nm ◽

In Situ Gelling

Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. Soluplus and Pluronic P103 dispersions were prepared in 0.9% NaCl and pH 6.4 buffer, with or without α-cyclodextrin (αCD; 10% w/v), and characterized through particle size, zeta potential, solubilization efficiency, rheological properties, ocular tolerance, in vitro drug diffusion, and ex vivo permeation studies. Soluplus micelles (90–103 nm) and mixed micelles (150–110 nm) were larger than Pluronic P103 ones (16–20 nm), but all showed zeta potentials close to zero. Soluplus, Pluronic P103, and their mixed micelles increased natamycin solubility up to 6.00-fold, 3.27-fold, and 2.77-fold, respectively. Soluplus dispersions and poly(pseudo)rotaxanes exhibited in situ gelling capability, and they transformed into weak gels above 30 °C. All the formulations were non-irritant according to Hen’s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay. Poly(pseudo)rotaxanes facilitated drug accumulation into the cornea and sclera, but led to lower natamycin permeability through the sclera than the corresponding micelles. Poly(pseudo)rotaxanes made from mixed micelles showed intermediate natamycin diffusion coefficients and permeability values between those of Pluronic P103-based and Soluplus-based poly(pseudo)rotaxanes. Therefore, the preparation of mixed micelles may be a useful tool to regulate drug release and enhance ocular permeability.

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Antiangiogenic Activity of Flavonoids: A Systematic Review and Meta-Analysis

Molecules ◽

10.3390/molecules25204712 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4712

Author(s):

Mai Khater ◽

Francesca Greco ◽

Helen M. I. Osborn

Keyword(s):

Systematic Review ◽

Ex Vivo ◽

Meta Analysis ◽

Chorioallantoic Membrane ◽

Structural Features ◽

Antiangiogenic Agents ◽

Antiangiogenic Activity ◽

Wide Range

An imbalance of angiogenesis contributes to many pathologies such as cancer, arthritis and retinopathy, hence molecules that can modulate angiogenesis are of considerable therapeutic importance. Despite many reports on the promising antiangiogenic properties of naturally occurring flavonoids, no flavonoids have progressed to the clinic for this application. This systematic review and meta-analysis therefore evaluates the antiangiogenic activities of a wide range of flavonoids and is presented in two sections. The first part of the study (Systematic overview) included 402 articles identified by searching articles published before May 2020 using ScienceDirect, PubMed and Web of Science databases. From this initial search, different classes of flavonoids with antiangiogenic activities, related pathologies and use of in vitro and/or in/ex vivo angiogenesis assays were identified. In the second part (Meta-analysis), 25 studies concerning the antiangiogenic evaluation of flavonoids using the in vivo chick chorioallantoic membrane (CAM) assay were included, following a targeted search on articles published prior to June 2020. Meta-analysis of 15 out of the 25 eligible studies showed concentration dependent antiangiogenic activity of six compared subclasses of flavonoids with isoflavones, flavonols and flavones being the most active (64 to 80% reduction of blood vessels at 100 µM). Furthermore, the key structural features required for the antiangiogenic activity of flavonoids were derived from the pooled data in a structure activity relationship (SAR) study. All in all, flavonoids are promising candidates for the development of antiangiogenic agents, however further investigations are needed to determine the key structural features responsible for their activity.

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Dual stain kit for the microscopic gram classification of ocular infection bacteria

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100147089 ◽

1993 ◽

Vol 51 ◽

pp. 248-249

Author(s):

Jacob S. Hanker ◽

Dale N. Holdren ◽

Kenneth L. Cohen ◽

Beverly L. Giammara

Keyword(s):

Contact Lenses ◽

Ocular Infection ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Gram Staining ◽

Ocular Infections ◽

Different Types ◽

Culture Positive ◽

Increased Susceptibility

Keratitis and conjunctivitis (infections of the cornea or conjunctiva) are ocular infections caused by various bacteria, fungi, viruses or parasites; bacteria, however, are usually prominent. Systemic conditions such as alcoholism, diabetes, debilitating disease, AIDS and immunosuppressive therapy can lead to increased susceptibility but trauma and contact lens use are very important factors. Gram-negative bacteria are most frequently cultured in these situations and Pseudomonas aeruginosa is most usually isolated from culture-positive ulcers of patients using contact lenses. Smears for staining can be obtained with a special swab or spatula and Gram staining frequently guides choice of a therapeutic rinse prior to the report of the culture results upon which specific antibiotic therapy is based. In some cases staining of the direct smear may be diagnostic in situations where the culture will not grow. In these cases different types of stains occasionally assist in guiding therapy.

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Anti-Biofilm Molecules Targeting Functional Amyloids

Antibiotics ◽

10.3390/antibiotics10070795 ◽

2021 ◽

Vol 10 (7) ◽

pp. 795

Author(s):

Leticia Matilla-Cuenca ◽

Alejandro Toledo-Arana ◽

Jaione Valle

Keyword(s):

Biofilm Formation ◽

Therapeutic Strategy ◽

Research Area ◽

Therapeutic Strategies ◽

Structural Components ◽

Significant Issue ◽

Wide Range ◽

Effective Therapeutic Strategy ◽

Functional Amyloids ◽

Biofilm Matrix

The choice of an effective therapeutic strategy in the treatment of biofilm-related infections is a significant issue. Amyloids, which have been historically related to human diseases, are now considered to be prevailing structural components of the biofilm matrix in a wide range of bacteria. This assumption creates the potential for an exciting research area, in which functional amyloids are considered to be attractive targets for drug development to dissemble biofilm structures. The present review describes the best-characterized bacterial functional amyloids and focuses on anti-biofilm agents that target intrinsic and facultative amyloids. This study provides a better understanding of the different modes of actions of the anti-amyloid molecules to inhibit biofilm formation. This information can be further exploited to improve the therapeutic strategies to combat biofilm-related infections.

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Silver Nanoparticles from Oregano Leaves’ Extracts as Antimicrobial Components for Non-Infected Hydrogel Contact Lenses

International Journal of Molecular Sciences ◽

10.3390/ijms22073539 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3539

Author(s):

Anastasia Meretoudi ◽

Christina N. Banti ◽

Panagiotis K. Raptis ◽

Christina Papachristodoulou ◽

Nikolaos Kourkoumelis ◽

...

Keyword(s):

Silver Nanoparticles ◽

Contact Lenses ◽

Attenuated Total Reflection ◽

Bacterial Strains ◽

Scanning Calorimetry ◽

X Ray ◽

E Coli ◽

Polymer Hydrogels ◽

20 Nm ◽

And Staphylococcus Aureus

The oregano leaves’ extract (ORLE) was used for the formation of silver nanoparticles (AgNPs(ORLE)). ORLE and AgNPs(ORLE) (2 mg/mL) were dispersed in polymer hydrogels to give the pHEMA@ORLE_2 and pHEMA@AgNPs(ORLE)_2 using hydroxyethyl–methacrylate (HEMA). The materials were characterized by X-ray fluorescence (XRF) spectroscopy, X-ray powder diffraction analysis (XRPD), thermogravimetric differential thermal analysis (TG-DTA), derivative thermogravimetry/differential scanning calorimetry (DTG/DSC), ultraviolet (UV-Vis), and attenuated total reflection mode (ATR-FTIR) spectroscopies in solid state and UV–Vis in solution. The crystallite size value, analyzed with XRPD, was determined at 20 nm. The antimicrobial activity of the materials was investigated against Gram-negative bacterial strains Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The Gram-positive ones of the genus of Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus) are known to be involved in microbial keratitis by the means of inhibitory zone (IZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The IZs, which developed upon incubation of P. aeruginosa, E. coli, S. epidermidis, and S. aureus with paper discs soaked in 2 mg/mL of AgNPs(ORLE), were 11.7 ± 0.7, 13.5 ± 1.9, 12.7 ± 1.7, and 14.3 ± 1.7 mm. When the same dose of ORLE was administrated, the IZs were 10.2 ± 0.7, 9.2 ± 0.5, 9.0 ± 0.0, and 9.0 ± 0.0 mm. The percent of bacterial viability when they were incubated over the polymeric hydrogel discs of pHEMA@AgNPs(ORLE)_2 was interestingly low (66.5, 88.3, 77.7, and 59.6%, respectively, against of P. aeruginosa, E. coli, S. epidermidis, and S. aureus) and those of pHEMA@ORLE_2 were 89.3, 88.1, 92.8, and 84.6%, respectively. Consequently, pHEMA@AgNPs(ORLE)_2 could be an efficient candidate toward the development of non-infectious contact lenses.

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A Putative Cro-Like Repressor Contributes to Arylomycin Resistance in Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04597-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3066-3074 ◽

Cited By ~ 9

Author(s):

Arryn Craney ◽

Floyd E. Romesberg

Keyword(s):

Staphylococcus Aureus ◽

Ex Vivo ◽

Transcriptional Regulator ◽

Signal Peptidase ◽

Health Concern ◽

Resistant Bacteria ◽

Type I ◽

Wall Teichoic Acid ◽

Content Type ◽

Wide Range

ABSTRACTAntibiotic-resistant bacteria are a significant public health concern and motivate efforts to develop new classes of antibiotics. One such class of antibiotics is the arylomycins, which target type I signal peptidase (SPase), the enzyme responsible for the release of secreted proteins from their N-terminal leader sequences. Despite the essentiality, conservation, and relative accessibility of SPase, the activity of the arylomycins is limited against some bacteria, including the important human pathogenStaphylococcus aureus. To understand the origins of the limited activity againstS. aureus, we characterized the susceptibility of a panel of strains to two arylomycin derivatives, arylomycin A-C16and its more potent analog arylomycin M131. We observed a wide range of susceptibilities to the two arylomycins and found that resistant strains were sensitized by cotreatment with tunicamycin, which inhibits the first step of wall teichoic acid synthesis. To further understand howS. aureusresponds to the arylomycins, we profiled the transcriptional response ofS. aureusNCTC 8325 to growth-inhibitory concentrations of arylomycin M131 and found that it upregulates the cell wall stress stimulon (CWSS) and an operon consisting of a putative transcriptional regulator and three hypothetical proteins. Interestingly, we found that mutations in the putative transcriptional regulator are correlated with resistance, and selection for resistanceex vivodemonstrated that mutations in this gene are sufficient for resistance. The results begin to elucidate howS. aureuscopes with secretion stress and how it evolves resistance to the inhibition of SPase.

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Fructose Enhanced Reduction of Bacterial Growth on Nanorough Surfaces

MRS Proceedings ◽

10.1557/opl.2013.35 ◽

2013 ◽

Vol 1498 ◽

pp. 73-78 ◽

Cited By ~ 2

Author(s):

N. Gozde Durmus ◽

Erik N. Taylor ◽

Kim M. Kummer ◽

Thomas J. Webster

Keyword(s):

Bacterial Growth ◽

Biofilm Formation ◽

Antibacterial Agents ◽

Bacteria Growth ◽

Planktonic Bacteria ◽

Combined Use ◽

Wide Range ◽

Metabolic Stimulation ◽

Antibacterial Surfaces ◽

First Time

ABSTRACTBiofilms are a major source of medical device-associated infections, due to their persistent growth and antibiotic resistance. Recent studies have shown that engineering surface nanoroughness has great potential to create antibacterial surfaces. In addition, stimulation of bacterial metabolism increases the efficacy of antibacterial agents to eradicate biofilms. In this study, we combined the antibacterial effects of nanorough topographies with metabolic stimulation (i.e., fructose metabolites) to further decrease bacterial growth on polyvinyl chloride (PVC) surfaces, without using antibiotics. We showed for the first time that the presence of fructose on nanorough PVC surfaces decreased planktonic bacteria growth and biofilm formation after 24 hours. Most importantly, a 60% decrease was observed on nanorough PVC surfaces soaked in a 10 mM fructose solution compared to conventional PVC surfaces. In this manner, this study demonstrated that bacteria growth can be significantly decreased through the combined use of fructose and nanorough surfaces and thus should be further studied for a wide range of antibacterial applications.

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Specific Control of Pseudomonas aeruginosa Surface-Associated Behaviors by Two c-di-GMP Diguanylate Cyclases

mBio ◽

10.1128/mbio.00183-10 ◽

2010 ◽

Vol 1 (4) ◽

Cited By ~ 106

Author(s):

Judith H. Merritt ◽

Dae-Gon Ha ◽

Kimberly N. Cowles ◽

Wenyun Lu ◽

Diana K. Morales ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Biofilm Formation ◽

Extracellular Polysaccharide ◽

Diguanylate Cyclase ◽

Flagellar Motility ◽

Critical Question ◽

Cyclic Diguanylate ◽

Critical Signal ◽

Content Type ◽

Wide Range

ABSTRACT The signaling nucleotide cyclic diguanylate (c-di-GMP) regulates the transition between motile and sessile growth in a wide range of bacteria. Understanding how microbes control c-di-GMP metabolism to activate specific pathways is complicated by the apparent multifold redundancy of enzymes that synthesize and degrade this dinucleotide, and several models have been proposed to explain how bacteria coordinate the actions of these many enzymes. Here we report the identification of a diguanylate cyclase (DGC), RoeA, of Pseudomonas aeruginosa that promotes the production of extracellular polysaccharide (EPS) and contributes to biofilm formation, that is, the transition from planktonic to surface-dwelling cells. Our studies reveal that RoeA and the previously described DGC SadC make distinct contributions to biofilm formation, controlling polysaccharide production and flagellar motility, respectively. Measurement of total cellular levels of c-di-GMP in ∆roeA and ∆sadC mutants in two different genetic backgrounds revealed no correlation between levels of c-di-GMP and the observed phenotypic output with regard to swarming motility and EPS production. Our data strongly argue against a model wherein changes in total levels of c-di-GMP can account for the specific surface-related phenotypes of P. aeruginosa. IMPORTANCE A critical question in the study of cyclic diguanylate (c-di-GMP) signaling is how the bacterial cell integrates contributions of multiple c-di-GMP-metabolizing enzymes to mediate its cognate functional outputs. One leading model suggests that the effects of c-di-GMP must, in part, be localized subcellularly. The data presented here show that the phenotypes controlled by two different diguanylate cyclase (DGC) enzymes have discrete outputs despite the same total level of c-di-GMP. These data support and extend the model in which localized c-di-GMP signaling likely contributes to coordination of the action of the multiple proteins involved in the synthesis, degradation, and/or binding of this critical signal.

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Blocking of Bacterial Biofilm Formation by a Fish Protein Coating

Applied and Environmental Microbiology ◽

10.1128/aem.00279-08 ◽

2008 ◽

Vol 74 (11) ◽

pp. 3551-3558 ◽

Cited By ~ 16

Author(s):

Rebecca Munk Vejborg ◽

Per Klemm

Keyword(s):

Biofilm Formation ◽

Fish Muscle ◽

Physicochemical Characteristics ◽

Economic Problem ◽

Bacterial Attachment ◽

Bacterial Biofilm ◽

Adhesive Properties ◽

Muscle Extract ◽

Wide Range ◽

Inert Surfaces

ABSTRACT Bacterial biofilm formation on inert surfaces is a significant health and economic problem in a wide range of environmental, industrial, and medical areas. Bacterial adhesion is generally a prerequisite for this colonization process and, thus, represents an attractive target for the development of biofilm-preventive measures. We have previously found that the preconditioning of several different inert materials with an aqueous fish muscle extract, composed primarily of fish muscle α-tropomyosin, significantly discourages bacterial attachment and adhesion to these surfaces. Here, this proteinaceous coating is characterized with regards to its biofilm-reducing properties by using a range of urinary tract infectious isolates with various pathogenic and adhesive properties. The antiadhesive coating significantly reduced or delayed biofilm formation by all these isolates under every condition examined. The biofilm-reducing activity did, however, vary depending on the substratum physicochemical characteristics and the environmental conditions studied. These data illustrate the importance of protein conditioning layers with respect to bacterial biofilm formation and suggest that antiadhesive proteins may offer an attractive measure for reducing or delaying biofilm-associated infections.

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