Dataset Information

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac.

ABSTRACT: With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), ?-, ?-, ?-, and HP-?-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, ?-, ?-, ?-, and HP-?-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with ?-, ?-, and HP-?-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-?-CD and Diclo-HP-?-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-?-CD and Diclo-HP-?-CD demonstrated fast healing without scar formation.

SUBMITTER: Abdelkader H

PROVIDER: S-EPMC5831967 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac.

Abdelkader Hamdy H Fathalla Zeinab Z Moharram Hossam H Ali Taha F S TFS Pierscionek Barbara B

Oxidative medicine and cellular longevity 20180213

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, β-, γ-, and HP-β-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, β-, γ-, and HP-β- ...[more]

PMID: 29636847

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Project description:: Chemoradiation therapy is the mainstay for treatment of locally advanced, borderline resectable pancreatic cancer. Pharmacologic ascorbate (P-AscH-, i.e., intravenous infusions of ascorbic acid, vitamin C), but not oral ascorbate, produces high plasma concentrations capable of selective cytotoxicity to tumor cells. In doses achievable in humans, P-AscH- decreases the viability and proliferative capacity of pancreatic cancer via a hydrogen peroxide (H2O2)-mediated mechanism. In this study, we demonstrate that P-AscH- radiosensitizes pancreatic cancer cells but inhibits radiation-induced damage to normal cells. Specifically, radiation-induced decreases in clonogenic survival and double-stranded DNA breaks in tumor cells, but not in normal cells, were enhanced by P-AscH-, while radiation-induced intestinal damage, collagen deposition, and oxidative stress were also reduced with P-AscH- in normal tissue. We also report on our first-in-human phase I trial that infused P-AscH- during the radiotherapy "beam on." Specifically, treatment with P-AscH- increased median overall survival compared with our institutional average (21.7 vs. 12.7 months, P = 0.08) and the E4201 trial (21.7 vs. 11.1 months). Progression-free survival in P-AscH--treated subjects was also greater than our institutional average (13.7 vs. 4.6 months, P < 0.05) and the E4201 trial (6.0 months). Results indicated that P-AscH- in combination with gemcitabine and radiotherapy for locally advanced pancreatic adenocarcinoma is safe and well tolerated with suggestions of efficacy. Because of the potential effect size and minimal toxicity, our findings suggest that investigation of P-AscH- efficacy is warranted in a phase II clinical trial. SIGNIFICANCE: These findings demonstrate that pharmacologic ascorbate enhances pancreatic tumor cell radiation cytotoxicity in addition to offering potential protection from radiation damage in normal surrounding tissue, making it an optimal agent for improving treatment of locally advanced pancreatic adenocarcinoma.

Dataset Information

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac.

Publications

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac.

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