Topical noninvasive retinal drug delivery of a tyrosine kinase inhibitor: 3% cediranib maleate cyclodextrin nanoparticle eye drops in the rabbit eye.

To access publisher's full text version of this article click on the hyperlink belowPurpose: Tyrosine kinase inhibitors inhibit VEGF receptors. If delivered to the retina, they might inhibit oedema and neovascularization such as in age-related macular degeneration and diabetic retinopathy. The aim of this study was to formulate cediranib maleate, a potent VEGF inhibitor, as γ-cyclodextrin nanoparticle eye drops and measure the retinal delivery and overall ocular pharmacokinetics after a single-dose administration in rabbits. Methods: A novel formulation technology with 3% cediranib maleate as γ-cyclodextrin micro-suspension was prepared by autoclaving method. Suitable stabilizers were tested for heat-stable eye drops. The ophthalmic formulation was topically applied to one eye in rabbits. The pharmacokinetics in ocular tissues, tear film and blood samples were studied at 1, 3 and 6 hr after administration. Results: γ-cyclodextrin formed complex with cediranib maleate. The formation of γ-cyclodextrin nanoparticles occurred in concentrated complexing media. Combined stabilizers prevented the degradation of drug during the autoclaving process. Three hours after administration of the eye drops, treated eyes showed cediranib levels of 737 ± 460 nM (mean ± SD) in the retina and 10 ± 6 nM in the vitreous humour. Conclusions: Cediranib maleate in γ-cyclodextrin nanoparticles were stable to heat in presence of stabilizers. The drug as eye drops reached the retina in concentrations that are more than 100 times higher than the 0.4 nM IC50 value reported for the VEGF type-II receptor and thus, presumably, above therapeutic level. These results suggest that γ-cyclodextrin-based cediranib maleate eye drops deliver effective drug concentrations to the retina in rabbits after a single-dose administration. Keywords: cediranib; cyclodextrins; drug delivery; in vivo; neovascularization; pharmacokinetics; topical administration.Oculis ehf, Reykjavik, Icelan

Family members of cancer patients: Needs, quality of life and symptoms of anxiety and depression

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Family members of cancer patient's have multiple needs, many of which are not adequately met. Unmet needs may affect psychological distress and quality of life (QOL). The purpose of this study was to assess needs and unmet needs, QOL, symptoms of anxiety and depression, and the relationship between those variables in a large sample of family members of cancer patients in different phases of illness. MATERIAL AND METHODS: Of 332 family members invited to participate, 330 accepted and 223 (67%) completed a cross-sectional, descriptive study. Data was collected with the Family Inventory of Needs (FIN), Quality of Life Scale (QOLS) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Of 20 needs assessed the mean (SD) number of important needs and unmet needs was 16.4 ± 4.3 and 6.2 ± 5.6, respectively. Twelve important needs were unmet in 40-56% of the sample. The mean number of unmet needs was significantly higher among women than men, other relatives than spouses, younger family members, those currently working and those of patients with metastatic cancer. QOL was similar to what has been reported for healthy populations and cancer caregivers in advanced stages. The prevalence of symptoms of anxiety and depression was high (20-40%). Anxiety scores were higher among women than men and both anxiety and depression scores were highest during years 1-5 compared to the first year and more than five years post diagnosis. There was a positive relationship between number of important needs and QOL, and between needs met and QOL. Additionally, there was a significant relationship between anxiety and unmet needs. Finally, there was a significant relationship between QOL and symptoms of anxiety and depression. CONCLUSION: The results support the importance of screening needs and psychological distress among family members of cancer patients in all phases of illness

Angiotensin Receptor Blockers in cyclodextrin nanoparticle eye drops: Ocular pharmacokinetics and pharmacologic effect on intraocular pressure.

To access publisher's full text version of this article click on the hyperlink belowPurpose: Orally administered angiotensin II receptor blockers (ARBs) decrease intraocular pressure (IOP). Topical administration may reduce systemic side effects and result in a useful glaucoma drug. The aim of this study is to test the ocular delivery and pharmacologic effect of nanoparticle eye drops containing ARBs (e.g. irbesartan and candesartan). Methods: 1.5% irbesartan and 0.15% candesartan eye drops were applied to rabbits. The pharmacokinetics in cornea and aqueous humour after single eye drop application were studied in 49 rabbits. The effect of the eye drops on IOP was studied in 10 rabbits using an iCare (® TonoVet Plus, iCare, Finland) tonometer and compared with 0.5% timolol eye drops. Results: Candesartan lowered IOP from 24.6 ± 5.1 mmHg at baseline to 19.0 ± 2.9 mmHg (mean ± SD, p = 0.030, n = 10) 4 hr after application. Irbesartan lowered IOP from 24.2 ± 1.7 mmHg to 20.2 ± 0.9 mmHg (p = 0.14, n = 10). Timolol decreased the IOP from 24.9 ± 4.2 mmHg to 20.4 ± 4.8 mmHg (mean ± SD, p = 0.036, n = 10). The pharmacokinetics data show that both formulations deliver effective amounts of drug into the intraocular tissues, with irbesartan and candesartan reaching concentrations of 121 ± 69 and 30.43 ± 13.93 ng/g (mean ± SD), respectively, in the aqueous humour 3 hr after a single-dose administration. Conclusions: Topical application of irbesartan and candesartan eye drops delivers effective drug concentrations to the anterior segment of the eye in rabbits, achieving drug concentrations 100 times above the IC50 for angiotensin II receptor and showing an IOP-lowering effect. Angiotensin receptor blocker (ARB) eye drops have potential as a new class of glaucoma drugs. Keywords: angiotensin receptor blockers; glaucoma; intraocular pressure; pharmacokinetics.European Union's programme Eurostar European Union (EU