Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model.

Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model. Research Abstract Details 

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Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model. Abstract Text:

Uday B Kompella,Sneha Sundaram,Swita Raghava,Edith R Escobar,

PURPOSE: To determine whether topical ocular delivery of <100 nm nanoparticles can be enhanced by coating their exterior with peptide or protein ligands for cell surface receptors. METHODS: A novel ex vivo bovine eye model was validated for its integrity up to 60 min. Using this model, the uptake of 20 nm polystyrene nanoparticles (administered as a single 50 mul drop) before and after surface conjugation with deslorelin, a luteinizing hormone-releasing hormone (LHRH) agonist, or transferrin was determined at 5 and 60 min in individual layers of cornea and aqueous humor. Selected studies were done in the absence of corneal epithelium in the ex vivo model or using excised cornea and conjunctiva. LHRH and transferrin receptor mRNA and protein expression in corneal epithelium and conjunctiva were determined by real-time PCR and western blot, respectively. RESULTS: Corneal histology, ZO-1 immunostain pattern, and mannitol permeability were similar in controls and at the end of the ex vivo study. Corneal epithelial nanoparticle uptake in the absence of surface modification was 1.1-1.6% at 5 min and remained at about this level even at 60 min. Removal of the corneal epithelium resulted in about 22% particle uptake in the corneal stroma at 5 and 60 min compared to about 0.5% in the presence of epithelium, indicating the barrier nature of corneal epithelium. Deslorelin and transferrin conjugation enhanced corneal epithelial uptake of nanoparticles by 3- and 4.5 fold at 5 min and by 4.5- and 3.8 fold at 60 min, respectively. The total corneal uptake in 5 min is approximately 2.4, 9, and 16% with plain, deslorelin-functionalized, and transferrin-functionalized nanoparticles. In all groups, the nanoparticle uptake per unit tissue weight was in the order: corneal epithelium>stroma>endothelium with levels in the aqueous humor being undetectable. In excised cornea and conjunctiva studies, nanoparticle transport and uptake was elevated for both deslorelin and transferrin conjugated nanoparticles. Expression of LHRH and transferrin receptors was observed in corneal epithelium as well as conjunctiva. CONCLUSIONS: The ex vivo bovine eye model is a useful tool in understanding disposition of nanoparticles after topical delivery. The corneal epithelium is a significant barrier for topical nanoparticle delivery to the anterior segment. Surface modification of nanoparticles by conjugating an LHRH agonist or transferrin is a useful approach to provide rapid, efficient delivery of intact nanoparticles into and/or across cornea and conjunctiva.

Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model. Publishing Authors By Initials

UB Kompella,S Sundaram,S Raghava,ER Escobar,

For similar hormones, hormone substitutes, and hormone antagonists: hormones: peptide hormones: hypothalamic hormones: pituitary hormone-releasing hormones: gonadotropin-releasing hormone: triptorelin research abstracts see: hormones, hormone substitutes, and hormone antagonists: hormones: peptide hormones: hypothalamic hormones: pituitary hormone-releasing hormones: gonadotropin-releasing hormone: triptorelin research

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Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model. Journal Published:

PUBLICATION TYPE: Validation Studies

Journal: Molecular vision

VOLUME: 12

Page Numbers: 1185-98

Journal Abbreviation: Mol. Vis.

ISSN: 1090-0535

DAY: 17

MONTH: 10

YEAR: 2006

Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9605351

Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model. Keywords Mesh Terms:

KEYWORDS: Triptorelin

MESH TERMS: analogs & derivatives

Chemical & Substance for Abstract: Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model. Information

Substance Name: deslorelin

Registry Number: 70235-53-9

Grant and Affiliation Information for Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model.

AFFILIATION: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-5840, USA. ukompell@unmc.edu

Country: United States

AGENCY: United States NEI

GRANT: EY013842

ACRONYM: EY

MEDLINETA: Mol Vis

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