title: Effect of Cyclodextrins on Morphology and Barrier Characteristics of Isolated Rabbit Corneas.
abstract: The objective of the present study is to investigate the confounding effects, if any, of beta-cyclodextrins (βCDs) on corneal permeability coefficients obtained from in vitro transmembrane diffusion studies. Transcorneal permeability studies were carried out with 2-hydroxypropyl-beta-cyclodextrin (HPβCD) and randomly methylated-beta-cyclodextrin (RMβCD) at 5 and 2.5%w/v in isotonic phosphate-buffered solution (IPBS) (pH 7.4). Rabbit corneas received from Pel-Freez Biologicals® were used for these studies. Propranolol hydrochloride (PHCl) (1 mg/mL) was used as the paracellular permeability marker. A series of permeation studies were carried out with IPBS as the control, with CDs on the donor side only, CDs on the receiver side only, and CDs on both the donor and receiver sides. At the end of 1 or 3 h, corneas were collected and fixed using a solution containing 2%v/v glutaraldehyde + 2%w/v paraformaldehyde + IPBS and histological examinations were performed (Excalibur Pathology, Inc). The order of transcorneal permeability of PHCl was found to be CDs on the receiver side > control (no CDs) ≈ CDs on both the receiver and donor sides > CDs on the donor side. Histology studies revealed that the corneal epithelial and endothelial layers remained intact in the control sets. Damage to the cornea was observed in the order of CDs on the receiver side > CDs on the donor side > CDs on both sides > control. The use of CDs in solutions for in vitro permeation experiments with rabbit corneas needs to be carefully considered to avoid confounding effects in the data obtained.
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA.
authors.forename: Goutham R
authors.initials: GR
authors.lastname: Adelli
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA.
authors.forename: Sai Prachetan
authors.initials: SP
authors.lastname: Balguri
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, 111 Faser Hall, University, Mississippi, 38677, USA. majumso@olemiss.edu.|Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, Mississippi, 38677, USA. majumso@olemiss.edu.
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004058:Diffusion; D066298:In Vitro Techniques; D011433:Propranolol / Q000378:metabolism; D011817:Rabbits; D012995:Solubility; D047392:beta-Cyclodextrins / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011433:Propranolol
keywords: corneal histology; cyclodextrins; in vitro transcorneal permeability; morphology; propranolol hydrochloride