Effect of Cyclodextrins on Morphology and Barrier Characteristics of Isolated Rabbit Corneas

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 (H...

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Veröffentlicht in:AAPS PharmSciTech 2015-10, Vol.16 (5), p.1220-1226
Hauptverfasser: Adelli, Goutham R., Balguri, Sai Prachetan, Majumdar, Soumyajit
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Balguri, Sai Prachetan
Majumdar, Soumyajit
description 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.
doi_str_mv 10.1208/s12249-015-0315-z
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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 &gt; control (no CDs) ≈ CDs on both the receiver and donor sides &gt; 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 &gt; CDs on the donor side &gt; CDs on both sides &gt; control. 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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 &gt; CDs on the donor side &gt; CDs on both sides &gt; control. 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subjects 2-Hydroxypropyl-beta-cyclodextrin
Animals
beta-Cyclodextrins - pharmacology
beta-Cyclodextrins - toxicity
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cell Membrane Permeability - drug effects
Cornea - drug effects
Cornea - metabolism
Cornea - pathology
Diffusion
In Vitro Techniques
Pharmacology/Toxicology
Pharmacy
Propranolol - metabolism
Rabbits
Rapid Communication
Solubility
title Effect of Cyclodextrins on Morphology and Barrier Characteristics of Isolated Rabbit Corneas
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