alexa Optimization and Validation of an In Vitro Blood Brain Barrier Permeability Assay Using Artificial Lipid Membrane
ISSN: 0975-0851

Journal of Bioequivalence & Bioavailability
Open Access

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Research Article

Optimization and Validation of an In Vitro Blood Brain Barrier Permeability Assay Using Artificial Lipid Membrane

Devendrasinh D Jhala1*, Shiva Shankaran Chettiar2and Jitendra Kumar Singh3

1Department of Zoology, School of Sciences, Gujarat University, Ahmedabad, Gujarat-380009, India

2Department of Biotechnology, Shree Ramkrishna Institute of Computer Education and Applied Sciences, Veer Narmad South Gujarat University, Surat, Gujarat-395001, India

3Department of Biotechnology and Bioinformatics, School of Life Sciences, Singhania University, Rajasthan-333515, India

*Corresponding Author:
Devendrasinh D Jhala
Department of Zoology, School of Sciences
Gujarat University, Ahmadabad
Gujarat-380009, India
Tel: +91- 079-27683432
Fax: +91-079-26303196
E-mail: [email protected]

Received Date: May 12, 2012; Accepted Date: June 12, 2012; Published Date: June 14, 2012

Citation: Jhala DD, Chettiar SS, Singh JK (2012) Optimization and Validation of an In Vitro Blood Brain Barrier Permeability Assay Using Artificial Lipid Membrane. J Bioequiv Availab S14:009. doi: 10.4172/jbb.S14-009

Copyright: ©2012 Jhala DD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Blood-Brain Barrier (BBB) is one of the key issues in the pharmaceutical industry since the Central Nervous System (CNS) drugs need to penetrate the barrier, while the peripherally acting drugs should be impaired in the passage. Most of the CNS drugs enter the brain by transcellular passive diffusion mechanism due to the presence of zonula occludens and limited transport pathways. In the present study two different in-vitro methods to predict BBB permeability of drugs were compared and evaluated. We focused our attention on the effect of time on the permeability in PAMPA model to maximize the high through put nature by decreasing the incubation time. Moreover, we have compared the permeability of 16 structurally diverse, commercially available drugs assessed in two different PAMPA models: (1) a PAMPA-PBL (Porcine brain lipid) (2) a PAMPA- Phosphatidylcholine lipid. Both the models successfully identify CNS+ (High brain penetration) and CNS - (Low brain penetration) drugs. A comparison of the permeability by plotting P app values from both methods allows forecasting capacity of the assays. The correlation of the P app value of the both assays with the literature reports showed good correlation of r 2 of 0.9487 and 0.930. The robustness of the established models was further evaluated by establishing correlation of in silico generated logBB values and the experimental logBB values (r 2 0.915). Thus, the developed models have the ability to identify the CNS penetration with reduced incubation times, which in turn will shorten the assay time especially when high throughput screening is employed.

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