Brain mitochondrial drug delivery: influence of drug physicochemical properties.

ABSTRACT:

Purpose

To determine the influence of drug physicochemical properties on brain mitochondrial delivery of 20 drugs at physiological pH.

Methods

The delivery of 8 cationic drugs (beta-blockers), 6 neutral drugs (corticosteroids), and 6 anionic drugs (non-steroidal anti-inflammatory drugs, NSAIDs) to isolated rat brain mitochondria was determined with and without membrane depolarization. Multiple linear regression was used to determine whether lipophilicity (Log D), charge, polarizability, polar surface area (PSA), and molecular weight influence mitochondrial delivery.

Results

The Log D for beta-blockers, corticosteroids, and NSAIDs was in the range of -1.41 to 1.37, 0.72 to 2.97, and -0.98 to 2, respectively. The % mitochondrial uptake increased exponentially with an in

SUBMITTER: Durazo SA 

PROVIDER: S-EPMC5510476 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature