Comprehensive Evidence of Carrier-Mediated Distribution of Amantadine to the Retina across the Blood–Retinal Barrier in Rats

Amantadine, a drug used for the blockage of NMDA receptors, is well-known to exhibit neuroprotective effects. Accordingly, assessment of amantadine transport at retinal barriers could result in the application of amantadine for retinal diseases such as glaucoma. The objective of this study was to elucidate the retinal distribution of amantadine across the inner and outer blood–retinal barrier (BRB). In vivo blood-to-retina [3H]amantadine transport was investigated by using the rat retinal uptake index method, which was significantly reduced by unlabeled amantadine. This result indicated the involvement of carrier-mediated processes in the retinal distribution of amantadine. In addition, in vitro model cells of the inner and outer BRB (TR-iBRB2 and RPE-J cells) exhibited saturable kinetics (Km in TR-iBRB2 cells, 79.4 µM; Km in RPE-J cells, 90.5 and 9830 µM). The inhibition of [3H]amantadine uptake by cationic drugs/compounds indicated a minor contribution of transport systems that accept cationic drugs (e.g., verapamil), as well as solute carrier (SLC) organic cation transporters. Collectively, these outcomes suggest that carrier-mediated transport systems, which differ from reported transporters and mechanisms, play a crucial role in the retinal distribution of amantadine across the inner/outer BRB.

Effect of Carbon Chain Length, Ionic Strength, and pH on the In Vitro Release Kinetics of Cationic Drugs from Fatty-Acid-Loaded Contact Lenses

This paper explores the use of fatty acids in silicone hydrogel contact lenses for extending the release duration of cationic drugs. Drug release kinetics was dependent on the carbon chain length of the fatty acid loaded in the lens, with 12-, 14- and 18-carbon chain length fatty acids increasing the uptake and the release duration of ketotifen fumarate (KTF) and tetracaine hydrochloride (THCL). Drug release kinetics from oleic acid-loaded lenses was evaluated in phosphate buffer saline (PBS) at different ionic strengths (I = 167, 500, 1665 mM); the release duration of KTF and THCL was decreased with increasing ionic strength of the release medium. Furthermore, the release of KTF and THCL in deionized water did not show a burst and was significantly slower compared to that in PBS. The release kinetics of KTF and THCL was significantly faster when the pH of the release medium was decreased from 7.4 towards 5.5 because of the decrease in the relative amounts of oleate anions in the lens mostly populated at the polymer–pore interfaces. The use of boundary charges at the polymer–pore interfaces of a contact lens to enhance drug partition and extend its release is further confirmed by loading cationic phytosphingosine in contact lenses to attract an anionic drug.

Cationic drugs and COVID-19

Given the sharp spreading of COVID-19 pandemic all around the world, our attention was brought to consider that that many cationic drugs (i.e. those characterized by the presence, at physiological pH value, of one or more cationic groups, both primary, secondary, tertiary and guanidinic aminic groups) could have any effect in impairing SARS-CoV2 entry in the host cell. This could open to new therapeutic chances against COVID-19.

Release of Cationic Drugs from Charcoal

The goal of this research is to improve preparation of charcoal adducts in a manner suitable for cationic drug release, possibly using an eco-friendly procedure. Charcoal, widely commercialized for human ingestion, is oxidized by hydrogen peroxide in mild conditions. Adducts of a cationic drug (lidocaine hydrochloride, a medication used as local anesthetic) with charcoal are prepared after basification of charcoal and characterized mainly by elemental analysis, wide-angle X-ray diffraction, infrared spectroscopy and thermogravimetry. The drug in the prepared adducts is present in amount close to 30% by weight and can be readily released to both neutral and acidic aqueous solutions. Cation release, as studied by UV spectra of aqueous solutions, is faster in acidic solutions and is faster than for adducts with graphite oxide, which can be prepared only in harsh conditions.