Working Paper Communication Version 1 This version is not peer-reviewed

Mixed Self-Assembled Amphiphilic Polymeric Nanoparticles for Intranasal Drug Delivery

Version 1 : Received: 5 August 2020 / Approved: 6 August 2020 / Online: 6 August 2020 (11:22:55 CEST)

How to cite: Schlachet, I.; Moshe Halamish, H.; Sosnik, A. Mixed Self-Assembled Amphiphilic Polymeric Nanoparticles for Intranasal Drug Delivery. Preprints 2020, 2020080161 Schlachet, I.; Moshe Halamish, H.; Sosnik, A. Mixed Self-Assembled Amphiphilic Polymeric Nanoparticles for Intranasal Drug Delivery. Preprints 2020, 2020080161

Abstract

Intranasal (i.n.) administration became an alternative strategy to bypass the blood-brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions and thus, they could be beneficial in the treatment of different medical conditions.

Subject Areas

Central nervous system (CNS); blood-brain barrier (BBB); self-assembled polymeric nanoparticles; intranasal delivery; biodistribution.

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