Nanoparticle formulations that allow for sustained delivery and brain targeting of the neuropeptide oxytocin

Publication date: 5 September 2018Source: International Journal of Pharmaceutics, Volume 548, Issue 1Author(s): Rokon Uz Zaman, Nihal S. Mulla, Keegan Braz Gomes, Cherilyn D'Souza, Kevin Sean Murnane, Martin J. D'SouzaAbstractOxytocin is a promising candidate for the treatment of social-deficit disorders such as Autism Spectrum Disorder, but oxytocin cannot readily pass the blood-brain barrier. Moreover, oxytocin requires frequent dosing as it is rapidly metabolized in blood. We fabricated four polymeric nanoparticle formulations using poly(lactic-co-glycolic acid) (PLGA) or bovine serum albumin (BSA) as the base material. In order to target them to the brain, we then conjugated the materials to either transferrin or rabies virus glycoprotein (RVG) as targeting ligands. The formulations were characterized in vitro for size, zeta potential, encapsulation efficiency, and release profiles. All formulations showed slightly negative charges and sizes ranging from 100 to 278 nm in diameter, with RVG-conjugated BSA nanoparticles exhibiting the smallest sizes. No formulation was found to be immunogenic or cytotoxic. The encapsulation efficiency was ≥75% for all nanoparticle formulations. Release studies demonstrated that BSA nanoparticle formulation exhibited a faster initial burst of release compared to PLGA particles, in addition to later sustained release. This initial burst release would be favorable for clinical dosing as therapeutic effects could be quickly established, esp...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research