Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain

Abstract

This study focused on the design, biometric simulation and optimization of an intracranial nano-enabled scaffold device (NESD) for the site-specific delivery of dopamine (DA) as a strategy to minimize the peripheral side-effects of conventional forms of Parkinson's disease therapy. The NESD was modulated through biometric simulation and computational prototyping to produce a binary crosslinked alginate scaffold embedding stable DA-loaded cellulose acetate phthalate (CAP) nanoparticles optimized in accordance with Box-Behnken statistical designs. The physicomechanical properties of the NESD were characterized and in vitro and in vivo release studies performed. Prototyping predicted a 3D NESD model with enhanced internal micro-architecture. SEM and TEM revealed spherical, uniform and non-aggregated DA-loaded nanoparticles with the presence of CAP (FTIR bands at 1070, 1242 and 2926 cm-1). An optimum nanoparticle size of 197 nm (PdI = 0.03), a zeta potential of -34.00 mV and a DEE of 63% was obtained. The secondary crosslinker BaCl2 imparted crystallinity resulting in significant thermal shifts between native CAP (Tg = 160-170 °C; Tm = 192 °C) and CAP nanoparticles (Tg = 260 °C; Tm = 268 °C). DA release displayed an initial lag phase of 24 h and peaked after 3 days, maintaining favorable CSF (10 μg/mL) versus systemic concentrations (1-2 μg/mL) over 30 days and above the inherent baseline concentration of DA (1 μg/mL) following implantation in the parenchyma of the frontal lobe of the Sprague-Dawley rat model. The strategy of coupling polymeric scaffold science and nanotechnology enhanced the site-specific delivery of DA from the NESD. © 2009 Elsevier B.V. All rights reserved.