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

详细信息    查看全文

• 作者：Samantha Pillay ; Viness Pillay ; Yahya E. Choonara ; Dinesh Naidoo ; Riaz A. Khan ; Lisa C. du Toit ; Valence M.K. Ndesendo ; Girish Modi ; Michael P. Danckwerts ; Sunny E. Iyuke
• 关键词：Central Nervous System ; Blood– ; brain barrier ; Parkinson's disease ; Dopamine ; Biometric simulation ; Prototyping ; Polymeric scaffold ; Nanoparticles ; Crosslinking ; Controlled drug delivery ; Box– ; Behnken design ; Sprague– ; Dawley rat model
• 刊名：International Journal of Pharmaceutics
• 出版年：2009
• 出版时间：1 December 2009
• 年：2009
• 卷：382
• 期：1-2
• 页码：277-290
• 全文大小：1600 K

文摘

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 (T_g = 160–170 °C; T_m = 192 °C) and CAP nanoparticles (T_g = 260 °C; T_m = 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.