title: 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 BaCl(2) imparted crystallinity resulting in significant thermal shifts between native CAP (T(g)=160-170 degrees C; T(m)=192 degrees C) and CAP nanoparticles (T(g)=260 degrees C; T(m)=268 degrees C). DA release displayed an initial lag phase of 24 h and peaked after 3 days, maintaining favorable CSF (10 microg/mL) versus systemic concentrations (1-2 microg/mL) over 30 days and above the inherent baseline concentration of DA (1 microg/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.
authors.affiliation: University of the Witwatersrand, Department of Pharmacy and Pharmacology, 7 York Road, Parktown 2193, Johannesburg, South Africa.
authors.forename: Samantha
authors.initials: S
authors.lastname: Pillay
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Dinesh
authors.initials: D
authors.lastname: Naidoo
authors.forename: Riaz A
authors.initials: RA
authors.lastname: Khan
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.forename: Michael P
authors.initials: MP
authors.lastname: Danckwerts
authors.forename: Sunny E
authors.initials: SE
authors.lastname: Iyuke
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000493:pharmacokinetics*; D001699:Biometry; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D017076:Computer-Aided Design; D003432:Cross-Linking Reagents / Q000737:chemistry; D004298:Dopamine / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D005625:Frontal Lobe / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007700:Kinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000464:Alginates; D000978:Antiparkinson Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D004343:Drug Implants; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D002482:Cellulose; C011708:cellulose acetate phthalate; D004298:Dopamine