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.
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Maximum DA entrapment efficiency was 63%, and DA peak was highest at day 3 in CSF and plasma of rats while maintaining adequate level up to 30 days compared to inherent DA levels.
“The maximum DA entrapment efficiency was 63%, and the DA peak was reported to be highest at day 3 in both the cerebrospinal fluid and plasma of rats while maintaining an adequate level up to 30 days compared to inherent DA levels.117”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [117]
Intracranial implantation of scaffolds embedded with DA-loaded cellulose acetate phthalate NPs resulted in sustained drug delivery.
“Furthermore, intracranial implantation of scaffolds embedded with DA-loaded cellulose acetate phthalate NPs resulted in sustained drug delivery.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [117]
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- Authors
- Pillay, S., Pillay, V., Choonara, Y. E., Naidoo, D., Khan, R. A., du Toit, L. C., Ndesendo, V. M. K., Modi, G., Danckwerts, M. P., & Iyuke, S. E.
- Affiliations
- University of the Witwatersrand (ZA)
- Integral University (IN)
- Corresponding author
- Pillay, Viness
- ORCID
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 382
- Issue
- 1-2
- Pages
- 277-290
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2058735358
- Cited by
- 80
- References
- 27
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 4 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 4 · 2013: 4 · 2012: 5
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- Parkinson's disease, intracranial drug delivery, alginate scaffolds, Box-Behnken design, controlled release, cerebrospinal fluid, nanoparticle characterization, physicochemical properties
- MeSH terms
- Alginates, Animals, Antiparkinson Agents, Biometry, Calorimetry, Differential Scanning, Cellulose, Chemistry, Pharmaceutical, Computer Simulation, Cross-Linking Reagents, Dopamine, Drug Carriers, Drug Compounding, Drug Implants, Frontal Lobe, Hexuronic Acids, Kinetics, Male, Microscopy, Electron, Scanning, Models, Molecular, Molecular Conformation, Particle Size, Solubility, Surface Properties, Technology, Pharmaceutical, Models, Statistical, Computer-Aided Design, Rats, Sprague-Dawley, Spectroscopy, Fourier Transform Infrared, Glucuronic Acid, Microscopy, Electron, Transmission, Rats, Nanoparticles
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