TY - JOUR
T1 - Intranasal administration of gold nanoparticles designed to target the central nervous system
T2 - Fabrication and comparison between nanospheres and nanoprisms
AU - Gallardo-Toledo, Eduardo
AU - Tapia-Arellano, Andreas
AU - Celis, Freddy
AU - Sinai, Tomer
AU - Campos, Marcelo
AU - Kogan, Marcelo J.
AU - Sintov, Amnon C.
N1 - Funding Information:
This work was supported by ANID, Ministry of Science, Chile [PhD fellowship number 21151400]; project FONDECYT [number 1170929]; and project FONDAP [number 15130011].
Funding Information:
The authors thank Pedro Jara-Guajardo (PhD student, Departamento de Qu?mica Farmacol?gica y Toxicol?gica, Facultad de Ciencias Qu?micas y Farmac?uticas, Universidad de Chile, Chile), Carolina Velasco-Aguirre (PhD), and the staff of Ilze Katz Institute for Nanoscale Science & Technology (Ben-Gurion University of the Negev, Be'er Sheva, Israel) for their technical support. Eyleen Araya (PhD, Departamento de Ciencias Qu?micas, Facultad de Ciencias Exactas, Universidad Andres Bello, Chile) and Fernando Albericio (PhD, University of KwaZulu-Natal, South Africa) for D1 peptide. This work was supported by ANID, Ministry of Science, Chile [PhD fellowship number 21151400]; project FONDECYT [number 1170929]; and project FONDAP [number 15130011].
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/11/30
Y1 - 2020/11/30
N2 - The presence of the blood–brain barrier (BBB) limit gold nanoparticles (GNP) accumulation in central nervous system (CNS) after intravenous (IV) administration. The intranasal (IN) route has been suggested as a good strategy for circumventing the BBB. In this report, we used gold nanoprisms (78 nm) and nanospheres (47 nm), of comparable surface areas (8000 vs 7235 nm2) functionalized with a polyethylene glycol (PEG) and D1 peptide (GNPr-D1 and GNS-D1, respectively) to evaluate their delivery to the CNS after IN administration. Cell viability assay showed that GNPr-D1 and GNS-D1 were not cytotoxic at concentrations ranged between 0.05 and 0.5 nM. IN administration of GNPr-D1 and GNS-D1 demonstrated a significant difference between the two types of GNP, in which the latter reached the CNS in higher levels. Pharmacokinetic study showed that the peak brain level of gold was 0.75 h after IN administration of GNS-D1. After IN and IV administrations of GNS-D1, gold concentrations found in brain were 55 times higher via the IN route compared to IV administration. Data revealed that the IN route is more effective for targeting gold to the brain than IV administration. Finally, no significant difference was observed between the IN and IV routes in the distribution of GNS-D1 in the various brain areas.
AB - The presence of the blood–brain barrier (BBB) limit gold nanoparticles (GNP) accumulation in central nervous system (CNS) after intravenous (IV) administration. The intranasal (IN) route has been suggested as a good strategy for circumventing the BBB. In this report, we used gold nanoprisms (78 nm) and nanospheres (47 nm), of comparable surface areas (8000 vs 7235 nm2) functionalized with a polyethylene glycol (PEG) and D1 peptide (GNPr-D1 and GNS-D1, respectively) to evaluate their delivery to the CNS after IN administration. Cell viability assay showed that GNPr-D1 and GNS-D1 were not cytotoxic at concentrations ranged between 0.05 and 0.5 nM. IN administration of GNPr-D1 and GNS-D1 demonstrated a significant difference between the two types of GNP, in which the latter reached the CNS in higher levels. Pharmacokinetic study showed that the peak brain level of gold was 0.75 h after IN administration of GNS-D1. After IN and IV administrations of GNS-D1, gold concentrations found in brain were 55 times higher via the IN route compared to IV administration. Data revealed that the IN route is more effective for targeting gold to the brain than IV administration. Finally, no significant difference was observed between the IN and IV routes in the distribution of GNS-D1 in the various brain areas.
KW - Central nervous system
KW - Functionalized nanoparticles
KW - Gold nanoparticles
KW - Intranasal administration
KW - Nose-to-brain delivery
UR - http://www.scopus.com/inward/record.url?scp=85092356067&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2020.119957
DO - 10.1016/j.ijpharm.2020.119957
M3 - Article
C2 - 33035606
AN - SCOPUS:85092356067
VL - 590
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 119957
ER -