Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel

TY - JOUR

T1 - Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel

AU - Wang, Julie Tzu Wen

AU - Rodrigo, Ana C.

AU - Patterson, Anna K.

AU - Hawkins, Kirsten

AU - Aly, Mazen M.S.

AU - Sun, Jia

AU - Al Jamal, Khuloud T.

AU - Smith, David K.

N1 - Funding Information: The authors thank the Centre for Future Health (CFH1b KIT, Wellcome Trust, University of York) for funding this research. JTW led the in vitro and in vivo studies in the laboratory, while the synthetic chemistry, gel characterization and drug release experiments were led by ACR and AKP. Publisher Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7/21

Y1 - 2021/7/21

N2 - This paper reports the use of a self-assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l-DOPA. Based on a two-component combination of an l-glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self-healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l-DOPA. These drug-loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug-loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically-active drugs—a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood–brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with 3H-labeled l-DOPA out-performed a simple intranasal l-DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally-delivered l-DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions.

AB - This paper reports the use of a self-assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l-DOPA. Based on a two-component combination of an l-glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self-healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l-DOPA. These drug-loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug-loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically-active drugs—a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood–brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with 3H-labeled l-DOPA out-performed a simple intranasal l-DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally-delivered l-DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions.

KW - drug delivery

KW - hydrogel

KW - neuroactive drugs, supramolecular gel

UR - http://www.scopus.com/inward/record.url?scp=85106334400&partnerID=8YFLogxK

U2 - 10.1002/advs.202101058

DO - 10.1002/advs.202101058

M3 - Article

AN - SCOPUS:85106334400

SN - 2198-3844

VL - 8

JO - Advanced Science

JF - Advanced Science

IS - 14

M1 - 2101058

ER -