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

AU - Campo Rodrigo, Ana

AU - Patterson, Anna

AU - Hawkins, Kirsten

AU - Aly, Mazen

AU - Sun, Jia

AU - Al-Jamal, Khuloud

AU - Smith, David Kelham

N1 - ©2001, The Authors.

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. We therefore tested this system 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 indicated that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrated that the nasal delivery of a gel loaded with 3H-labelled L-DOPA out-performed a simple intranasal L-DOPA solution. This was attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It was 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. We therefore tested this system 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 indicated that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrated that the nasal delivery of a gel loaded with 3H-labelled L-DOPA out-performed a simple intranasal L-DOPA solution. This was attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It was 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.

U2 - 10.1002/advs.202101058

DO - 10.1002/advs.202101058

M3 - Article

SN - 2198-3844

VL - 8

JO - Advanced Science

JF - Advanced Science

IS - 14

M1 - 2101058

ER -