Thermoresponsive Gel for Sustained Nanoliposome-Mediated Nose-to-Brain Drug Delivery
4 affiliations
- 1Institute of Pharmaceutical Technology, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North Macedonia
- 2Department of Animal and Human Physiology, Faculty of Biology, Sofia University “St. Kliment Ohridski”, 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria
- 3Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia
- 4Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 23, 1113 Sofia, Bulgaria
Abstract
Nose-to-brain drug delivery represents a promising non-invasive strategy for improving CNS targeting. However, conventional liquid formulations are limited by rapid mucociliary clearance and short mucosal residence time. This study developed a thermoresponsive in situ gel incorporating indocyanine green (ICG)-loaded nanoliposomes and evaluated its potential to enhance and modulate the ICG-associated brain distribution after intranasal administration of the formulation. ICG-loaded nanoliposomes were prepared using a modified thin-film hydration method and incorporated into a poloxamer-based gel containing hyaluronic acid and Carbomer 940 as mucoadhesive components. The nanoliposomes exhibited a mean particle size of 124 ± 3.25 nm, a unimodal size distribution, and a high ICG encapsulation efficiency of 93.33%. Rheological analysis confirmed a temperature-triggered sol-to-gel transition at the physiological nasal temperature (~32 °C), shear-thinning behavior, and rapid structural recovery suitable for intranasal application. Ex vivo fluorescence imaging in rats demonstrated distinct biodistribution profiles for the ICG-associated signal delivered via the liquid nanoliposomes and gel-incorporated nanoliposomes. Although the liquid liposomes showed faster early signal at 4 h, the gel formulation produced stronger and more sustained brain fluorescence at later time points. At 8 h and 24 h, whole-brain fluorescence was approximately twofold higher with the gel formulation than with the liquid liposomes formulation. These findings indicate that this thermoresponsive gel enhances nasal retention and may modulate the delivery profile of the nose-to-brain transport, supporting its potential as a platform for CNS-targeted delivery and the development of more effective therapies for neurodegenerative diseases.
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BibTeX
@article{mihailova2026thermoresponsive,
title = {{Thermoresponsive Gel for Sustained Nanoliposome-Mediated Nose-to-Brain Drug Delivery}},
author = {Ljubica Mihailova and Dushko Shalabalija and Marija Glavas Dodov and Milena Mishonova and Lea Koceva and Neli Raikova and Mitko Mladenov and Hristo Gagov and Jana Tchekalarova and Polina Petkova-Kirova and Iliyana Sazdova},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219759},
url = {https://www.mdpi.com/1422-0067/27/21/9759},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Thermoresponsive Gel for Sustained Nanoliposome-Mediated Nose-to-Brain Drug Delivery
AU - Ljubica Mihailova
AU - Dushko Shalabalija
AU - Marija Glavas Dodov
AU - Milena Mishonova
AU - Lea Koceva
AU - Neli Raikova
AU - Mitko Mladenov
AU - Hristo Gagov
AU - Jana Tchekalarova
AU - Polina Petkova-Kirova
AU - Iliyana Sazdova
PY - 2026
DA - 2026/10/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219759
UR - https://www.mdpi.com/1422-0067/27/21/9759
AB - Nose-to-brain drug delivery represents a promising non-invasive strategy for improving CNS targeting. However, conventional liquid formulations are limited by rapid mucociliary clearance and short mucosal residence time. This study developed a thermoresponsive in situ gel incorporating indocyanine green (ICG)-loaded nanoliposomes and evaluated its potential to enhance and modulate the ICG-associated brain distribution after intranasal administration of the formulation. ICG-loaded nanoliposomes were prepared using a modified thin-film hydration method and incorporated into a poloxamer-based gel containing hyaluronic acid and Carbomer 940 as mucoadhesive components. The nanoliposomes exhibited a mean particle size of 124 ± 3.25 nm, a unimodal size distribution, and a high ICG encapsulation efficiency of 93.33%. Rheological analysis confirmed a temperature-triggered sol-to-gel transition at the physiological nasal temperature (~32 °C), shear-thinning behavior, and rapid structural recovery suitable for intranasal application. Ex vivo fluorescence imaging in rats demonstrated distinct biodistribution profiles for the ICG-associated signal delivered via the liquid nanoliposomes and gel-incorporated nanoliposomes. Although the liquid liposomes showed faster early signal at 4 h, the gel formulation produced stronger and more sustained brain fluorescence at later time points. At 8 h and 24 h, whole-brain fluorescence was approximately twofold higher with the gel formulation than with the liquid liposomes formulation. These findings indicate that this thermoresponsive gel enhances nasal retention and may modulate the delivery profile of the nose-to-brain transport, supporting its potential as a platform for CNS-targeted delivery and the development of more effective therapies for neurodegenerative diseases.
SN - 1422-0067
ER -