Quercetin-Loaded Nanostructured Lipid Carrier In Situ Gel for Brain Targeting Through Intranasal Route: Formulation, In Vivo Pharmacokinetic and Pharmacodynamic Studies
Quercetin (QT) shows potential for protecting against neurodegenerative diseases like Alzheimer’s. However, its limited bioavailability and instability in physiological pH hinder its clinical use. The purpose of this work is to construct QT-filled nanostructured lipid carriers (QT-NLC) intranasal in...
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| Published in | AAPS PharmSciTech Vol. 25; no. 2; p. 30 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
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Springer International Publishing
05.02.2024
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| Abstract | Quercetin (QT) shows potential for protecting against neurodegenerative diseases like Alzheimer’s. However, its limited bioavailability and instability in physiological pH hinder its clinical use. The purpose of this work is to construct QT-filled nanostructured lipid carriers (QT-NLC) intranasal
in situ
gel to enhance pharmacokinetic and pharmacodynamic performance. NLCs were developed using a melt emulsification–high-pressure homogenization and were optimized using design expert software with the Box-Behnken design. NLCs were then incorporated into an
in situ
gel based on Lutrol F127 and further characterized. The pharmacodynamics of the formulation was evaluated in neurodegeneration induced by trimethyl tin (TMT) Wistar rats. The optimized QT
in situ
gel had spherical shape, entrapment efficiency of 96.1 ± 4.40%, and
in vitro
drug release of 83.74 ± 1.40%. The mean particle size was 123.3 ± 5.46 nm. After intranasal administration,
in vivo
single-dose pharmacokinetic studies demonstrated a significant therapeutic concentration of drug in CNS, having C
max
183.41 ± 11.76 ng/mL and T
max
of 2 h. The more brain targeting efficiency of NLCs was proved by the developed QT
in situ
gel, which had a higher drug targeting efficiency (DTE) of 117.47% and drug targeting potential (DTP) of 88.9%. As compared to the neurodegeneration control group, the QT
in situ
gel–treated group had significantly decreased escape latency and pathlength. Biochemical analysis and histological investigations demonstrated that QT
in situ
gel exhibited superior anti-Alzheimer’s potential compared to standard drug, donepezil. The promising results of the developed and optimized intranasal QT
in situ
gel suggest its potential and can be used in Alzheimer’s disease management.
Graphical Abstract |
|---|---|
| AbstractList | Quercetin (QT) shows potential for protecting against neurodegenerative diseases like Alzheimer's. However, its limited bioavailability and instability in physiological pH hinder its clinical use. The purpose of this work is to construct QT-filled nanostructured lipid carriers (QT-NLC) intranasal in situ gel to enhance pharmacokinetic and pharmacodynamic performance. NLCs were developed using a melt emulsification-high-pressure homogenization and were optimized using design expert software with the Box-Behnken design. NLCs were then incorporated into an in situ gel based on Lutrol F127 and further characterized. The pharmacodynamics of the formulation was evaluated in neurodegeneration induced by trimethyl tin (TMT) Wistar rats. The optimized QT in situ gel had spherical shape, entrapment efficiency of 96.1 ± 4.40%, and in vitro drug release of 83.74 ± 1.40%. The mean particle size was 123.3 ± 5.46 nm. After intranasal administration, in vivo single-dose pharmacokinetic studies demonstrated a significant therapeutic concentration of drug in CNS, having Cmax 183.41 ± 11.76 ng/mL and Tmax of 2 h. The more brain targeting efficiency of NLCs was proved by the developed QT in situ gel, which had a higher drug targeting efficiency (DTE) of 117.47% and drug targeting potential (DTP) of 88.9%. As compared to the neurodegeneration control group, the QT in situ gel-treated group had significantly decreased escape latency and pathlength. Biochemical analysis and histological investigations demonstrated that QT in situ gel exhibited superior anti-Alzheimer's potential compared to standard drug, donepezil. The promising results of the developed and optimized intranasal QT in situ gel suggest its potential and can be used in Alzheimer's disease management.Quercetin (QT) shows potential for protecting against neurodegenerative diseases like Alzheimer's. However, its limited bioavailability and instability in physiological pH hinder its clinical use. The purpose of this work is to construct QT-filled nanostructured lipid carriers (QT-NLC) intranasal in situ gel to enhance pharmacokinetic and pharmacodynamic performance. NLCs were developed using a melt emulsification-high-pressure homogenization and were optimized using design expert software with the Box-Behnken design. NLCs were then incorporated into an in situ gel based on Lutrol F127 and further characterized. The pharmacodynamics of the formulation was evaluated in neurodegeneration induced by trimethyl tin (TMT) Wistar rats. The optimized QT in situ gel had spherical shape, entrapment efficiency of 96.1 ± 4.40%, and in vitro drug release of 83.74 ± 1.40%. The mean particle size was 123.3 ± 5.46 nm. After intranasal administration, in vivo single-dose pharmacokinetic studies demonstrated a significant therapeutic concentration of drug in CNS, having Cmax 183.41 ± 11.76 ng/mL and Tmax of 2 h. The more brain targeting efficiency of NLCs was proved by the developed QT in situ gel, which had a higher drug targeting efficiency (DTE) of 117.47% and drug targeting potential (DTP) of 88.9%. As compared to the neurodegeneration control group, the QT in situ gel-treated group had significantly decreased escape latency and pathlength. Biochemical analysis and histological investigations demonstrated that QT in situ gel exhibited superior anti-Alzheimer's potential compared to standard drug, donepezil. The promising results of the developed and optimized intranasal QT in situ gel suggest its potential and can be used in Alzheimer's disease management. Quercetin (QT) shows potential for protecting against neurodegenerative diseases like Alzheimer’s. However, its limited bioavailability and instability in physiological pH hinder its clinical use. The purpose of this work is to construct QT-filled nanostructured lipid carriers (QT-NLC) intranasal in situ gel to enhance pharmacokinetic and pharmacodynamic performance. NLCs were developed using a melt emulsification–high-pressure homogenization and were optimized using design expert software with the Box-Behnken design. NLCs were then incorporated into an in situ gel based on Lutrol F127 and further characterized. The pharmacodynamics of the formulation was evaluated in neurodegeneration induced by trimethyl tin (TMT) Wistar rats. The optimized QT in situ gel had spherical shape, entrapment efficiency of 96.1 ± 4.40%, and in vitro drug release of 83.74 ± 1.40%. The mean particle size was 123.3 ± 5.46 nm. After intranasal administration, in vivo single-dose pharmacokinetic studies demonstrated a significant therapeutic concentration of drug in CNS, having C max 183.41 ± 11.76 ng/mL and T max of 2 h. The more brain targeting efficiency of NLCs was proved by the developed QT in situ gel, which had a higher drug targeting efficiency (DTE) of 117.47% and drug targeting potential (DTP) of 88.9%. As compared to the neurodegeneration control group, the QT in situ gel–treated group had significantly decreased escape latency and pathlength. Biochemical analysis and histological investigations demonstrated that QT in situ gel exhibited superior anti-Alzheimer’s potential compared to standard drug, donepezil. The promising results of the developed and optimized intranasal QT in situ gel suggest its potential and can be used in Alzheimer’s disease management. Graphical Abstract Quercetin (QT) shows potential for protecting against neurodegenerative diseases like Alzheimer's. However, its limited bioavailability and instability in physiological pH hinder its clinical use. The purpose of this work is to construct QT-filled nanostructured lipid carriers (QT-NLC) intranasal in situ gel to enhance pharmacokinetic and pharmacodynamic performance. NLCs were developed using a melt emulsification-high-pressure homogenization and were optimized using design expert software with the Box-Behnken design. NLCs were then incorporated into an in situ gel based on Lutrol F127 and further characterized. The pharmacodynamics of the formulation was evaluated in neurodegeneration induced by trimethyl tin (TMT) Wistar rats. The optimized QT in situ gel had spherical shape, entrapment efficiency of 96.1 ± 4.40%, and in vitro drug release of 83.74 ± 1.40%. The mean particle size was 123.3 ± 5.46 nm. After intranasal administration, in vivo single-dose pharmacokinetic studies demonstrated a significant therapeutic concentration of drug in CNS, having C 183.41 ± 11.76 ng/mL and T of 2 h. The more brain targeting efficiency of NLCs was proved by the developed QT in situ gel, which had a higher drug targeting efficiency (DTE) of 117.47% and drug targeting potential (DTP) of 88.9%. As compared to the neurodegeneration control group, the QT in situ gel-treated group had significantly decreased escape latency and pathlength. Biochemical analysis and histological investigations demonstrated that QT in situ gel exhibited superior anti-Alzheimer's potential compared to standard drug, donepezil. The promising results of the developed and optimized intranasal QT in situ gel suggest its potential and can be used in Alzheimer's disease management. |
| ArticleNumber | 30 |
| Author | Pokharkar, Varsha Sonawane, Devika |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38316672$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1186_s12871_024_02876_0 crossref_primary_10_1016_j_arr_2025_102665 crossref_primary_10_1016_j_mtbio_2025_101518 crossref_primary_10_1002_mame_202400356 |
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| Keywords | alzheimer’s disease intranasal delivery quercetin NLCs gel In situ gel |
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| SubjectTerms | Administration, Intranasal Animals Biochemistry Biomedical and Life Sciences Biomedicine Biotechnology Brain Drug Carriers - chemistry Lipids - chemistry Nanostructures - chemistry Particle Size Pharmacology/Toxicology Pharmacy Quercetin Rats Rats, Wistar Research Article |
| Title | Quercetin-Loaded Nanostructured Lipid Carrier In Situ Gel for Brain Targeting Through Intranasal Route: Formulation, In Vivo Pharmacokinetic and Pharmacodynamic Studies |
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