Application of Box-Behnken design for optimization and development of quetiapine fumarate loaded chitosan nanoparticles for brain delivery via intranasal route
Abstract
The objective of the present investigation was to optimize and develop quetiapine fumarate (QF) loaded chitosan nanoparticles (QF-NP) by ionic gelation method using Box-Behnken design. Three independent variables viz., X1-Concentration of chitosan, X2-Concentration of sodium tripolyphosphate and X3-Volume of sodium tripolyphosphate were taken to investigate their effect on dependent variables (Y1-Size, Y2-PDI and Y3-%EE). Optimized formula of QF-NP was selected from the design space which was further evaluated for physicochemical, morphological, solid state characterization, nasal diffusion and in-vivo distribution for brain targeting following non-invasive intranasal administration. The average particle size, PDI, %EE and nasal diffusion were found to be 131.08±7.45nm, 0.252±0.064, 89.93±3.85% and 65.24±5.26% respectively. Neither toxicity nor structural damage on nasal mucosa was observed upon histopathological examination. Significantly higher brain/blood ratio and 2 folds higher nasal bioavailability in brain with QF-NP in comparison to drug solution following intranasal administration revealed preferential nose to brain transport bypassing blood-brain barrier and prolonged retention of QF at site of action suggesting superiority of chitosan as permeability enhancer. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery.
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Chitosan shows strong mucoadhesive properties due to its cationic nature and interaction with net negatively charged intestinal mucus layer, enhancing its residence time in the colon and drug diffusion gradient, leading to increased absorption.
“Chitosan shows strong mucoadhesive properties due to its cationic nature and interaction with net negatively charged intestinal mucus layer, enhancing its residence time in the colon and drug diffusion gradient, leading to increased absorption (Shah et al., 2016).”
From pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. (2023) · cites this paper as Shah et al., 2016
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- Authors
- Shah, B., Khunt, D., Misra, M., & Padh, H.
- Affiliations
- B. V. Patel Pharmaceutical Education and Research Development Centre (IN)
- National Institute of Pharmaceutical Education and Research - Ahmedabad (IN)
- Sardar Patel University (IN)
- Corresponding author
- Misra, Manju
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 89
- Pages
- 206-218
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W2381160200
- Cited by
- 112
- References
- 38
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 15 · 2023: 13 · 2022: 14 · 2021: 11 · 2020: 18 · 2019: 7 · 2018: 7 · 2017: 3 · 2016: 1
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lady Tata Memorial Trust
- Department of Science and Technology, Government of Kerala
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- quetiapine, chitosan nanoparticles, intranasal drug delivery, brain targeting, ionic gelation, Box-Behnken design, sodium tripolyphosphate, brain-to-blood ratio, blood-brain barrier bypass, particle size and polydispersity, encapsulation efficiency
- MeSH terms
- Quetiapine Fumarate, Administration, Intranasal, Animals, Biological Availability, Brain, Drug Carriers, Drug Compounding, Factor Analysis, Statistical, Goats, Nasal Mucosa, Particle Size, Permeability, Polyphosphates, Tissue Distribution, Antipsychotic Agents, Rats, Sprague-Dawley, Area Under Curve, Tissue Culture Techniques, Chitosan, Nanoparticles
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