The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
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 (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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Cites
Box-Behnken design: An alternative for the optimization of analytical methods
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Intranasal delivery to the central nervous system: Mechanisms and experimental considerations
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Nanoparticulate systems for brain delivery of drugs.
Kreuter, J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00122-8 · Cited by 1,107
Nanoparticulate systems for brain delivery of drugs
Kreuter, J. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.015 · Cited by 965
Fan, W., Yan, W., Xu, Z., & Ni, H. (2011) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2011.09.042 · Cited by 930
Atypical antipsychotics: Mechanism of action
Seeman, P. (2002) · The Canadian Journal of Psychiatry · doi:10.1177/070674370204700106 · Cited by 899
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Chitosan in nasal delivery systems for therapeutic drugs
Casettari, L., & Illum, L. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.05.003 · Cited by 448
Strategy for effective brain drug delivery
Alam, M. I., Beg, S., Samad, A., Baboota, S., Kohli, K., Ali, J., Ahuja, A., & Akbar, M. (2010) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2010.05.003 · Cited by 415
Mechanism and consequence of chitosan-mediated reversible epithelial tight junction opening
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Jeong, S., Jang, J.-H., & Lee, Y. (2022) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-022-00589-5 · Cited by 289
“The applied nanoformulations ranged from nanoparticles (Elnaggar et al. 2015; Eskandari et al. 2011; Hanafy et al. 2016; Meng et al. 2018; Salem et al. 2019; Seju et al. 2011; Shah et al. 2016; Zhang et al. 2014), to nanoemulsions (Abdou et al.”
BackgroundWang, Z., Xiong, G., Tsang, W. C., Schätzlein, A. G., & Uchegbu, I. F. (2019) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.119.258152 · Cited by 247
“09% when dosed as chitosan–tripolyphosphate nanoparticles (Shah et al., 2016).”
BackgroundNanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies
Pires, P. C., & Santos, A. O. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.11.047 · Cited by 228
Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier
Lee, D., & Minko, T. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13122049 · Cited by 227
Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders
Islam, S. U., Shehzad, A., Ahmed, M. B., & Lee, Y. S. (2020) · Molecules · doi:10.3390/molecules25081929 · Cited by 193
“Compared to an intranasal solution, quetiapine chitosan nanoparticles enhanced the drug delivery to the brain by 34% [179].”
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Metadata
- 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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