Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 89, Issue -, Pages 206-218Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2016.04.076
Keywords
Quetiapine; Chitosan nanoparticles; Nose to brain delivery
Funding
- Lady Tata Memorial Trust (Bombay, India)
- Department of Science and Technology, Delhi, India [IFA-LSBM-13]
- Govt. of Gujarat
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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., X-1-Concentration of chitosan, X-2-Concentration of sodium tripolyphosphate and X-3-Volume of sodium tripolyphosphate were taken to investigate their effect on dependent variables (Y-1-Size, Y-2-PDI and Y-3-%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 +/- 7.45 nm, 0.252 +/- 1 0.064, 89.93 +/- 3.85% and 65.24 +/- 15.26% 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. (C) 2016 Elsevier B.V. All rights reserved.
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