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Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study

Authors Alam S, Khan ZI, Mustafa G, Kumar M, Islam F, Bhatnagar A, Ahmad FJ

Received 25 June 2012

Accepted for publication 3 August 2012

Published 9 November 2012 Volume 2012:7 Pages 5705—5718

DOI https://doi.org/10.2147/IJN.S35329

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Sanjar Alam,1 Zeenat I Khan,1 Gulam Mustafa,1 Manish Kumar,2 Fakhrul Islam,3 Aseem Bhatnagar,4 Farhan J Ahmad1

1Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India; 2Advanced Instrumentation Research Facility, Jawaharlal Nehru University, New Delhi, India; 3Department of Medical Elementology and Toxicology, Neurotoxicology Laboratory, Jamia Hamdard, Hamdard Nagar, New Delhi, India; 4Government of India, Ministry of Defence, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Marg, Delhi, India

Abstract: Chitosan (CS) nanoparticles of thymoquinone (TQ) were prepared by the ionic gelation method and are characterized on the basis of surface morphology, in vitro or ex vivo release, dynamic light scattering, and X-ray diffractometry (XRD) studies. Dynamic laser light scattering and transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. The results showed that the particle size of the formulation was significantly affected by the drug:CS ratio, whereas it was least significantly affected by the tripolyphosphate:CS ratio. The entrapment efficiency and loading capacity of TQ was found to be 63.3% ± 3.5% and 31.23% ± 3.14%, respectively. The drug-entrapment efficiency and drug-loading capacity of the nanoparticles appears to be inversely proportional to the drug:CS ratio. An XRD study proves that TQ dispersed in the nanoparticles changes its form from crystalline to amorphous. This was further confirmed by differential scanning calorimetry thermography. The flat thermogram of the nanoparticle data indicated that TQ formed a molecular dispersion within the nanoparticles. Optimized nanoparticles were evaluated further with the help of scintigraphy imaging, which ascertains the uptake of drug into the brain. Based on maximum concentration, time-to-maximum concentration, area-under-curve over 24 hours, and elimination rate constant, intranasal TQ-loaded nanoparticles (TQ-NP1) proved more effective in brain targeting compared to intravenous and intranasal TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the mucoadhesive properties of TQ-NP1.

Keywords: thymoquinone, chitosan, nanoparticles, nose-to-brain targeting, gamma scintigraphy

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