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Ionically Cross-Linked Chitosan Nanoparticles for Sustained Delivery of Docetaxel: Fabrication, Post-Formulation and Acute Oral Toxicity Evaluation

Authors Mahmood MA, Madni A, Rehman M, Rahim MA, Jabar A

Received 24 September 2019

Accepted for publication 2 December 2019

Published 20 December 2019 Volume 2019:14 Pages 10035—10046


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo

Muhammad Ahmad Mahmood,1,2 Asadullah Madni,1 Mubashar Rehman,3 Muhammad Abdur Rahim,1 Abdul Jabar1

1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; 2Drug Testing Laboratory, Bahawalpur 63100, Pakistan; 3Faculty of Pharmacy, University of Central Punjab, Lahore 54000, Pakistan

Correspondence: Asadullah Madni
Department of Pharmacy, The Islamia University of Bahawalpur, Khawaja Fareed Campus, Railway Road, Bahawalpur, Punjab, Pakistan
Tel +92 62 925 5243
Fax +92 62 925 5565

Introduction: Polymeric nanoparticles are potential carriers for the efficient delivery of hydrophilic and hydrophobic drugs due to their multifaceted applications. Docetaxel is relatively less hydrophobic and twice as potent as paclitaxel. Like other taxane chemotherapeutic agents, docetaxel is not well tolerated and shows toxicity in the patients. Nanoencapsulation of potent chemotherapeutic agents has been shown to improve tolerability and therapeutic outcome. Therefore, the present study was designed to fabricate chitosan and sodium tripolyphosphate (STPP) based on ionically cross-linked nanoparticles for sustained release of docetaxel.
Methods: Nanoparticles were prepared by the ionic-gelation method by dropwise addition of the STPP solution into the chitosan solution in different ratios. CNPs were characterized for post-formulation parameters like size, zeta potential, scanning electron microscope (SEM), FTIR, DSC/TGA, pXRD, and in-vitro drug release, as well as for acute oral toxicity studies in Wistar rats.
Results and discussion: The optimized docetaxel loaded polymeric nanoparticles were in the size range (172.6nm–479.65 nm), and zeta potential (30.45–35.95 mV) required to achieve enhanced permeation and retention effect. In addition, scanning electron microscopy revealed rough and porous surface, whereas, FTIR revealed the compatible polymeric nanoparticles. Likewise, the thermal stability was ensured through DSC and TG analysis, and powder X-ray diffraction analysis exhibited solid-state stability of the docetaxel loaded nanoparticles. The in-vitro drug release evaluation in phosphate buffer saline (pH 7.4) showed sustained release pattern, i.e. 51.57–69.93% within 24 hrs. The data were fitted to different release kinetic models which showed Fickian diffusion as a predominant release mechanism (R2= 0.9734–0.9786, n= 0.264–0.340). Acceptable tolerability was exhibited by acute oral toxicity in rabbits and no abnormality was noted in growth, behavior, blood biochemistry or histology and function of vital organs.
Conclusion: Ionically cross-linked chitosan nanoparticles are non-toxic and biocompatible drug delivery systems for sustained release of chemotherapeutic agents, such as docetaxel.

Keywords: tripolyphosphate, ionic gelation, sustained release, targeting, biocompatible, biodegradable

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