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

Abstract

IntroductionPolymeric 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.MethodsNanoparticles 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 discussionThe 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.ConclusionIonically cross-linked chitosan nanoparticles are non-toxic and biocompatible drug delivery systems for sustained release of chemotherapeutic agents, such as docetaxel.

The Potential Cytotoxic Activity Enhancement of α-Mangostin in Chitosan-Kappa Carrageenan-Loaded Nanoparticle against MCF-7 Cell Line

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Fabrication, in vitro and ex vivo evaluation of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein

“…The procedure was repeated thrice ( n = 3) and then the samples were observed through a UV/Visible spectrophotometer (IRMECO, U2020, Germany) at 258.7 nm. The percent entrapment efficiency and drug loading capacity of liposomes and proliposomes were calculated by the following formula [ 23 ]: …”

A pH-sensitive nanocarrier based on BSA-stabilized graphene-chitosan nanocomposite for sustained and prolonged release of anticancer agents

“…In this way, Mahmood et al prepared chitosan-tripolyphosphate nanoparticles for the sustained release of docetaxel by modifications of the Calvo ionic-gelation method. The results showed faster release in the early hours of the nanoparticle administration, followed by the sustained release in just 24 h at pH 7.4 41 . The release curve exhibited that 60% of indole-3-acetic acid was released in the first 8 h. Afterward, the sustained release within 24 h leads to the release of 100% indole-3-acetic acid 42 .…”