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Reduced Intestinal Toxicity of Docetaxel Loaded Into Mucoadhesive Nanoparticles, in Mouse Xenograft Model

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The present study demonstrated that the local intestinal toxicity of docetaxel (Dtx) was low when encapsulated in mucoadhesive nanoparticles composed of methyl-β-cyclodextrin (Me-β-CD)/poly(isobutylcyanoacrylate) coated with thiolated chitosan. The experiments were carried out using intestinal specimens collected from mice with a subcutaneous tumor at an advanced stage in order to obtain challenging pathological conditions. Surprisingly, both Dtx-loaded nanoparticles and unloaded-nanoparticles when administered orally induced a lower level of the intestinal and the colonic inflammations and ulcerations compared to intravenous (i.v) Dtx injection. The small intestine and the colon sections showed a preserved architecture, normal thickness of the mucosa, and normal viability. Furthermore, Dtx-loaded nanoparticles and unloaded-nanoparticles allowed decreasing the release of lactate dehydrogenase (LDH) enzyme of 22% and 43% respectively in comparison with the i.v. Taxotere® administration. These results indicated clearly that: (i) Me-CD/poly(isobutylcyanoacrylate) nanoparticles coated with thiolated chitosan reduced the local intestinal toxicity of Dtx, (ii) unloaded mucoadhesive nanoparticles had a protective effect allowing the preservation of intestinal integrity in mouse xenograft model.
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Keywords: DOCETAXEL; HISTOLOGICAL ANALYSIS; INTESTINAL TOXICITY; LDH; MUCOADHESION; PIBCA NANOPARTICLES; USSING CHAMBER

Document Type: Research Article

Publication date: December 1, 2012

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  • Journal of Colloid Science and Biotechnology is an international multidisciplinary peer- reviewed journal covering all aspects of colloid science including colloids preparation, characterization, structure-property relationships, spectroscopy, chemical and physical properties and applications of colloids in biotechnology, medicine and pharmaceuticals. This journal deals with interdisciplinary research areas of chemistry, physics, biology, materials science, polymer science, nanotechnology covering all topics related to colloids such as latexes, emulsions, suspensions, micellar systems, gels, composites, hybrids, surfactants, aerosols, foams, minerals, soft matter, microfluidics, encapsulation processes of active molecules, biomolecules, surfacial and interfacial processes, catalysis, electrochemistry, theoretical aspects, computer simulations and colloids in biotechnology and medicine.
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