Topic definition: This literature review aims to update the current knowledge on toxicity of chitosan nanoparticles, compare the recent findings and identify the gaps with knowledge that is present for the chitosan nanoparticles.
Methods: The publications between 2010 and 2020 were searched in Science Direct, Pubmed.gov, Google Scholar, Research Gate, and ClinicalTrials.gov, according to the inclusion and exclusion criteria. 30 primary research studies were obtained from the literature review to compare the in vitro in vivo toxicity profiles among the chitosan nanoparticles.
Major highlights: Chitosan nanoparticles and other types of nanoparticles show cytotoxic effects on cancer cells while having minimal toxicity on normal cells. This apparent effect poses some considerations for use in incorporating cancer therapeutics into chitosan nanoparticles as an administration form. The concentration, duration of exposure, and pH of the solution can influence nanoparticle cytotoxicity, particularly in zebrafish. Different cell lines exhibit varying degrees of toxicity when exposed to nanoparticles, and of note are liver cells that show toxicity under exposure as indicated by increased alanine transaminase (ALT) levels. Aside from ALT, platelet aggregation can be considered a toxicity induced by chitosan nanoparticles. In addition, zebrafish cells experience the most toxicity, including organ damage, neurobehavioral impairment, and developmental abnormalities, when exposed to nanoparticles. However, nanoparticles may exhibit different toxicity profiles in different organisms, with brain toxicity and liver toxicity being present in zebrafish but not rats. Different organs exhibit varying degrees of toxicity, with the eye and mouth apparently having the lowest toxicity, while the brain, intestine, muscles and lung showing mixed results. Cardiotoxicity induced by chitosan nanoparticles was not observed in zebrafish embryos, and nanoparticles may reduce cardiotoxicity when delivering drug. Toxicity found in an organ may not necessarily mean that it is toxic towards all the cells found in that organ, as muscle toxicity was present when tested in zebrafish but not in C2C12 myoblast cells. Some of the studies conducted may have limitations that need to be reconsidered to account for differing results, with some examples being two experiments done on HeLa cells where one study concluded chitosan nanoparticles were toxic to the cells while the other seems to have no toxicity present. With regards to LD50, one study has stated the concentration of 64.21 mg/ml was found. Finally, smaller nanoparticles generally exhibit higher toxicity in cells compared to larger nanoparticles.
Scope for future work: This literature review did not uncover any published clinical trials with available results. Subsequent research endeavors should prioritize conducting clinical trials involving human volunteers to directly assess toxicity, rather than relying on cell or animal models.
Keywords: Cell lines; Chitosan; Deacetylation; Nanoparticles.
© 2023 The Authors.