“The Good, the Bad and the Ugly” of Chitosans

Abstract

The objective of this paper is to emphasize the fact that while consistent interest has been paid to the industrial use of chitosan, minor attention has been devoted to spread the knowledge of a good characterization of its physico-chemical properties. Therefore, the paper attempts to critically comment on the conflicting experimental results, highlighting the facts, the myths and the controversies. The goal is to indicate how to take advantage of chitosan versatility, to learn how to manage its variability and show how to properly tackle some unexpected undesirable features. In the sections of the paper various issues that relate chitosan properties to some basic features and to advanced solutions and applications are presented. The introduction outlines some historical pioneering works, where the chemistry of chitosan was originally explored. Thereafter, particular reference is made to analytical purity, characterization and chain modifications. The macromolecular characterization is mostly related to molecular weight and to degree of acetylation, but also refers to the conformational and rheological properties and solution stability. Then, the antimicrobial activity of chitosan in relation with its solubility is reviewed. A section is dedicated to the formulation of chitosan biomaterials, from gel to nanobeads, exploring their innovative application as active carrier nanoparticles. Finally, the toxicity issue of chitosan as a polymer and as a constructed nanomaterial is briefly commented in the conclusions.

An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery

“…Similarly, lung infections and colon diseases can be effectively targeted locally with chitosan NP. A chitosan-based nasal formulation of morphine (Rylomine TM ) is currently in Phase 2 clinical trials (UK and EU) and Phase 3 clinical trials in the U.S. We anticipate that when it reaches the market it will pave way for similar products in the near future as well as assist in discerning any unanticipated effects in humans [120]. And, while not specifically addressed herein, we look forward to additional advances in the use of chitosan nanoparticles in targeted cancer theranostics, dermatologic applications and targeted parenteral drug delivery systems [121,122,123,124].…”

“…To date, chitosan has shown little or no toxicity in animal models and there have been no reports of major adverse effects in healthy human volunteers but clinical data are lacking. Even though chitosan is approved in dietary use, wound dressing applications and cartilage formulations, as of this writing there is not yet a chitosan-based drug formulation approved for mass marketing [120]. Issues regarding scale up of fabrication methods will likely be informed by that of other polymeric formulations.…”

An Overview of Various Carriers for siRNA Delivery

“…Furthermore, because chitosan is positively charged, it has the ability to interact with and protect negatively charged nucleic acids such as siRNA. [24,25] However, a significant challenge to chitosan research is its variability in composition and molecular weight, which makes it difficult to understand which properties are associated with which effect. [25] Chitosan transfection efficiency is sensitive to the pH of its surroundings, and as pH cannot be controlled in vivo, more research needs to be conducted to alleviate potential problems with the vector's transfection efficiency.…”

“…[24,25] However, a significant challenge to chitosan research is its variability in composition and molecular weight, which makes it difficult to understand which properties are associated with which effect. [25] Chitosan transfection efficiency is sensitive to the pH of its surroundings, and as pH cannot be controlled in vivo, more research needs to be conducted to alleviate potential problems with the vector's transfection efficiency. Additionally, to optimize chitosan-delivery for siRNA, the ratio of the siRNA should be 5 to 10 times less than of the chitosan.…”

“…Similar to chitosan nanocarriers, dendrimers are biocompatible and have negligible immunogenicity; however, unlike unmodified chitosan, they are also water soluble. [25,30,31] Dendrimers are also similar to lipid-based vectors due to high cytotoxicity being associated with not only cationic lipid-based vectors but cationic dendrimers as well. [17,22,30] However, dendrimers can also be modified through PEGylation to not only increase the duration of its circulation in the blood but also to decrease its toxicity and increase its transfection efficacy.…”