Chitosan-based drug nanocarriers: Where do we stand?

doi:10.1016/j.jconrel.2012.03.017

Journal of Controlled Release

Volume 161, Issue 2, 20 July 2012, Pages 496-504

https://doi.org/10.1016/j.jconrel.2012.03.017 Get rights and content

Abstract

Chitosan-based nanocarriers have become one of the most intensively studied transmucosal nanometric drug delivery platforms. This is due to a number of factors, including their simple and mild preparation technique as well as their capacity to associate macromolecules and facilitate their transport across mucosal barriers. In this review, we first describe our contribution to the origin of chitosan nanocarriers in the mid 90s, and summarize the early work that has impacted the development of this delivery technology. Secondly, we present our perspective regarding the potential of chitosan nanocarriers for some relevant applications: (i) vaccination, (ii) transmucosal protein delivery and (iii) gene therapy. Finally, we offer our perspective on the plausible advances in this area in the near future.

Graphical abstract

Section snippets

Biopharmaceutical and toxicological profile of chitosan

Chitosan (CS) is the common name of a linear, random copolymer of β-(1–4)-linked d-glucosamine and N-acetyl-d-glucosamine whose molecular structure comprises a linear backbone linked through glycosidic bonds. The basic amine groups of this polysaccharide are protonated and, thus positively charged in most physiological fluids. CS can be considered mostly hydrophilic, but the percentage of acetylated monomers and their distribution in the chains has a critical effect on its solubility and

Chitosan nanocarriers for drug delivery: the early years

The origin of polymer nanocarriers for drug delivery dates from the late 70s and is attributed to Peter Speiser [30], [31], [32]. One of the applications of these initial nanoparticle drug delivery systems made of polymethacrylates was to enhance the immunogenicity of antigens, in other words, to have an adjuvant effect [30]. Unfortunately, this novel research was not developed further due to the safety concerns associated to these nanoparticles. It was not until the early 90s when the idea of

Chitosan nanocarriers: main applications

As indicated in the previous section, the potential of CS nanocarrier technology has been reported for a variety of applications that include immunization [4], topical ocular/dermal drug delivery [5], transmucosal oral/nasal peptide absorption [3], anti-cancer drug delivery [57], brain delivery [49] and gene delivery [58]. For the sake of clarity and brevity this review will focus on the three following areas, which have received wide attention: antigen delivery, peptide delivery and gene

Conclusions

CS-based nanomedicine technology has reached considerable maturity in the last 15 years. There is now an extensive body of intellectual property related to CS based nanomedicines, and compelling evidence for the potential of CS nanocarriers for many challenging drug delivery applications. Along with this, there is also indicative data regarding CS biocompatibility, which further supports its potential use in nanomedicine. All this has resulted in commercially available CS based transfection

Acknowledgments

MGF thanks a contract from Programa Isidro Parga Pondal (Xunta de Galicia). The authors acknowledge financial support from Xunta de Galicia, Competitive Reference Groups (FEDER funds) and the Spanish Ministry of Science and Innovation, Programa de Investigación en Salud, Ref. PS09/01786, Ref PI081444 and Consolider Program, Ref. CSD2006-00012. We also acknowledge the help of Adam McGlone in the edition of the manuscript and Sara Vicente for help in the literature review.

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ReviewChitosan-based drug nanocarriers: Where do we stand?

Abstract

Graphical abstract

Section snippets

Biopharmaceutical and toxicological profile of chitosan

Chitosan nanocarriers for drug delivery: the early years

Chitosan nanocarriers: main applications

Conclusions

Acknowledgments

Adv. Drug Deliv. Rev.

Adv. Drug Deliv. Rev.

Adv. Drug Deliv. Rev.

Carbohydr. Res.

Biomaterials

Carbohydr. Polym.

Biomaterials

Int. J. Pharm.

Carbohydr. Polym.

Regul. Toxicol. Pharmacol.

J. Pharm. Sci.

Eur. J. Pharm. Sci.

J. Control. Release

Int. J. Pharm.

Colloids Surf. B

J. Pharm. Sci.

Eur. J. Pharm. Biopharm.

J. Control. Release

Eur. J. Pharm. Biopharm.

Int. J. Pharm.

Int. J. Pharm.

J. Control. Release

J. Drug Deliv. Sci. Technol.

Vaccine

Eur. J. Pharm. Biopharm.

J. Drug Deliv. Sci. Technol.

J. Control. Release

J. Control. Release

Vaccine

Eur. J. Pharm. Sci.

Vaccine

J. Control. Release

J. Control. Release

Eur. J. Pharm. Sci.

Int. J. Pharm.

J. Control. Release

J. Control. Release

Methods Enzymol.

J. Control. Release

Biomaterials

Biomaterials

Biomaterials

Eur. J. Pharm. Sci.

Acta Biomater.

Biomaterials

Methods Enzymol.

Eur. J. Pharm. Biopharm.

J. Control. Release

Eur. J. Pharm. Biopharm.

Biomaterials

Review
Chitosan-based drug nanocarriers: Where do we stand?