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Chitosan Chemistry and Pharmaceutical Perspectives

A major reference in the early chitin bibliography was a book written in 1951

“primarily for entomologists and other invertebrate zoologists”, but also, in the author’s hope,

for chemists: the perception of the need for more chemical information was manifest in the book preface.

In the review article below, recent trends in the development of chitin science are recalled.



Chitosan Chemistry and Pharmaceutical Perspectives

 

M. N. V. R. Kumar, R. A. A. Muzzarelli,

C. Muzzarelli, H. Sashiwa and A. J. Domb



Published in:

Chemical Reviews, 104, 6017-6084 (2004)

American Chemical Society, Washington



 

When Richards published his book in 1951, the chitin chemistry developed to that date was inadequate: for instance color tests were not specific enough to provide a reliable picture of the distribution and location of chitin in living organisms.

Specific and accurate techniques for chitin identification became accessible with the improvement of the x-ray diffraction methods by Rudall (1963) and the enzymatic method of Jeuniaux (1963). Remarkably, the book edited by Hepburn (1976) opened with a biographical chapter honoring Richards, followed by a contribution by Rudall and by a chapter by Muzzarelli on the biochemical modifications of chitin. That was a real turning point.

The books by Hepburn (1976) and by Neville (1975) were immediately followed by the first book on chitin authored by Muzzarelli (1977) and, the same year, by the 1st International Conference on Chitin and Chitosan (proceedings published by Muzzarelli and Pariser, 1978).

In the early times, the interest in chitin was cultivated mainly by zoologists, marine entomologists and physiologists, but, in the late seventies, chemists all over the world devoted attention to chitin. In particular, it was immediately realized that chitin was an abundant source of chitosan, the unique cationic polysaccharide (as opposed to a variety of easily accessible anionic polysaccharides), and, as such, was superior to man-made cationic derivatives of cellulose and starch. The inherent biodegradability of chitin and chitosan was interpreted as an appealing characteristic property rather than a drawback (at a time when artificial polymers as nylon were celebrated for their inertness).

The development of chitinology, in the last quarter of the century, followed periods dominated by specific topics, that can be roughly related to: i) technological advances (spinning, coloring, uptake of soluble species, cosmetic functional ingredients); ii) biochemical significance (blood coagulation, wound healing, bone regeneration, immunoadjuvant activity); iii) inhibition of the biosynthesis (insecticides); iv) chitin enzymology (isolation and characterization of chitinases, their molecular biology, biosynthesis, hydrolases with unspecific chitinolytic activity); v) combinations of chitosan with natural and synthetic polymers (grafting, polyelectrolyte complexation; blends, coatings; vi) use of chitosan as a dietary supplement and a food preservative (anticholesterolemic dietary products, antimicrobial coatings for grains and exotic fruits). Each of these topics had a “high season” that produced a burst of publications; as a whole a deeper knowledge on chitosan was obtained, but also a fruitful integration of interdisciplinary interests.

Drug delivery seems to be today the topic that attracts more attention: it finds scientific support in the basic knowledge on chitin, mainly chemical modifications, biodegradation, effects on various tissues, distribution to various body organs, mucoadhesion, association of chitosan with inorganic compounds, and advanced technological transformations.

The key considerations that justify this interest are that chitosan is biocompatible and does not elicit adverse reactions when in contact with human cells; it can be degraded by ubiquitous enzyme in the human body, and oligomers and monomers are useful biochemical signals (activation of macrophages, stimulation of hyaluronan synthesis), and moreover they provide building blocks for the reconstruction of extracellular matrix components. On the other hand, chitosan is recognized by tumor cells and therefore it can bring drugs to their target selectively.

Because chitosan is a safe and friendly substance for the human organism, medical and pharmaceutical applications can be easily developed with the joint contribution of specialists in various fields.

 

fig42

Figure 42. Healing of the meniscal lesions in the rabbit. (top) Control showing the poorly organized collagen network. (bottom) After medication with methylpyrrolidinone chitosan (45 days a.s.), vascular structures and fibroblastic elements lead to complete repair.

 


CITATIONS

In the period June 2005 - June 2009, this article was cited in 242 articles, many of which have been further cited in most recent articles.

 

http://pubs.acs.org/doi/abs/10.1021/cr030441b