Characteristics and application of chitosan in pharmaceutical/biomedical preparations

Abstract

Chitosans are binary linear heteropolysaccharides derived from chitin by its partial deacetylation. Due to unique cationic nature these biopolymers have enormous potential in pharmacy and biomedicine. This potential is improved by their chemical versatility (molecular mass and degree of deacetylation) and possibility of chemical derivatisation. Numerous biological activities of chitosans such as mucoadhesivity, hemostatic, hypocholesterolemic and antimicrobial activity are based on their specific polycationic nature. Gel-forming, cross-linking and polyelectrolyte complex forming ability make chitosans suitable for design of colloidal drug delivery systems, such as dendrimers, liposomes, micelles, micro- and nanoparticles. Chitosans as well as their derivates are used in commercially available wound dressings due to their hemostatic activity and ability to stimulate cell proliferation, tissue regeneration process and mild local analgesic effect. The use of chitosans as dietary supplements has been approved in many countries since their effect on maintenance of normal blood LDL cholesterol concentrations has been confirmed. Chitosan derivatives, such as N-carboxymethyl chitosan are commonly used in cosmetics, due to their gel and film forming ability, pleasant, hydrating, softening, and protecting effect on skin. There is a special interest for use of chitosans in tissue engineering due to their ability to form biocompatible porous tridimensional gel networks, whose porosity and in vivo degradation can be controlled. Lack of registered chitosan based products is a consequence of its unsolved regulatory status. Namely, its chemical versatility may affect biodistribution, biodegradation and toxicological profiles, thus making regulatory approval of chitosans as GRAS materials quite difficult.

Hitozani su linearni, binarni heteropolisaharidi dobijeni parcijalnom deacetilacijom hitina. Kao katjonski polisaharidi prirodnog porekla imaju veliki potencijal za primenu u oblasti farmacije i biomedicine. Tome dodatno doprinosi njihova strukturna raznovrsnost u pogledu molekulske mase i stepena deacetilacije, ali i mogućnost hemijske derivatizacije. Specifična polikatjonska priroda ovih biopolimera odgovorna je za njihova brojna biološka svojstva poput mukoadhezivnosti, hemostatičnog, antimikrobnog i hipoholesterolemičnog delovanja. Zahvaljujući gelirajućim sposobnostima, mogućnosti umrežavanja i građenja reverzibilnih polielektrolitnih kompleksa sa polianjonima, hitozani se koriste za izradu koloidnih nosača lekovitih supstanci poput dendrimera, liposoma, micela, mikro- i nanočestica. Hitozani i njihovi derivati ulaze u sastav komercijalno dostupnih preparata/sredstava za zarastanje rana zahvaljujući stimulaciji proliferacije ćelija i obnavljanja tkiva, hemostatskom i blagom lokalnom analgetičkom delovanju. Upotreba hitozana kao dodatka ishrani odobrena je u mnogim zemljama, a potvrđen je njihov uticaj na održavanje normalnog nivoa serumskog LDL holesterola. Derivati hitozana, poput N-karboksimetilhitozana koriste se u kozmetičkim proizvodima jer poseduju sposobnosti geliranja i formiranja filma, stvaraju prijatan osećaj na koži, omekšavaju, vlaže i štite kožu od spoljašnjih uticaja. Posebnu pažnju hitozani privlače u oblasti tkivnog inženjerstva zahvaljujući mogućnosti obrazovanja biokompatibilnih poroznih trodimenzionalnih mreža čiju je poroznost i brzinu degradacije u in vivo uslovima moguće kontrolisati. Širu primenu hitozana trenutno ograničava nerešen regulatorni status, jer strukturna raznovrsnost hitozana ima za posledicu razlike u biodistribuciji, biodegradaciji i toksikološkim profilima, što značajno otežava dobijanje GRAS statusa.