Biocompatible non-covalent complexes of chitosan and different polymers: characteristics and application in drug delivery

Abstract

The formulation of biocompatible drug carriers based on cationic biopolymer chitosan and natural or synthetic polymers represents an important research interest. Therefore, this review aims to perceive their potential in drug delivery. The most investigated chitosan-based polymer blends are polyelectrolyte complexes (PECs) obtained by establishing ionic interactions with biocompatible polyanions as alginates, pectin, xanthan gum, carrageenan, carboxymethylcellulose, and collagen. Depending on the preparation conditions, PECs could be prepared in versatile forms including membranes/films, hydrogel beads, nanoparticles, and microparticles, to achieve controlled (e.g., extended, delayed, colon-specific and pH-dependent) drug delivery. PECs can encapsulate hydrophilic and lipophilic drug substances with different molecular weights. Drug encapsulation allows the preservation of their structure, activity, improvement in absorption efficiency, reduction in adverse effects and long-term stability in vitroand in vivo. The biocompatible structures as non-covalent chitosan-based complexes could be formed also by establishing hydrogen bonds, for example with poly(vinyl alcohol). The swelling of these complexes is not pH-dependent and encapsulated drug substances are often released by already known types of diffusion. Moreover, grafted chitosan derivatives (e.g., carboxymethyl chitosan, trimethyl chitosan, acrylated chitosan) are synthesized to improve water solubility at a wide pH range and enhance the encapsulation capacity of promising PEC-based drug carriers.

Formulacija biokompatibilnih nosača lekovitih supstanci na bazi katjonskog biopolimera hitozana i prirodnih ili sintetskih polimera predstavlja značajan istraživački interes. Stoga je cilj ovog rada sagledati njihovu potencijalnu primenu kao nosača lekovitih supstanci. Najistraženije blende polimera na bazi hitozana su polielektrolitni kompleksi (PEK) dobijeni uspostavljanjem jonskih interakcija sa biokompatibilnim polianjonima, npr. alginatom, pektinom, ksantan gumom, karagenanom, karboksimetilcelulozom i kolagenom. U zavisnosti od uslova pripreme, mogu se formulisati PEK u vidu membrana/filmova, hidrogelnih perli, nanočestica, mikročestica ili drugih tipova nosača, sa ciljem postizanja kontrolisanog (npr. produženog, odloženog, kolon-specifičnog i pH-zavisnog) oslobađanja lekovitih supstanci. PEK su pogodni za inkapsulaciju hidrofilnih ili lipofilnih lekovitih supstanci različitih molekulskih masa. Inkapsulacija obezbeđuje očuvanje njihove strukture, aktivnosti, poboljšanje apsorpcije, smanjenje štetnih efekata i dugoročnu stabilnost in vitro i in vivo. Biokompatibilne strukture nalik kompleksima na bazi hitozana mogu se formirati i uspostavljanjem vodoničnih veza, kao što je slučaj sa polivinil alkoholom. Njihovo bubrenje ne zavisi od pH. Inkapsulirane lekovite supstance se najčešće oslobađaju prema nekom od već poznatih tipova difuzije. Dodatno, različiti derivati hitozana (npr. karboksimetilhitozan, trimetilhitozan, akril derivati hitozana) sintetisani su radi poboljšanja rastvorljivosti polimera u vodi u širokom opsegu pH i povećanja kapaciteta za inkapsulaciju lekovitih supstanci tako dobijenih PEK, koji takođe predstavljaju obećavajuće nosače.