Sulfobutylether-β-cyclodextrin/chitosan nano- and microparticles and their physicochemical characteristics

Metastable polymer/cyclodextrin nano- and microparticles (NPs) were prepared from low molecular weight chitosan (CS), Mw about 10 kDa, and sulfobutylether β-cyclodextrin (SBEβCD). CS is a cationic polysaccharide containing numerous protonated amino groups (pKa about 6.5). SBEβCD is a β-cyclodextrin derivative with six to seven negatively charged sulfobutyl ether groups per cyclodextrin molecule. Ionotropic gelation technique was used to prepare the NPs. The NP matrix was composed of low molecular weight cationic CS polysaccharide cross-linked with polyvalent anions (SBEβCD). The diameter of the NPs ranged from 200 to almost 1,000 nm and was controlled by the CS:SBEβCD molar ratio during NP preparation. Hydrocortisone (HC) is a lipophilic drug with limited aqueous solubility (0.3mg/ml). HC displayed AL-type phase-solubility diagrams in aqueous solutions containing either SBEβCD or CS, although CS had negligible solubilizing effect. The ability of the NPs to encapsulate HC decreased with increasing CS concentration during preparation of the NPs even though the SBEβCD content of the NPs increased with increasing CS concentration. This decrease in HC encapsulation was related to the concentration; the ionic crosslinking provides better encapsulation at low initial SBEβCD and CS concentrations.