The influence of multivalent phosphate structure on the properties of ionically cross-linked chitosan films for controlled drug release.

The aim of this paper was to investigate the electrostatic interactions between multivalent phosphates (phosphate (Phos), pyrophosphate (Pyro) and tripolyphosphate (TPP)) and chitosan, as well as the influence of electrostatic interactions on the properties of chitosan films ionically cross-linked by the above mentioned phosphates. The charge number of Phos was too low to interact with chitosan, while Pyro and TPP with more negative charges showed a significant ability to ionically cross-link chitosan. Solution pH played an important role on the charge numbers carried by Pyro, TPP and chitosan, especially for Pyro/chitosan. For instance, at pH less than 2.0 the interaction between Pyro and chitosan disappeared, while for TPP/chitosan even in solutions at pH less than 0.5 it still existed. Media pH and ionic strength also had a significant influence on the properties of cross-linked chitosan film with multivalent phosphates. Usually these films swelled and drug was released quickly in acidic conditions (such as in simulated gastric fluid) while under neutral conditions (such as in simulated intestinal fluid) they remained in a shrinkage state and drug was released slowly. Compared to TPP/chitosan films, Pyro/chitosan films exhibited much better pH-sensitive swelling and controlled release properties due to their relatively weak electrostatic interaction. The same reasoning was used to explain the significant acceleration of Pyro/chitosan film swelling and model drug release observed on adding sodium chloride. These films may be promising for site-specific drug delivery in the stomach.