Chitosan-based nanoparticles by ionotropic gelation

Ionotropic gelation between chitosan, as the polycation of acidic pH, and TPP (penta sodium triphosphate aka tripolyphosphate) as the anionic oligomeric partner leads to the formation of colloidal systems which can range from approximately 100nm to 2000nm. Depending on the conditions, particles with different properties can be obtained including differences in size, zeta potential, stability at different pH values or loading characteristics [Janes 2001 and therein mentioned literature, review article, Agnihotri 2004 and therein mentioned literature, review article]. Such nano-sized colloidal systems are of great interest as drug or active component delivery systems. The electrostatic interaction is particularly suited for the incorporation of biopharmaceuticals for two reasons: First, the formation process is solely based on the electrostatic interaction of oppositely charged polymers; hence, no chemical modification needs to be applied. Secondly, the incorporation can be achieved in aqueous, physiological conditions [Agnihotri 2004]. Incorporated biopharmaceuticals such as proteins or oligonucleotides may be protected against degradation in in vivo applications [Aktas 2005, Gan 2006]. Chitosan-TPP-nanoparticles are mainly characterized by a positive zeta potential. Interaction is therefore strong towards any negative surface charge, or negatively charged oligoanions and polyanions. This type of interaction can be used to obtain strong adhesion and immediate immobilisation on negatively charged surfaces e.g. mucosal tissue [Vila 2003]. On the other hand, interactions with anionic proteins and polymers may stimulate the aggregation or precipitation phenomena, limiting the applicability of some chitosan-TPP nanoparticle formulations. Recently presented studies outlined the stability of chitosan-TPP nanoparticles and particularly, the limitations of this particle stability using model body fluids [Gan 2006]. The work we expose in the present paper is a deeper investigation into the stability of this chitosan-TPP nanoparticle system.