Polysaccharide colloidal particles as delivery systems for macromolecules

Mucosal delivery of complex molecules such as peptides, proteins, oligonucl eotides, and plasmids is one of the most intensively studied subjects. The use of colloidal carriers made of hydrophilic polysaccharides, i.e. chitosa n, has arisen as a promising alternative for improving the transport of suc h macromolecules across biological surfaces. This article reviews the appro aches which have aimed to associate macromolecules to chitosan in the form of colloidal structures and analyzes the evidence of their efficacy in impr oving the transport of the associated molecule through mucosae and epitheli a. Chitosan has been shown to form colloidal particles and entrap macromole cules through a number of mechanisms, including ionic crosslinking, desolva tion, or ionic complexation, though some of these systems have been realize d only in conjunction with DNA molecules. An alternative involving the chem ical modification of chitosan has also been useful for the association of m acromolecules to self-assemblies and vesicles. To date, the in vivo efficac y of these chitosan-based colloidal carriers has been reported for two diff erent applications: while DNA-chitosan hybrid nanospheres were found to be acceptable transfection carriers, ionically crosslinked chitosan nanopartic les appeared to be efficient vehicles for the transport of peptides across the nasal mucosa. The potential applications and future prospects of these new systems fur mucosal delivery of macromolecules are highlighted at the e nd of the chapter. (C) 2001 Elsevier Science B.V. All rights reserved.