1 Chitosan Based Self - assembled Nanoparticles in 2 Drug Delivery 3

Chitosan is a cationic polysaccharide usually obtained by alkaline deacetylation of chitin 13 poly(N-acetylglucosamine). It is biocompatible, biodegradable, mucoadhesive and non-toxic. These 14 excellent biological properties make chitosan a good candidate as platform for developing drug 15 delivery systems with improved biodistribution, increased specificity and sensitivity, and reduced 16 pharmacological toxicity. In particular, chitosan nanoparticles have been found appropriate for non17 invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications 18 are facilitated by the absorption-enhancing effect of chitosan. Many different procedures have been 19 proposed for obtaining chitosan nanoparticles. Particularly, the introduction of hydrophobic 20 moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance 21 promoting self-assembling is a current and appealing approach. The grafting agent can be a 22 hydrophobic moiety to form micelles that can entrap lipophilic drugs or it can be the drug itself. 23 Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of 24 polyelectrolyte complexes with polyanions. This paper reviews the main approaches developed for 25 preparing chitosan nanoparticles by self-assembling by both procedures and illustrates the state of 26 the art of their application in drug delivery. 27