Background: Chitosan structure versatility toward a change in an external stimulus represents a
“must have” for the pharmaceutical applications, especially for the pharmaceutical formulations. Chemical
modification can open new ways to obtain materials with tailored properties. Despite the great interest for conventional
graft modifications, controlled/living free radical polymerizations (i.e. RAFT, ATRP, etc.) and advanced
chemistry techniques (i.e. click chemistry) seem more attractive nowadays and involve facile and fast
procedure, high regioselectivity, quantitative yield, mild reaction conditions without generation of by-products.
Objective: The present review provides a detailed state of art of the chemical modification of chitosan i.e. tailored
side-chain functionalization using RAFT polymerization and click chemistry for specific applications
within pharmaceutical formulations taking into account the applicative aspect regarding the need of pharmaceuticals.
Conclusion: The review showed the routes of current approaches for side chain modification of chitosan including
graft, block copolymers or other structural variations. The esterification of RAFT agents on chitosan by
using carbonyl activating reagents enables producing chitosan graft and block copolymers with controlled architectures
while the development of protection/ deprotection chemistry of chitosan made possible the regioselective
modification of chitosan or other polysaccharides. Although these developments increased the potential
of chitosan, still the chemical functionality and architectural diversity of the derivatives are limited. Application
of modern techniques e.g. RAFT polymerization, “click” chemistry has opened new “doors” for the science
of controlled and chemoselective synthesis of well- tailored derivatives with unique and superior properties.