STIMULI-SENSITIVE PARTICLES FOR DRUG DELIVERY - Biologically-Responsive Hybrid Biomaterials - page 167

impede the achievement of equilibrium. A key advantage of the ATRP technique
is that the resulting polymer retains the halogen moiety in the growing chain end,
which allows reactivation of the chain end and use as a macroinitiator for a
second polymerization reaction. ATRP is typically used to synthesize higher
molecular weight polymers compared to the RAFT technique. One example is
the synthesis of PMMA (MW 180 kDa) by ATRP using sulfonyl chloride
initiator and copper as a catalyst yielding a polymer with a PDI of 1.1 compared
to a PDI of 1.5 when synthesized using random free radical polymerization. [48]
2.3. Nitroxide-mediated polymerization (NMP) technique
The rationale behind nitroxide-mediated polymerization is to use the nitroxide
group to efficiently cap the end of the growing polymer chains by a reversible
termination reaction to ensure equal growth of all polymer chains while
suppressing undesirable termination reactions. NMP reactions utilize
alkoxyamines to function as both an initiator and end-capping group, which
gives full control over the concentration of initiating radicals in the reaction
mixture. This polymerization reaction starts with hemolytic cleavage of the
alkoxyamine upon heating to produce the initiating radical (R3·) and the
stabilized (·ONR1R2) that should be present long enough for a monomer unit
(M) to react with the initiating radical before recombination takes place
(Figure 8). Originally, NMP reactions were carried out at elevated temperatures
(> 100°C), but have also been recently carried out in aqueous media at lower
temperatures (<100°C). [49] It is important to note that the alkoxyamine group
can withstand reaction conditions of other controlled radical polymerizations
such as RAFT and ATRP, which makes it possible to synthesize block co-
polymers by combining NMP with other techniques. [48]
Fig. 8. Mechanism of nitroxide-mediated polymerization (NMP) technique.