Methods for Synthesizing the Macromolecular Components of Smart Nanosized Carriers for Controlled Drug Delivery.


Paul Cătălin Balaure, Alexandru Mihai Grumezescu*: Methods for Synthesizing the Macromolecular Components of Smart Nanosized Carriers for Controlled Drug Delivery, Current Medicinal Chemistry, accepted, 2014.


Smart multifunctional polymeric nanocarriers responding to physicochemical changes in their environment or to external stimuli represent a new paradigm in the field of pharmaceutical formulations for controlled drug delivery. The introductory part of the present review concerns with this new concept and presents the main advantages resulting from the use of such nanovehicles instead of conventional much larger drug delivery systems. The access to drug nanocarriers based on smart supramolecular polymeric materials is primarily limited by the available polymerization methods capable to produce polymers with low polydispersity index as well as much more complex macromolecular architectures with strictly controlled chemical composition such as block copolymers and star or graft polymers or copolymers. This article reviews the state-of-the art in controlled/”living” free radical polymerization techniques as well as ring opening polymerization methods. Nitroxide mediated free radical polymerization (NMP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain-transfer polymerization (RAFT), single electron transfer-living radical polymerization (SET-LRP), single electron transfer-nitroxide radical coupling reaction (SET-NRC), cationic ring opening polymerization (CROP), anionic ring opening polymerization (AROP), and metal catalyzed ring opening polymerization are described highlighting their mechanistic details and their synthetic potential as well as their limitations. The description of each synthetic method is accompanied by illustrative examples of its applications in the field of drug nanocarriers. The final part of the article is dedicated to a special type of unimolecular, monodisperse nanocarriers, the dendrimers. Both divergent and convergent approaches to dendrimer synthesis are described along with a nice therapeutic application which takes advantage of the unique branched tree-like globular structure of dendrimers to treat cancer.