Preparation of well-defined brush-like block copolymers for gene delivery applications under biorelevant reaction conditions.

Well-defined oligo(ethylene glycol) methyl ether methacrylate (OEOMA) based block copolymers with cationic segments composed by N,N-(dimethylamino) ethyl methacrylate (DMAEMA) and/or 2-(diisopropylamino) ethyl methacrylate (DPA) were developed under biorelevant reaction conditions. These brush-type copolymers were synthesized through supplemental activator and reducing agent (SARA) atom transfer radical polymerization (ATRP) using sodium dithionite as SARA agent. The synthesis was carried out using an eco-friendly solvent mixture, very low copper catalyst concentration, and mild reaction conditions. The structure of the block copolymers was characterized by size exclusion chromatography (SEC) analysis and 1H nuclear magnetic resonance (NMR) spectroscopy. The pH-dependent protonation of these copolymers enables the efficient complexation with plasmid DNA (pDNA), yielding polyplexes with sizes ranging from 200 up to 700 nm, depending on the molecular weight of the copolymers, composition and concentration used. Agarose gel electrophoresis confirmed the successful pDNA encapsulation. No cytotoxicity effect was observed, even for N/P ratios higher than 50, for human fibroblasts and cervical cancer cell lines cells. The in vitro cellular uptake experiments demonstrated that the pDNA-loaded block copolymers were efficiently delivered into nucleus of cervical cancer cells. The polymerization approach, the unique structure of the block copolymers and the efficient DNA encapsulation presented can open new avenues for development of efficient tailor made gene delivery systems under biorelevant conditions.

Room temperature aqueous self-assembly of poly(ethylene glycol)-poly(4-vinyl pyridine) block copolymers: From spherical to worm-like micelles.

The solution self-assembly and the formation, at room temperature, of a wide range of nanostructures based on monomethyl ether poly(ethylene glycol)-b-poly(4-vinyl pyridine) (mPEG-b-P4VP) block copolymer is reported. Copolymers with different compositions and molecular weights were synthesized through Atom Transfer Radical Polymerization (ATRP) method. The solution self-assembly of the block copolymers was studied by transmission electron microscopy (TEM) for different solution pHs. It was found that the formation of non-spherical nanostructures, such as rod- and worm-like micelles can be easily achieved, at room temperature, by simply varying the molecular weight of the different segments as well as the mPEG to P4VP ratio in the block copolymer structure. Because P4VP segments are known to form strong complexes with metals, the nanostructures prepared in this manuscript can find innovative applications in the biomedical field and be used as nano-templates for inorganic materials.

Drug delivery systems: Advanced technologies potentially applicable in personalized treatments.

Advanced drug delivery systems (DDS) present indubitable benefits for drug administration. Over the past three decades, new approaches have been suggested for the development of novel carriers for drug delivery. In this review, we describe general concepts and emerging research in this field based on multidisciplinary approaches aimed at creating personalized treatment for a broad range of highly prevalent diseases (e.g., cancer and diabetes). This review is composed of two parts. The first part provides an overview on currently available drug delivery technologies including a brief history on the development of these systems and some of the research strategies applied. The second part provides information about the most advanced drug delivery devices using stimuli-responsive polymers. Their synthesis using controlled-living radical polymerization strategy is described. In a near future it is predictable the appearance of new effective tailor-made DDS, resulting from knowledge of different interdisciplinary sciences, in a perspective of creating personalized medical solutions.