Chitosan is a naturally occurring polymer derived from the deacetylation of chitin, which is an abundant carbohydrate found mainly in the shells of various marine and terrestrial (micro)organisms. Chitosan has been extensively used to construct nanoparticles (NPs), which are biocompatible, biodegradable, non-toxic, easy to prepare, and can function as effective drug delivery systems. Moreover, chitosan NPs have been employed in gene and vaccine delivery, as well as advanced cancer therapy, and they can also serve as new therapeutic tools against viral infections. In this review, we summarize the most recent developments in the field of chitosan-based NPs intended as nucleic acid delivery vehicles and gene therapy vectors. Special attention is given to the technological aspects of chitosan complexes for nucleic acid delivery.

We report the synthesis, quaternization and self-assembly in aqueous media of novel amphiphilic and pH responsive triblock terpolymers of the type poly[2-(dimethylamino)ethyl methacrylate-b-lauryl methacrylate-b-(oligo ethylene glycol)methacrylate] (PDMAEMA-b-PLMA-b-POEGMA). The terpolymers were synthesized by RAFT polymerization and molecularly characterized by SEC, ¹H-NMR and FTIR spectroscopy. Methyl iodide was used for quaternization of the PDMAEMA blocks, in order to increase the solubility of the terpolymers in water and to impart a permanent positive charge, transforming them to amphiphilic block polyelectrolytes. PDMAEMA-b-PLMA-b-POEGMA and QPDMAEMA-b-PLMA-b-POEGMA terpolymers self-assemble into spherical micelles in aqueous media, as indicated by light scattering and scanning electron microscopy results. The dimensions of the micelles were not affected appreciably by changes in the pH of the solutions, an observation attributed to crowding within the mixed PDMAEMA/POEGMA corona. QPDMAEMA-b-PLMA-b-POEGMA terpolymer micelles were found to dissociate by an increase of ionic strength, due to the collapse of the QPDMAEMA blocks and as a result of the low T_g of the PLMA core block.

This review article aims to cover the most recent advances regarding the synthesis of linear ABC-type triblock terpolymers and star-shaped polymers by RAFT polymerization, as well as their self-assembly properties in aqueous solutions. RAFT polymerization has received extensive attention, as it is a versatile technique, compatible with a great variety of functional monomers and reaction conditions, while providing exceptional and precise control over the final structure, with well-defined side-groups and post-polymerization engineering potential. Linear triblock terpolymers synthesis can lead to very interesting novel ideas, since there are countless combinations of stimuli/non-stimuli and hydrophilic/hydrophobic monomers that someone can use. One of their most interesting features is their ubiquitous ability to self-assemble in different nanostructures depending on their degree of polymerization (DP), block composition, solubilization protocol, internal and external stimuli. On the other hand, star-shaped polymers exhibit a more stable nanostructure, with a distinct crosslinked core and arm blocks that can also incorporate stimuli-responsive blocks for “smart” applications.

This review aims to highlight the most recent advances in the field of the synthesis of branched copolymers and nanogels using reversible addition-fragmentation chain transfer (RAFT) polymerization. RAFT polymerization is a reversible deactivation radical polymerization technique (RDRP) that has gained tremendous attention due to its versatility, compatibility with a plethora of functional monomers, and mild polymerization conditions. These parameters lead to final polymers with good control over the molar mass and narrow molar mass distributions. Branched polymers can be defined as the incorporation of secondary polymer chains to a primary backbone, resulting in a wide range of complex macromolecular architectures, like star-shaped, graft, and hyperbranched polymers and nanogels. These subcategories will be discussed in detail in this review in terms of synthesis routes and properties, mainly in solutions.

Herein, poly[quaternized 2-(dimethylamino)ethyl methacrylate-b-lauryl methacrylate-b-(oligo ethylene glycol)methacrylate] (QPDMAEMA-b-PLMA-b-POEGMA) cationic amphiphilic triblock terpolymers were used as vehicles for the complexation/encapsulation of insulin (INS). The terpolymers self-assemble in spherical micelles with PLMA cores and mixed QPDMAEMA/POEGMA coronas in aqueous solutions. The cationic micelles were complexed via electrostatic interactions with INS, which contains anionic charges at pH 7. The solutions were colloidally stable in all INS ratios used. Light-scattering techniques were used for investigation of the complexation ability and the size and surface charge of the terpolymer/INS complexes. The results showed that the size of the complexes increases as INS ratio increases, while at the same time the surface charge remains positive, indicating the formation of clusters of micelles/INS complexes in the solution. Fluorescence spectroscopy measurements revealed that the conformation of the protein is not affected after the complexation with the terpolymer micellar aggregates. It was observed that as the solution ionic strength increases, the size of the QPDMAEMA-b-PLMA-b-POEGMA/INS complexes initially decreases and then remains practically constant at higher ionic strength, indicating further aggregation of the complexes. atomic force microscopy (AFM) measurements showed the existence of both clusters and isolated nanoparticulate terpolymer/protein complexes.