In this study, we report the synthesis of PDMAEMA-b-PCL-b-PDMAEMA via ATRP starting from two dibromide-end polycaprolactone (PCL) of 2 and 10 kDa. The copolymerization was confirmed by nuclear magnetic resonance and gel permeation chromatography. The micellar properties of copolymers with different compositions were studied at pH 5.0, 6.0, 7.0, and 7.5. According to results, properties such as critical micellar concentration (CMC), hydrophobicity of micelle cores, and particle size strongly depend on the length of PCL. The pH shows an important effect on the size of the colloidal aggregates. Micelles obtained from copolymers with the lowest polymerization degree of both segments showed to be more appropriate for the encapsulation of amphotericin B (AmB).

The clinical application of amphotericin B (AmB), a broad spectrum antifungal agent, is limited by its poor solubility in aqueous medium and also by its proven renal toxicity. In this work, AmB was encapsulated in micelles obtained from the self-assembly of PDMAEMA-b-PCL-b-PDMAEMA triblock copolymers. The amount of encapsulated AmB depended on the copolymer composition, and short blocks of polycaprolactone (PCL) and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) showed better performance. All the studied formulations exhibited a controlled release of AmB along 150 h. The formulations presented reduced hemotoxicity while maintaining antifungal activities against Candida albicans, Candida krusei, and Candida glabrata comparable with free AmB. A reduction on the hemotoxicity was found to be due to the slow release and subsequent low aggregation achieved with the use of polymer micelle nanocontainers.

A series of copolymers composed of methoxy poly(ethylene glycol) and a hydrophobic block of poly(ɛ‐caprolactone‐co‐propargyl carbonate) grafted with poly(2‐[dimethylamino]ethyl methacrylate) was synthesized by combining ring opening polymerization, azide‐alkyne click reaction, and atom transfer radical polymerization (ATRP). Well‐defined copolymers with a target composition and a tailored structure were achieved via the grafting from approach by using a single catalytic system for both click reaction and ATRP. Kinetic studies demonstrated the controlled/living character of the employed polymerization methods. The thermal properties and self‐assembly in aqueous medium of the graft copolymers were dependent on their composition. The resulting polymeric materials showed low cytotoxicity toward L929 cells, demonstrating their potential for biomedical applications. This type of materials containing cationic side chains tethered to biocompatible and biodegradable segments could be the basis for promising candidates as drug and gene delivery systems.

Poly(ethyleneimine) (PEI) is one of the most widely used cationic polymers for gene delivery. The high molecular weight polymer, which is commercially available, is highly efficient but also very cytotoxic. The reduction in charge density by using nonlinear architectures based on low molecular weight (LMW) PEI is a promising approach to produce safer DNA-vectors. Herein, a group of cationic graft copolymers with different composition containing a hydrophobic biocompatible backbone and LMW linear PEI (lPEI) grafts obtained by ring opening polymerization and click chemistry was studied. The self-assembly and DNA complexation behavior of these materials was analyzed by the gel retardation assay, zeta potential measurements, and dynamic light scattering. The copolymers formed positively charged particles in water with average sizes between 270 and 377 nm. After they were added to DNA in serum-free medium, these particles acquired negative/near-neutral charges and increased in size depending on the N/P ratio. All copolymers showed reduced cytotoxicity compared to the 25 kDa lPEI used as reference, but the transfection efficiency was reduced. This result suggested that the cationic segments were too small to fully condense the DNA and promote cellular uptake, even with the use of several grafts and the introduction of hydrophobic domains. The trends found in this research showed that a higher degree of hydrophobicity and a higher grafting density can enhance the interaction between the copolymers and DNA. These trends could direct further structural modifications in the search for effective and safe vectors based on this polycation.

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