Application of Polymeric Micelles for Drug and Gene Delivery

Polymeric micelles have been extensively studied because of their ability to transfer biologically active agents, such as drugs and nucleic acids [...

Thermoresponsive Polyoxazolines as Vectors for Transfection of Nucleic Acids

Poly(2-oxazoline)s (POx) are an attractive platform for the development of non-viral gene delivery systems. The combination of POx moieties, exhibiting excellent biocompatibility, with DNA-binding polyethyleneimine (PEI) moieties into a single copolymer chain is a promising approach to balance toxicity and transfection efficiency. The versatility of POx in terms of type of substituent, copolymer composition, degree of polymerization, degree of hydrolysis, and chain architecture, as well as the introduction of stimuli-responsive properties, provides opportunities to finely tune the copolymer characteristics and physicochemical properties of the polyplexes to increase the biological performance. An overview of the current state of research in the POx–PEI-based gene delivery systems focusing particularly on thermosensitive POx is presented in this paper

Stabilized amphiphilic poly(styrene-co-diene)-b-poly(ethylene oxide) aggregates

-isoprene (I) or butadiene (B)) prepolymers (bearing hydroxyl or benzyl bromide end groups) and ethylene oxide or mono-methyl poly(ethylene glycol) (PEGs) were used to prepare a series of PS-co-PD-b-PEO amphiphilic copolymers. Investigations on the association and self-assembly of copolymers in dilute organic and in mixed organic/water solutions have been carried out both by light scattering and microscopic measurements. Nanosized and microsized species have been observed. Their shape depends on the hydrophobic/hydrophilic blocks ratio as well as on the solvent composition. Attempts on stabilizing the morphology of the aggregates/micelles have been made by UV-induced cross-linking of diene entities. It has been found that in some experiments, the stabilization proceeds throughout morphological rearrangement determined by the solvent nature and by the cross-linking protocol

Poly(vinyl benzyl trimethylammonium chloride) Homo and Block Copolymers Complexation with DNA

In this work we focus on the use of novel homo and block copolymers based on poly­(vinyl benzyl trimethyl­ammonium chloride) as gene delivery vectors. The homopolymers and block copolymers were synthesized by RAFT polymerization schemes and molecularly characterized. DNA/polymer complexes (polyplexes) in a wide range of N/P (amino-to-phosphate groups) ratios were prepared. The ability of the novel polymers to form complexes with linear DNA was investigated by light scattering, zeta potential, and ethidium bromide fluorescence quenching measurements. The resulting polyplexes were in the size range of 80–300 nm and their surface potential changed from negative to positive depending on the N/P ratio. The stability of polyplexes was monitored by changes in their hydrodynamic parameters in the presence of salt. The novel vector systems were visualized by transmission electron microscopy. The influence of factors such as molar mass, content, and chemical structure of the polycationic moieties as well as presence of a hydrophilic poly­[oligo­(ethylene glycol) methacrylate] block on the structure and stability of the polyplexes, kinetics of their formation, and effectiveness of the (co)­polymers to shrink and pack DNA was discussed

Synthesis of poly(styrene-co-diene)-block-polyglycidol. Self-association and stabilization of aggregates

A series of amphiphilic poly(styrene(S)-co-diene(D))-b-polyglycidol(G) block copolymers have been synthesized from a parent hydrophobic PS block. The block has been previously functionalized with double bonds of randomly distributed diene units (isoprene (I) or butadiene (B)). Hydrophilic PG blocks of different lengths have been introduced into the above prepolymers. Polymer aggregates of different size and shape have been obtained by dissolving the copolymers in organic and mixed organic/water solutions. The formation of nano-and microsized particles has been revealed by light scattering and microscopic studies. A protocol for preparation of aggregates of a tailored core/shell structure has been demonstrated. Stabilization of particles of the desired morphology with ongoing participation of double bonds in the diene units has been achieved by irradiation with UV light directly in solution

Influence of DNA Type on the Physicochemical and Biological Properties of Polyplexes Based on Star Polymers Bearing Different Amino Functionalities

The interactions of two star polymers based on poly (2-(dimethylamino)ethyl methacrylate) with different types of nucleic acids are investigated. The star polymers differ only in their functionality to bear protonable amino or permanently charged quaternary ammonium groups, while DNAs of different molar masses, lengths and topologies are used. The main physicochemical parameters of the resulting polyplexes are determined. The influence of the polymer’ functionality and length and topology of the DNA on the structure and properties of the polyelectrolyte complexes is established. The quaternized polymer is characterized by a high binding affinity to DNA and formed strongly positively charged, compact and tight polyplexes. The parent, non-quaternized polymer exhibits an enhanced buffering capacity and weakened polymer/DNA interactions, particularly upon the addition of NaCl, resulting in the formation of less compact and tight polyplexes. The cytotoxic evaluation of the systems indicates that they are sparing with respect to the cell lines studied including osteosarcoma, osteoblast and human adipose-derived mesenchymal stem cells and exhibit good biocompatibility. Transfection experiments reveal that the non-quaternized polymer is effective at transferring DNA into cells, which is attributed to its high buffering capacity, facilitating the endo-lysosomal escape of the polyplex, the loose structure of the latter one and weakened polymer/DNA interactions, benefitting the DNA release

Ciprofloxacin-Loaded Mixed Polymeric Micelles as Antibiofilm Agents

In this work, mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA29-b-PCL70-b-PDMAEMA29) and a non-ionic poly(ethylene oxide)–b-poly(propylene oxide)–b-poly(ethylene oxide) (PEO99-b-PPO67-b-PEO99) triblock copolymers, blended at different molar ratios, were developed. The key physicochemical parameters of MPMs, including size, size distribution, and critical micellar concentration (CMC), were evaluated. The resulting MPMs are nanoscopic with a hydrodynamic diameter of around 35 nm, and the ζ-potential and CMC values strongly depend on the MPM’s composition. Ciprofloxacin (CF) was solubilized by the micelles via hydrophobic interaction with the micellar core and electrostatic interaction between the polycationic blocks, and the drug localized it, to some extent, in the micellar corona. The effect of a polymer-to-drug mass ratio on the drug-loading content (DLC) and encapsulation efficiency (EE) of MPMs was assessed. MPMs prepared at a polymer-to-drug mass ratio of 10:1 exhibited very high EE and a prolonged release profile. All micellar systems demonstrated their capability to detach pre-formed Gram-positive and Gram-negative bacterial biofilms and significantly reduced their biomass. The metabolic activity of the biofilm was strongly suppressed by the CF-loaded MPMs indicating the successful drug delivery and release. The cytotoxicity of empty and CF-loaded MPMs was evaluated. The test reveals composition-dependent cell viability without cell destruction or morphological signs of cell death

Characterization of polymer vector systems based on partially hydrolyzed polyoxazoline for gene transfection

In this work, partially hydrolyzed thermoresponsive polyoxazoline was used for complexation with DNA. The resulting polyelectrolyte complex particles were characterized by dynamic and electrophoretic light scattering. They showed narrow size distribution and hydrodynamic diameter of 183 +/- 5 nm at 65 degrees C. To improve stability of the system at physiological temperature, the particles were coated with cross-linked polymer shell on their surface. A cytotoxicity study indicated lower toxicity of the investigated systems compared to the referent polyethylenimine. In addition, the transfection ability of the resulting vector systems was evaluated by flow cytometry. Transfection efficiencies up to 65 % that of the referent polyethylenimine indicated the potential of the vectors for DNA delivery

An Overview of Biofilm-Associated Infections and the Role of Phytochemicals and Nanomaterials in Their Control and Prevention

Biofilm formation is considered one of the primary virulence mechanisms in Gram-positive and Gram-negative pathogenic species, particularly those responsible for chronic infections and promoting bacterial survival within the host. In recent years, there has been a growing interest in discovering new compounds capable of inhibiting biofilm formation. This is considered a promising antivirulence strategy that could potentially overcome antibiotic resistance issues. Effective antibiofilm agents should possess distinctive properties. They should be structurally unique, enable easy entry into cells, influence quorum sensing signaling, and synergize with other antibacterial agents. Many of these properties are found in both natural systems that are isolated from plants and in synthetic systems like nanoparticles and nanocomposites. In this review, we discuss the clinical nature of biofilm-associated infections and some of the mechanisms associated with their antibiotic tolerance. We focus on the advantages and efficacy of various natural and synthetic compounds as a new therapeutic approach to control bacterial biofilms and address multidrug resistance in bacteria