11 research outputs found
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
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 polyÂ(vinyl benzyl trimethylÂammonium 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 polyÂ[oligoÂ(ethylene
glycol) methacrylate] block on the structure and stability of the
polyplexes, kinetics of their formation, and effectiveness of the
(co)Âpolymers to shrink and pack DNA was discussed
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
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
Partially hydrolyzed poly(n-propyl-2-oxazoline) : synthesis, aqueous solution properties, and preparation of gene delivery systems
Random copolymers of n-propyl-2-oxazoline and ethylenimine (PPrOx-PEI) were prepared by partial acidic hydrolysis of poly(n-propyl-2-oxazoline) (PPrOx). Dynamic and electrophoretic light scattering and diffusion ordered NMR spectroscopy were utilized to investigate aqueous solution properties of the copolymers. Above a specific cloud point temperature, well-defined nanoparticles were formed. The latter consisted of a core composed predominantly of PPrOx and a thin positively charged shell from PEI moieties that mediated formation of polyplexes with DNA. The polyplexes were prepared at 65 degrees C at varying N/P (amine-to-phosphate groups) ratios. They underwent structural changes upon temperature variations 65-25-37 degrees C depending on N/P. At N/P = 2 resulting in large swollen microgel particles were overcome by coating of the polyplex particles with a cross-linked polymeric shell. The shell retained the colloidal stability and preserved the physicochemical parameters of the initial polyplex particles while it reduced the high surface potential values. Progressive loss of cytotoxicity upon complexation with DNA and coating of polyplex particles was displayed
Smart Polymeric Nanocarriers of Met-enkephalin
This study describes a novel approach
to polymeric nanocarriers
of the therapeutic peptide met-enkephalin based on the aggregation
of thermoresponsive polymers. Thermoresponsive bioconjugate polyÂ((diÂ(ethylene
glycol) monomethyl ether methacrylate)-<i>ran</i>-(oligoÂ(ethylene
glycol) monomethyl ether methacrylate) is synthesized by AGET ATRP
using modified met-enkephalin as a macroinitiator. The abrupt heating
of bioconjugate water solution leads to the self-assembly of bioconjugate
chains and the formation of mesoglobules of controlled sizes. Mesoglobules
formed by bioconjugates are stabilized by coating with cross-linked
two-layer shell via nucleated radical polymerization of <i>N</i>-isopropylacrylamide using a degradable cross-linker. The targeting
peptide RGD, containing the fluorescence marker carboxyfluorescein,
is linked to a nanocarrier during the formation of the outer shell
layer. In the presence of glutathione, the whole shell is completely
degradable and the met-enkephalin conjugate is released. It is anticipated
that precisely engineered nanoparticles protecting their cargo will
emerge as the next-generation platform for cancer therapy and many
other biomedical applications
Partially Hydrolyzed Poly(<i>n</i>‑propyl-2-oxazoline): Synthesis, Aqueous Solution Properties, and Preparation of Gene Delivery Systems
Random copolymers of <i>n</i>-propyl-2-oxazoline and
ethylenimine (PPrOx–PEI) were prepared by partial acidic hydrolysis
of polyÂ(<i>n</i>-propyl-2-oxazoline) (PPrOx). Dynamic and
electrophoretic light scattering and diffusion-ordered NMR spectroscopy
were utilized to investigate aqueous solution properties of the copolymers.
Above a specific cloud point temperature, well-defined nanoparticles
were formed. The latter consisted of a core composed predominantly
of PPrOx and a thin positively charged shell from PEI moieties that
mediated formation of polyplexes with DNA. The polyplexes were prepared
at 65 °C at varying N/P (amine-to-phosphate groups) ratios. They
underwent structural changes upon temperature variations 65–25–37
°C depending on N/P. At N/P < 2, the polyplex particles underwent
minor changes because of formation of a surface layer of DNA that
acted as a barrier and prevented swelling and disintegration of the
initial particles. Dramatic rearrangements at N/P ≥ 2 resulting
in large swollen microgel particles were overcome by coating of the
polyplex particles with a cross-linked polymeric shell. The shell
retained the colloidal stability and preserved the physicochemical
parameters of the initial polyplex particles while it reduced the
high surface potential values. Progressive loss of cytotoxicity upon
complexation with DNA and coating of polyplex particles was displayed