11 research outputs found
Insulin/Poly(ethylene glycol)-block-poly(L-lysine) Complexes: Physicochemical Properties and Protein Encapsulation
Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a neutral-cationic block polyelectrolyte). These macromolecules can encapsulate INS molecules in aqueous conditions via electrostatic interactions. Light scattering techniques are used in order to examine the complexation process of the hybrid nanoparticles in a gamut of buffers, as a function of protein concnetration. The physicochemical and structural characteristics of the complexes depend on the ionic strength of the aqueous medium, while the concentration of PEG-b-PLys was constant through the series of solutions. As INS concentration increased each polyelectrolyte chain interacts with an increasing number of INS molecules, the degree of charge neutralization becomes higher and the size distribution of the complexes decreased also, especially at the highest ionic strength. The size/structure of complexes diluted in biological medium indicated that the copolymer imparts stealth properties and colloidal and biological stability to the complexes, which could in turn affect the clearance properties in vivo. Therefore, these studies could be a rational roadmap for designing the optimum complexes/effective nanocarriers for proteins and peptides
Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation
Spherical nucleic acids (SNAs) have gained significant attention due to their unique properties allowing them to overcome the challenges that face current nanocarriers used for gene therapies. The aim of this study is to synthesize and characterize polymer–oligonucleotide conjugates of different architecture and to evaluate the possibility of forming SNAs with biodegradable cores. Initially, two types of azide (multi)functional polyester-based (co)polymers were successfully synthesized and characterized. In the next step, short oligonucleotide strands were attached to the polymer chains applying the highly efficient and metal-free “click” reaction, thus forming conjugates with block or graft architecture. Both conjugates spontaneously self-assembled in aqueous media forming nanosized SNAs with a biodegradable polyester core and a surface of oligonucleotide chains as evidenced from dynamic and electrophoretic light scattering measurements. The nano-assemblies were in vitro evaluated for potential cytotoxicity. Furthermore, the interactions of the newly synthesized SNAs with membrane lipids were studied. The preliminary results indicate that both types of polymer-based SNAs are good candidates for potential application in gene therapy and that it is worth to be further evaluated
Triblock Copolymer Micelles with Tunable Surface Charge as Drug Nanocarriers: Synthesis and Physico-Chemical Characterization
Polymeric micelles have gained increasing interest as efficient drug delivery systems for cancer treatment and diagnosis. The aim of the present study was to construct and to evaluate novel polymeric nanosized drug carriers with tunable surface charges. Initially, amphiphilic triblock copolymers with predetermined molar mass characteristics were synthesized by applying controlled polymerization techniques. The copolymers self-assembled in aqueous media into coreâshell spherical micelles, comprising a biodegradable hydrophobic poly(D,L-lactide) core, positively charged middle layer of poly((2-dimethylamino)ethyl methacrylate), and an outer shell of neutral hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate), with various densities of the short polyether side chains. The block copolymer micelles with average diameters of about 70 nm and surface charges varying from strongly positive to neutral were characterized and loaded with the model, natural, hydrophobic drug curcumin. Characteristics such as drug loading efficiency, in-vitro drug release profiles, and stability under physiological conditions were evaluated and discussed in terms of nanocarriersâ composition. As a result, the most promising candidates for potential application in nanomedicine were identified
Solvent-Free Synthesis of Multifunctional Block Copolymer and Formation of DNA and Drug Nanocarriers
The synthesis of well-defined multifunctional polymers is of great importance for the development of complex materials for biomedical applications. In the current work, novel and multi-amino-functional diblock copolymer for potential gene and drug delivery applications was successfully synthesized. A highly efficient one-step and quantitative modification of an alkyne-functional polycarbonate-based precursor was performed, yielding double hydrophilic block copolymer with densely grafted primary amine side groups. The obtained positively charged block copolymer co-associated with DNA, forming stable and biocompatible nanosized polyplexes. Furthermore, polyion complex (PIC) micelles with tunable surface charge and decorated with cell targeting moieties were obtained as a result of direct mixing in aqueous media of the multi-amino-functional block copolymer and a previously synthesized oppositely charged block copolymer bearing disaccharide end-group. The obtained well-defined nanosized PICâmicelles were loaded with the hydrophobic drug curcumin. Both types of nanoaggregates (polyplexes and PICâmicelles) were physico-chemically characterized. Moreover, initial in vitro evaluations were performed to assess the nanocarriersâ potential for biomedical applications
Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation
Spherical nucleic acids (SNAs) have gained significant attention due to their unique properties allowing them to overcome the challenges that face current nanocarriers used for gene therapies. The aim of this study is to synthesize and characterize polymerâoligonucleotide conjugates of different architecture and to evaluate the possibility of forming SNAs with biodegradable cores. Initially, two types of azide (multi)functional polyester-based (co)polymers were successfully synthesized and characterized. In the next step, short oligonucleotide strands were attached to the polymer chains applying the highly efficient and metal-free âclickâ reaction, thus forming conjugates with block or graft architecture. Both conjugates spontaneously self-assembled in aqueous media forming nanosized SNAs with a biodegradable polyester core and a surface of oligonucleotide chains as evidenced from dynamic and electrophoretic light scattering measurements. The nano-assemblies were in vitro evaluated for potential cytotoxicity. Furthermore, the interactions of the newly synthesized SNAs with membrane lipids were studied. The preliminary results indicate that both types of polymer-based SNAs are good candidates for potential application in gene therapy and that it is worth to be further evaluated
Insulin/poly(ethylene glycol)-<i>block</i>-poly(lâlysine) Complexes: Physicochemical Properties and Protein Encapsulation
Insulin
(INS) was encapsulated into complexes with polyÂ(ethylene
glycol)-<i>block</i>-polyÂ(l-lysine) <b>(</b>PEG-<i>b</i>-PLys), which is a polypeptide-based block
copolymer (a neutral-cationic block polyelectrolyte). The particular
cationic-neutral block copolymer can complex INS molecules in aqueous
media via electrostatic interactions. Light-scattering techniques
are used to study the complexation process and structure of the hybrid
nanoparticles in a series of buffers, as a function of protein concentration.
The physicochemical and structural characteristics of the complexes
depend on the ionic strength of the aqueous medium, while the concentration
of PEG-<i>b</i>-PLys was constant through the series of
solutions. As INS concentration increased the size distribution of
the complexes decreased, especially at the highest ionic strength.
The size/structure of complexes diluted in biological medium indicated
that the copolymer imparts stealth properties and colloidal and biological
stability to the complexes, features that could in turn affect the
clearance properties in vivo. Therefore, these studies could be a
rational roadmap for designing the optimum complexes/effective nanocarriers
for proteins and peptides
Flexible PolymerâOrganic Solar Cells Based on P3HT:PCBM Bulk Heterojunction Active Layer Constructed under Environmental Conditions
In this study, some crucial parameters were determined of flexible polymerâorganic solar cells prepared from an active layer blend of poly(3-hexylthiophene) (P3HT) and the fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) mixed in 1:1 mass ratio and deposited from chlorobenzene solution by spin-coating on poly(ethylene terephthalate) (PET)/ITO substrates. Additionally, the positive effect of an electron transport layer (ETL) prepared from zinc oxide nanoparticles (ZnO np) on flexible photovoltaic elementsâ performance and stability was investigated. Test devices with above normal architecture and silver back electrodes deposed by magnetron sputtering were constructed under environmental conditions. They were characterized by current-voltage (IâV) measurements, quantum efficiency, impedance spectroscopy, surface morphology, and timeâdegradation experiments. The control over morphology of active layer thin film was achieved by post-deposition thermal treatment at temperatures of 110â120 °C, which led to optimization of device morphology and electrical parameters. The impedance spectroscopy results of flexible photovoltaic elements were fitted using two R||CPE circuits in series. Polymerâorganic solar cells prepared on plastic substrates showed comparable currentâvoltage characteristics and structural properties but need further device stability improvement according to traditionally constructed cells on glass substrates
Chemical force microscopy of stimuli-responsive adhesive copolymers
Atomic force microscopy with chemically sensitive tips was used to investigate the hydrophobic and electrostatic interaction forces of a stimuli-responsive adhesive polymer, and their dynamic changes in response to water immersion and salt concentration. Block copolymer-filled coatings were obtained by incorporating an amphiphilic block copolymer containing a polydimethylsiloxane (PDMS) block and a poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) block in a PDMS matrix. Topographic images of fresh samples revealed the presence of nanoscale domains associated with the presence of copolymers,covered by a thin layer of PDMS. Prolonged (30 days) immersion in aqueous solution led to the exposure of the hydrophilic PDMAEMA chains on the surface. Using adhesion force mapping with hydrophobic tips, we showed that fresh samples were uniformly hydrophobic, while aged samples exhibited lower surface hydrophobicity and featured nanoscale hydrophilic copolymer domains. Force mapping with negatively charged tips revealed remarkable salt-dependent force plateau signatures reflecting desorption of polyelectrolyte copolymer chains. These nanoscale experiments show how solventinduced conformational changes of stimuli-responsive copolymers can be used to modulate surface adhesion
Recent Applications of Alkene Metathesis in Fine Chemical Synthesis
During the last decade or so, the emergence of the metathesis reaction in organic synthesis has revolutionised the strategies used for the construction of complex molecular structures. Olefin metathesis is indeed particularly suited for the construction of small open-chain molecules and macrocycles using crossmetathesis and ring-closing metathesis, respectively. These reactions serve, inter alia, as key steps in the synthesis of various agrochemicals and pharmaceuticals such as macrocyclic peptides, cyclic sulfonamides, novel macrolides, or insect pheromones. The present chapter is aiming at illustrating the great synthetic potential of metathesis reactions. Shortcomings, such as the control of olefin geometry and the unpredictable effect of substituents on the reacting olefins, will also be addressed. Examples to be presented include epothilones, amphidinolides, spirofungin A, and archazolid. Synthetic approaches involving silicon-tethered ring-closing metathesis, relay ring-closing metathesis, sequential reactions, domino as well as tandem metathesis reactions will also be illustrated
Modification of the Adhesive Properties of Silicone-Based Coatings by Block Copolymers
The improvement of the (bio)Âadhesive
properties of elastomeric
polydimethylsiloxane (PDMS) coatings is reported. This is achieved
by a surface modification consisting of the incorporation of block
copolymers containing a PDMS block and a polyÂ(2-(dimethylamino)Âethyl
methacrylate) (PDMAEMA) block in a PDMS matrix, followed by matrix
cross-linking and immersion of the obtained materials in water. Contact
angle measurements (CA), X-ray photoelectron spectroscopy (XPS), and
atomic force microscopy (AFM) showed the presence of the PDMAEMA block
at the surface, drastic morphology changes, and improved adhesion
properties after immersion in water. Finally, underwater bioadhesion
tests show that mussels adhere only to block copolymer-filled coatings
and after immersion in water, i.e., when the PDMAEMA blocks have been
brought to the coating surface. These observations highlight the significant
role of hydrophilic groups in the surface modification of silicone
coatings