In Situ Gelling Hydroxypropyl Cellulose Formulation Comprising Cannabidiol-Loaded Block Copolymer Micelles for Sustained Drug Delivery.

Cannabidiol (CBD) is a natural terpenophenolic compound with known pharmacological activities, but the poor solubility of CBD in water limits its widespread use in medicine and pharmacy. Polymeric (nano)carriers demonstrated high potential for enhancing the solubility and therapeutic activity of lipophilic drugs such as CBD. Here, we report the elaboration of a novel hydroxypropyl cellulose (HPC)-based in situ gelling formulation for controlled delivery of CBD. In the first stage, nanosized polymeric micelles from poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) (PEO-b-P(CyCL-co-CL) diblock copolymers) were used to increase the solubility of CBD in water. Different copolymers were assessed, and the carrier with the highest encapsulation efficiency (EE) and drug loading capacity (DLC) was selected for further elaboration of nanocomposite in situ gel formulations. Next, the sol-to-gel transition behavior of HPC as a function of K2SO4 concentration in the aqueous solution was investigated by microcalorimetry and dynamic oscillatory rheology, and the optimal formulation capable of forming a physical gel under physiological conditions was determined. Finally, injectable nanocomposite hydrogels comprising cannabidiol were fabricated, and their drug release profile and cytotoxicity against human tumor cell lines were evaluated. The in situ gels exhibited prolonged drug release over 12 h, controlled by gel erosion, and the cytotoxicity of formulated cannabidiol was comparable with that of a free drug.

Biorenewable Oxypropylated Pentane-1,2,5-triol as a Source for Incorporation in Rigid Polyurethane Foams.

In this study, as a product from the efficient Achmatowicz rearrangement and mild subsequent hydrogenation-reduction reactions of biorenewable C5 alcohols derived from lignocellulose, pentane-1,2,5-triol was successfully used after oxypropylation in the preparation of rigid polyurethane foams-one of the most important classes of polymeric materials. Despite the broad range of applications, the production of polyurethanes is still highly dependent on petrochemical materials considering the need of renewable raw materials and new process technologies for the production of polyol or isocyanate components as a key point for the sustainable development of polyurethane foams. The synthesized oxypropylated pentane-1,2,5-triol was analyzed using proton NMR spectroscopy, hydroxyl number, and viscosity, whereas the newly obtained foams incorporated with up to 30% biorenewable polyol were characterized using compressive stress, thermogravimetry, dynamic mechanical analysis, and scanning electron microscopy. The modified rigid polyurethanes showed better compressive strength (>400.0 kPa), a comparable thermal degradation range at 325-450 °C, and similar morphological properties to those of commercial polyurethane formulations.

Green Synthesis and the Evaluation of a Functional Amphiphilic Block Copolymer as a Micellar Curcumin Delivery System.

Polymer micelles represent one of the most attractive drug delivery systems due to their design flexibility based on a variety of macromolecular synthetic methods. The environmentally safe chemistry in which the use or generation of hazardous materials is minimized has an increasing impact on polymer-based drug delivery nanosystems. In this work, a solvent-free green synthetic procedure was applied for the preparation of an amphiphilic diblock copolymer consisting of biodegradable hydrophobic poly(acetylene-functional carbonate) and biocompatible hydrophilic polyethylene glycol (PEG) blocks. The cyclic functional carbonate monomer 5-methyl-5-propargyloxycarbonyl-1,3-dioxane-2-one (MPC) was polymerized in bulk using methoxy PEG-5K as a macroinitiator by applying the metal-free organocatalyzed controlled ring-opening polymerization at a relatively low temperature of 60 °C. The functional amphiphilic block copolymer self-associated in aqueous media into stable micelles with an average diameter of 44 nm. The copolymer micelles were physico-chemically characterized and loaded with the plant-derived anticancer drug curcumin. Preliminary in vitro evaluations indicate that the functional copolymer micelles are non-toxic and promising candidates for further investigation as nanocarriers for biomedical applications.

Novel Electrospun Composite Membranes Based on Polyhydroxybutyrate and Poly(vinyl formate) Loaded with Protonated Montmorillonite for Organic Dye Removal: Kinetic and Isotherm Studies.

The use of biodegradable polyesters derived from green sources and their combination with natural abundantly layered aluminosilicate clay, e.g., natural montmorillonite, meets the requirements for the development of new sustainable, disposable, and biodegradable organic dye sorbent materials. In this regard, novel electrospun composite fibers, based on poly ß-hydroxybutyrate (PHB) and in situ synthesized poly(vinyl formate) (PVF), loaded with protonated montmorillonite (MMT-H) were prepared via electrospinning in the presence of formic acid, a volatile solvent for polymers and a protonating agent for the pristine MMT-Na. The morphology and structure of electrospun composite fibers were investigated through SEM, TEM, AFM, FT-IR, and XRD analyses. The contact angle (CA) measurements showed increased hydrophilicity of the composite fibers incorporated with MMT-H. The electrospun fibrous mats were evaluated as membranes for removing cationic (methylene blue) and anionic (Congo red) dyes. PHB/MMT 20% and PVF/MMT 30% showed significant performance in dye removal compared with the other matrices. PHB/MMT 20% was the best electrospun mat for adsorbing Congo red. The PVF/MMT 30% fibrous membrane exhibited the optimum activity for the adsorption of methylene blue and Congo red dyes.

Correction: Grancharov et al. Flexible Polymer-Organic Solar Cells Based on P3HT:PCBM Bulk Heterojunction Active Layer Constructed under Environmental Conditions. Molecules 2021, 26, 6890.

The authors would like to correct a mistake in Figure 3 as published in the original publication [...].

Micellar Form of a Ferrocene-Containing Camphor Sulfonamide with Improved Aqueous Solubility and Tumor Curing Potential.

The discovery of new anticancer drugs with а higher, more specific activity and diminished side effects than the conventional chemotherapeutic agents is a tremendous challenge to contemporary medical research and development. To achieve a pronounced efficacy, the design of antitumor agents can combine various biologically active subunits in one molecule, which can affect different regulatory pathways in cancer cells. We recently demonstrated that a newly synthesized organometallic compound, a ferrocene-containing camphor sulfonamide (DK164), possesses promising antiproliferative activity against breast and lung cancer cells. However, it still encounters the problem of solubility in biological fluids. In this work, we describe a novel micellar form of DK164 with significantly improved solubility in aqueous medium. DK164 was embedded in biodegradable micelles based on a poly(ethylene oxide)-b-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone)-b-poly(ethylene oxide) triblock copolymer (PEO113-b-P(CyCL3-co-CL46)-b-PEO113), and the physicochemical parameters (size, size distribution, zeta potential, encapsulation efficiency) and biological activity of the obtained system were studied. We used cytotoxicity assays and flow cytometry to determine the type of cell death, as well as immunocytochemistry to assess the influence of the encapsulated drug on the dynamics of cellular key proteins (p53 and NFkB) and the process of autophagy. According to our results, the micellar form of the organometallic ferrocene derivate (DK164-NP) exhibited several advantages compared to the free substance, such as higher metabolic stability, better cellular uptake, improved bioavailability, and long-term activity, maintaining nearly the same biological activity and anticancer properties of the drug.

Redox-Responsive Crosslinked Mixed Micelles for Controllable Release of Caffeic Acid Phenethyl Ester.

We report the elaboration of redox-responsive functional micellar nanocarriers designed for triggered release of caffeic acid phenethyl ester (CAPE) in cancer therapy. Three-layered micelles, comprising a poly(ε-caprolactone) (PCL) core, a middle poly(acrylic acid)/poly(ethylene oxide) (PAA/PEO) layer and a PEO outer corona, were prepared by co-assembly of PEO113-b-PCL35-b-PEO113 and PAA13-b-PCL35-b-PAA13 amphiphilic triblock copolymers in aqueous media. The preformed micelles were loaded with CAPE via hydrophobic interactions between the drug molecules and PCL core, and subsequently crosslinked by reaction of carboxyl groups from PAA and a disulfide crosslinking agent. The reaction of crosslinking took place in the middle layer of the nanocarriers without changing the encapsulation efficiency (EE~90%) of the system. The crosslinked polymeric micelles (CPMs) exhibited superior structural stability and did not release CAPE in phosphate buffer (pH 7.4). However, in weak acidic media and in the presence of 10 mM reducing agent (dithiothreitol, DTT), the payload was released at a high rate from CPMs due to the breakup of disulfide linkages. The physicochemical properties of the nanocarriers were investigated by dynamic and electrophoretic light scattering (DLS and ELS) and atomic force microscopy (AFM). The rapid release of CAPE under intracellular-like conditions and the lack of premature drug release in media resembling the blood stream (neutral pH) make the developed CPMs a promising candidate for controllable drug release in the microenvironment of tumors.

Flexible Polymer-Organic Solar Cells Based on P3HT:PCBM Bulk Heterojunction Active Layer Constructed under Environmental Conditions.

In this study, some crucial parameters were determined of flexible polymer-organic 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 elements' 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 (I-V) measurements, quantum efficiency, impedance spectroscopy, surface morphology, and time-degradation experiments. The control over morphology of active layer thin film was achieved by post-deposition thermal treatment at temperatures of 110-120 °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. Polymer-organic solar cells prepared on plastic substrates showed comparable current-voltage characteristics and structural properties but need further device stability improvement according to traditionally constructed cells on glass substrates.

Superior proapoptotic activity of curcumin-loaded mixed block copolymer micelles with mitochondrial targeting properties.

Targeting tumor cell mitochondria is a prospective strategy for highly effective anticancer therapy. Consequently, the development of potent systems for the targeted delivery of mitochondria-acting therapeutics to mitochondria has the potential to boost this sector of nanomedicine. In this study, a functional mixed micellar system based on two co-assembled triblock copolymers, poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) bearing triphenylphosphonium ligands (PDMAEMA(TPP+)20-b-PCL70-b-PDMAEMA(TPP+)20) and poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO113-b-PCL70-b-PEO113), was assessed for the mitochondria targeted delivery of curcumin. The high proapoptotic activity of the system and the sub-cellular mechanisms of cytotoxicity were demonstrated using a chemosensitive HL-60 cell line and its resistant alternative HL-60/DOX. Next, the successful localization of nanocarriers in mitochondria was proved by fluorescence microscopy with the aid of DAPI (4',6-diamidino-2-phenylindole) as a cellular localization tracker. The in vitro experiments revealed the great potential of the functional system developed for the targeted delivery of curcumin to mitochondria, causing programmed tumor cell death.

Individually addressable recessed gold microelectrode arrays with monolayers of thio-cyclodextrin nanocavities.

Four, individually addressable 30 microm diameter, e-beam deposited, gold microelectrodes recessed by 6 microm were suitably spaced on a single substrate to avoid diffusional overlap between each microelectrode. The single substrate device was functionalised with thiolated alpha-, beta-, and gamma-cyclodextrin nanocavities without spacer groups to ensure close proximity of the cavities to the electrode surface. The microelectrodes were assessed in two stages. The e-beam deposited micron sized electrodes were characterized using models for recessed and inlaid microdisk electrodes. Subsequently, each individually addressable, atomically flat, micro-patterned gold electrode with thiolated CD ensembles was treated as a nanoporous electrode assembly. Theoretical and experimental results were compared using cyclic voltammetry. Atomic force microscopy was also used to characterise the modified microelectrodes. Comparisons were made with thiolated CDs deposited on macroelectrodes. This is the first report of the behaviour of immobilized CD nanocavities ensembles on atomically flat gold microelectrodes.