Sustained drug release using supramolecular hydrogels composed of cyclodextrin inclusion complexes with PCL/PEG multiple block copolymers

Methadone hydrochloride is a narcotic drug used to relieve chronic pain and control withdrawal symptoms in people undergoing detoxification for opiate addiction, but poses some limits. To reduce the limits and increase the drug’s effectiveness, supramolecular hydrogels composed of α-CD (α-cyclodextrin) and PCL/PEG (polycaprolactone/polyethylene glycol) copolymers, which gained attention due to their advantages, were chosen in this study as controlled-release formulations. PCL/PEG/PCL and PCL/PEG copolymers were synthesized by a microwave-assisted method and then supramolecular hydrogels were prepared by mixing the solutions of copolymers/drug and α-CD to make a methadone hydrochloride sustained-release system. Effects of the drug, copolymer, and α-CD concentrations and copolymer structure on gelation time were also investigated. The systems had rheological properties that depended on copolymer construction and component concentrations. The microwave-assisted method provides an accelerated synthesis of the copolymers with yield of 57 % and low level of impurities. The supramolecular hydrogels demonstrated shear thinning and thixotropic behavior and regained their networks quickly after passing through a fine needle. Due to the porous construction of supramolecular hydrogels, they swell in the presence of fluids and absorb large quantities of water, thereby making the system comprehensively biocompatible. In this study, supramolecular hydrogels composed of α-CD with tri- and di-block copolymers were investigated and found to have rheological properties that depended on copolymer construction and component concentrations. Changing one parameter alone like copolymer or α-CD concentration or the length of blocks could not significantly affect on the drug release, but combination of these factors was efficient. Results of the present study indicated that supramolecular hydrogels composed of α-CD and PCL/PEG copolymers are appropriate drug delivery systems that can release methadone hydrochloride in a sustained manner.     

Photoluminescence study of SBA-15@ZnO/Au nanocomposite for potential use in Staphylococcus aureus detection

Journal of Porous Materials - Staphylococcus aureus is most common causes of hospital-acquired infections and food-associated disease. In the last years, sensing platform based on fluorescence-...     

Super Magnetic Niosomal Nanocarrier as a New Approach for Treatment of Breast Cancer: A Case Study on SK-BR-3 and MDA-MB-231 Cell Lines

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe₂O₄ core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe₂O₄@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe₂O₄@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.     

Extracellular Vesicles: Interplay with the Extracellular Matrix and Modulated Cell Responses

The discovery that cells secrete extracellular vesicles (EVs), which carry a variety of regulatory proteins, nucleic acids, and lipids, has shed light on the sophisticated manner by which cells can communicate and accordingly function. The bioactivity of EVs is not only defined by their internal content, but also through their surface associated molecules, and the linked downstream signaling effects they elicit in target cells. The extracellular matrix (ECM) contains signaling and structural molecules that are central to tissue maintenance and repair. Recently, a subset of EVs residing within the extracellular matrix has been identified. Although some roles have been proposed for matrix-bound vesicles, their role as signaling molecules within the ECM is yet to be explored. Given the close association of EVs and the ECM, it is not surprising that EVs partly mediate repair and regeneration by modulating matrix deposition and degradation through their cellular targets. This review addresses unique EV features that allow them to interact with and navigate through the ECM, describes how their release and content is influenced by the ECM, and emphasizes the emerging role of stem-cell derived EVs in tissue repair and regeneration through their matrix-modulating properties.     

Production and characterization of nanocomposites based on poly(amide-imide) containing 4,4′-methylenebis(3-chloro-2,6-diethylaniline) using nano-TiO2 surface-coupled by 3-aminopropyltriethoxysilane

In this work, the poly(amide-imide) (PAI) was synthesized from the polymerization reaction of 4,4′-methylenebis(3-chloro-2,6-diethyl trimellitimidobenzene) as a diacid with 4,4′-methylenebis(3-chloro-2,6-diethylaniline) under green condition using molten tetra-n-butylammonium bromide and triphenylphosphite. Ultrasonic technique was used for preparation of PAI/TiO₂ nanocomposites (PAI/TiO₂ NCs). For the improvement of TiO₂ nanoparticles (NPs) dispersion and enhancing interactions between NPs and polymeric matrix the surface of TiO₂ was successfully modified by silane coupling agent (3-aminopropyltriethoxysilane). The resulting NCs were characterized by FT-IR, X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). The TGA of the obtained NCs proves the enhancement in the thermal stability with an increase in the percentage of titania NPs. TEM and FE-SEM images showed that the NPs were uniformly dispersed in the polymer matrix. The shielding effect of nano TiO₂ under UV radiation was examined by UV–vis.     

Hydrothermal synthesis of pure AlPO4-5 without fluoride medium: synthesis, characterization and application as a support

Hydrothermal synthesis of pure AlPO₄-5 crystals using various reaction gels is reported. The influence of synthesis conditions on the purity of the AlPO₄-5 has been studied by changing Al sources and factors affecting the pH of the starting gel. It was observed that the additive acid to adjust the gel pH value has strongly influenced both the crystallinity and purity of the resulting AlPO₄-5 crystals. The crystals were characterized by XRD, FT-IR, TGA, BET, SEM and TPD techniques. The resulting microporous AlPO₄-5 was used as an efficient support for a functional polymer to produce an efficient heterogeneous basic nanocomposite catalyst. The catalytic activity of this novel nanocomposite was tested for Knoevenagel reaction under solvent-free conditions at room temperature. The catalyst showed a considerable degree of reusability besides very good activity.     

Effects of formulation properties on sol–gel behavior of chitosan/glycerolphosphate hydrogel

Chitosan solution containing glycerolphosphate disodium salt (Gp) is an injectable thermosensitive in situ gel-forming system which undergoes sol–gel transition under certain physiological pH and temperature conditions. When a drug-incorporated chitosan/Gp solution is injected into the body, it forms a three-dimensional gel at 37 °C, which allows the drug to be released in a sustained manner. This hydrogel can be used as a drug delivery system for prolonged release of peptides and glycopeptides. The objective of this work was to investigate the effect of different excipients on the sol–gel behavior of this thermosensitive hydrogel. Chitosan polymeric solutions (2 % w/v) containing Gp and different excipients, such as hydroxypropyl methyl cellulose (HPMC), polyethylene glycol (PEG) with two different molecular weights (PEG200 and PEG1000), and poloxamer (F127) in various concentrations, were prepared, and the pH, sol–gel transition time, and syringeability of the final solutions were evaluated. The obtained results point to HPMC as the best additive for chitosan/Gp solutions in developing an in situ gel-forming drug delivery system with optimum gelling time. A significant decrease was noted in the sol-to-gel transition time (from 90 to 60 s) when HPMC was added to the system. This may have been due to the HPMC structure which acted as a viscosity-enhancing and gel-promoting agent. The in vitro release of vancomycin hydrochloride from chitosan/Gp/HPMC hydrogel was also studied. Vancomycin release studies showed a sustained release profile for over 20 days. It can be concluded that combining chitosan/Gp and HPMC is a promising strategy for preparing a thermally reversible in situ gel-forming delivery system with an optimized gelation time.     

Dynamics and mechanisms of interfacial photoinduced electron transfer processes of third generation photovoltaics and photocatalysis

Photoinduced electron transfer (PET) across molecular/bulk interfaces has gained attention only recently and is still poorly understood. These interfaces offer an excellent case study, pertinent to a variety of photovoltaic systems, photo- and electrochemistry, molecular electronics, analytical detection, photography, and quantum confinement devices. They play in particular a key role in the emerging fields of third-generation photovoltaic energy converters and artificial photosynthetic systems aimed at the production of solar fuels, creating a need for a better understanding and theoretical treatment of the dynamics and mechanisms of interfacial PET processes. We aim to achieve a fundamental understanding of these phenomena by designing experiments that can be used to test and alter modern theory and computational modeling. One example illustrating recent investigations into the details of the ultrafast processes that form the basis for photoinduced charge separation at a molecular/bulk interface relevant to dye-sensitized solar cells is briefly presented here: Kinetics of interfacial PET and charge recombination processes were measured by fs and ns transient spectroscopy in a heterogeneous donor-bridge-acceptor (D-B-A) system, where D is a Ru(II)(terpyridyl-PO3)(NCS)3 complex, B an oligo-p-phenylene bridge, and A nanocrystalline TiO2. The forward ET reaction was found to be faster than vibrational relaxation of the vibronic excited state of the donor. Instead, the back ET occurred on the micros time scale and involved fully thermalized species. The D-A distance dependence of the electron transfer rate was studied by varying the number of p-phenylene units contained in the bridge moiety. The remarkably low damping factor beta = 0.16 angstroms(-1) observed for the ultrafast charge injection from the dye excited state into the conduction band of TiO2 is attributed to the coupling of electron tunneling with nonequilibrium vibrations redistributed on the bridge, giving rise to polaronic transport of charges from the donor ligand to the acceptor solid oxide surface.     

Self-assembled micellar nanoparticles of a novel amphiphilic cholesteryl-poly(l-lactic acid)-b-poly(poly(ethylene glycol)methacrylate) block-brush copolymer

The biodegradable cholesteryl-(l-lactic acid) _n (CPLA) was synthesized via ring opening polymerization of l-lactide in the presence of cholesterol as an initiator and the catalytic amount of Sn(Oct)₂. The resulting monohydroxyl-terminated CPLA was subsequently converted to a bromine-ended macroinitiator (CPLA-Br) by esterification with 2-bromoisobutyryl bromide. Amphiphilic block-brush copolymers with different lengths of hydrophilic block (CPLA-b-P(PEGMA)₄ and CPLA-b-P(PEGMA)₁₂) were synthesized in a subsequent atom transfer radical polymerization of the poly(ethylene glycol)monomethyl ether methacrylate (PEGMA). The prepared polymers were characterized by FTIR, ¹H NMR and GPC. The self-assembly of the copolymers into the micellar aggregates in aqueous media was followed with dynamic light scattering, transmission electron microscopy and fluorescence analysis. The CMC values of the CPLA-b-P(PEGMA)₄ and CPLA-b-P(PEGMA)₁₂ samples were estimated approximately 56 × 10^?4 and 72 × 10^?4 g/L in an aqueous solution by fluorescence probe technique, respectively. The hydrophobic/hydrophilic chain ratio of the amphiphilic copolymers could have demonstrated a correlation with micelle formation ability and inter-micellar aggregation in an aqueous solution. Using the naproxen as a hydrophobic model drug, the drug-loading efficiency and drug release properties of the CPLA–PEG nanoparticles were investigated. In vitro release study of the naproxen-loaded micelles with about 54–60 % loading efficiency and 11–12 % loading capacity was performed using dialysis method in phosphate-buffered solution at 37 °C. Accordingly, these polymeric micelles may be provided as an effective drug carrier for drug controlled release by modulating the copolymer composition and molecular weight of blocks.