Silver nanoparticles embedded temperature-sensitive nanofibrous membrane as a smart free-standing SERS substrate

To develop a smart free-standing surface enhanced Raman scattering(SERS) substrate,silver nanoparticles(AgNPs) embedded temperature-sensitive nanofibrous membrane was fabricated by electrospinning their aqueous solution containing the copolymer poly(N-isopropylacrylamide-co-Nhydroxymethylacrylamide),followed by heat treatment to form crosslinking structure within its constituent nanofibers.To avoid negative effect of the additive like stabilizer and the reactant like reductant on their SERS efficiency,the AgNPs were in-situ synthesized through reducing Ag~+ions dissolved in the polymer solution by ultraviolet irradiation.The prepared hybrid nanofibrous membrane with high stability in aqueous medium can reach its swelling or deswelling equilibrium state within 15 seconds with the medium temperature changing between 25℃and 50℃alternately.When it was used as a free-standing SERS substrate,10~(-12) mol/L of 4-nitrothiophenol in aqueous solution can be detected at room temperature,and elevating detection temperature can further lower its low detection limit.Since its generated SERS signal has desirable reproducibility,it can be used as SERS substrate for quantitative analysis.Moreover,the hybrid membrane as SERS substrate is capable of real-time monitoring the reduction of 4-nitrothiophenol into 4-aminothiophenol catalyzed by its embedded AgNPs,and the detected intermediate indicates that the reaction proceeds via a condensation route.     

Silver nanoparticles embedded temperature-sensitive nanofibrous membrane as a smart free-standing SERS substrate

Silver nanoparticles (AgNPs) embedded temperature-sensitive nanofibrous membrane as SERS substrate is capable of real-time monitoring the reduction of 4-nitrothiophenol into 4-aminothiophenol catalyzed by its embedded AgNPs, and the detected intermediate indicates that the reaction proceeds via a condensation route.     

Tunable self-assembled stereocomplexed-polylactic acid nanoparticles as a drug carrier

In this study, a model hydrophilic drug (porphyrin) was encapsulated within hydrophobic polylactic acid (PLA) nanoparticles (NPs) with different crystallinity and the relevant release behaviors were investigated. The crystalline modification was done using a modified nanoprecipitation method, where homo and stereocomplexed PLA NPs with different average diameters based on varying polymer concentrations and solvent/nonsolvent ratios (S/N) were prepared. Entrapment efficiency and drug release of sterocomplexed-PLA NPs were compared with neat poly(l -lactic acid) (PLLA) NPs. Furthermore, to get the more sustained release, porphyrin-loaded NPs were immobilized within electrospun poly(d ,l -lactide-co-glycolide (PLGA) nanofibers (NFs). Outcomes revealed that solution concentration and solvent/nonsolvent ratio play significant roles in the formation of homo and stereocomplexed NPs. On the other hand, it was found that the formation of stereocrystals did not significantly affect the size and morphology of NPs compared with neat NPs. With regard to the entrapment efficiency and drug content, stereocomplexd-PLA NPs behave relatively the same as neat PLLA NPs while the more sustained release was observed for stereocomplexed NPs. Also, it was observed that electrospinning of PLGA solution loaded by NPs led to the uniform distribution of NPs into PLGA fibers. Encapsulating the drug-loaded NPs into nanofibers decreased the rate of drug release by 50% after 24 h, compared with direct loading of drug into PLGA NFs. We conclude that it is possible to tune the entrapment efficiency and modify the release rate of the drug by giving small changes in the process parameters without altering the physical properties of the original drug substance and polymer.     

Preparation of a pH-sensitive pantoprazole-imprinted polymer and evaluation of its drug-binding and -releasing properties

The aim of this work was to synthesize a pantoprazole-imprinted polymer(MIPs)and study its binding and release properties in an aqueous media.Methacrylic acid(MAA),methacrylamide(MAAM),hydroxyethyl methacrylate(HEMA),and 4-vinyl pyridine(4VP)were tested as functional monomers.Different solvents were also applied as polymerization media under heat or UV radiation.The optimized MIP was prepared in chloroform as a solvent,4-vinyl pyridine as a functional monomer,and ethylene glycole dimethacrylate(EGDMA)as a crosslinker monomer under UV irradiation.Binding and release properties of MIP were studied in comparison with a non-imprinted polymer(NIP)in aqueous media,at different pH values.The protective effect of polymer for drugs against acidic conditions was evaluated at pH 2.Results indicated that the MIP had superior binding properties compared to NIP for pantoprazole.The percentage of drug released from MIP was significantly less than from NIP at all pH values,which was attributed to the presence of imprinted cavities in the MIP matrix.MIP also had a stronger protective effect for pantoprazole in acidic media,in comparison with NIP.     

Mesoporous porphyrinic metal-organic framework nanoparticles/3D nanofibrous scaffold as a versatile platform for bone tumor therapy

Removal of residual tumor cells and regeneration of large bone defects are urgently required after surgical resection of bone tumors. To address these issues, a bifunctional scaffold with high photothermal effect and osteogenesis was developed for bone tumor therapy. Sintered mesoporous imidazolate framework 8 (ZIF8) nanoparticles with porphyrin-like macrocycles were synthesized by calcination of ZIF8 precursors under an N₂ atmosphere. The prepared ZIF8 possesses good photothermal efficacy and drug loading capability. Phenamil (Phe), an activator of bone morphogenetic protein pathways, was encapsulated into ZIF8 before loading onto gelatin nanofibrous (GF) scaffolds. The loaded Phe exhibited sustained and near-infrared triggered release profiles, which is capable of promoting bone morphogenetic protein 2 induced osteogenic differentiation even under near-infrared treatment. Moreover, our studies revealed that the photothermal effect of GF/ZIF8-Phe scaffolds can kill MG-63 cells in vitro and inhibit subcutaneous tumor growth in vivo. Therefore, the GF/ZIF8-Phe scaffold represents a novel bifunctional platform for tumor therapy and bone regeneration.     

Preparation and evaluation of lauryl methacrylate monoliths with embedded silver nanoparticles for capillary electrochromatography

In this article, capillary columns constituted by lauryl methacrylate monoliths with embedded silver nanoparticles (AgNPs) were developed and tested. Two incorporation approaches of AgNPs in monoliths were explored. The AgNPs were either photogenerated in situ during polymerization of the monolith by UV irradiation, or incorporated to the polymerization mixture (ex situ). The influence of the AgNP concentration on the morphological and chromatographic properties of the polymer matrix was investigated, and both the in situ and ex situ approaches were comparatively discussed. The morphology of the monoliths was characterized by electron microscopic techniques, and their electrochromatographic performance was also evaluated with test mixtures of neutral compounds (sterols, fatty acid methyl esters, tocopherols, and polyaromatic hydrocarbons).     

Preparation of chitosan nanoparticles as carrier for immobilized enzyme

This work investigated the preparation of chitosan nanoparticles used as carriers for immobilized enzyme. The morphologic characterization of chitosan nanoparticles was evaluated by scanning electron microscope. The various preparation methods of chitosan nanoparticles were discussed and chosen. The effect of factors such as molecular weight of chitosan, chitosan concentration, TPP concentration, and solution pH on the size of chitosan nanoparticles was studied. Based on these results, response surface methodology was emploved. The results showed that solution pH, TPP concentration, and chitosan concentration significantly affected the size of chitosan nanoparticles. The adequacy of the predictive model equation for predicting the magnitude orders of the size of chitosan nanoparticles was verified effectively by the validation data. Immobilization conditions were investigated as well. The minimum particles size was about 42±5 nm under the optimized conditions. The optimal conditions of immobilization were as follow: one milligram of neutral proteinase was immobilized on chitosan nanoparticles for about 15 min at 40°C. Under the optimized conditions, the enzyme activity yield was 84.3%.     

Preparation and biological evaluation of radiolabeled-folate embedded superparamagnetic nanoparticles in wild-type rats

In this study, superparamagnetic iron oxide nanoparticles (SPION) embedded by folic acid (SPION-folate) were prepared by a modified co-precipitation method. The structure, size, morphology, magnetic property and relaxivity of the SPION-folate were characterized systematically by means of XRD, VSM, HRSEM and TEM and the interaction between folate and iron oxide (Fe₃O₄) was characterized by FT-IR. The particle size was shown to be ≈5–10 nm. To ensure biocompatibility, the interaction of these SPION with mouse connective tissue cells (adhesive) was investigated using an MTT assay. Consequently, gallium-67 labeled nanoparticles ([⁶⁷Ga]-SPION-folate) were prepared using ⁶⁷Ga with a high labeling efficiency (over 96%, RTLC method) and they also showed an excellent stability at room temperature for at least 2 days and were evaluated for their biodistribution in normal rats up to 24 h compared with free Ga³⁺ cation and [⁶⁷Ga]-SPION biodistribution. The biodistribution of the tracer among 3 other folate tracers were compared, showing lower liver uptake and higher blood circulation after 24 h leading to better bioavailability. The bone:muscle, kidney:muscle, lung:muscle, stomach:muscle ratios were 9.3, 9.32, 7.6 and 5.83 respectively. The developed folate-containing nano-system can be an interesting folate receptor tracer, capable of better cell membrane permeability while possessing paramagnetic properties for thermotherapy.     

Self-aggregated nanoparticles of cholesterol-modified glycol chitosan conjugate: Preparation, characterization, and preliminary assessment as a new drug delivery carrier

Cholesterol-modified glycol chitosan (CHGC) conjugate was synthesized and characterized by FTIR and ¹H NMR. The degree of substitution (DS) was 6.7 cholesterol groups per 100 sugar residues of glycol chitosan. CHGC formed self-aggregated nanoparticles with a roughly spherical shape and a mean diameter of 228 nm by probe sonication in aqueous medium. The physicochemical properties of the self-aggregated nanoparticles were studied using dynamic light scattering (DLS), transmission electron microscopy (TEM) and fluorescence spectroscopy. The critical aggregation concentration (CAC) of self-aggregated nanoparticles in aqueous solution was 0.1223 mg/mL. Indomethacin (IND), as a model drug, was physically entrapped into the CHGC nanoparticles by dialysis method. The characteristics of IND-loaded CHGC (IND-CHGC) nanoparticles was analyzed using DLS, TEM and high performance liquid chromatography (HPLC). The IND-CHGC nanoparticles were almost spherical in shape and their size increased from 275 to 384 nm with the IND-loading content increasing from 7.14% to 16.2%. The in vitro release behavior of IND from CHGC nanoparticles was studied by a dialysis method in phosphate buffered saline (PBS, pH 7.4). IND was released in a biphasic way. The initial rapid release in 2 h and slower release for up to 12 h were observed. The results indicated that CHGC nanoparticles had a potential as a drug delivery carrier.     

Preparation of bismuth sulfide nanoparticles as targeted biocompatible nano-radiosensitizer and carrier of methotrexate

In this study, Bi₂S₃@BSA–Bio–MTX nanoparticles (NPs) were synthesized for the first time by bovine serum albumin (BSA)-mediated biomineralization (Bi₂S₃@BSA NPs) followed by covalent bonding of biotin (Bio) and methotrexate (MTX) on the surface of the Bi₂S₃@BSA NPs via carbodiimide chemistry. The synthesized NPs were globular and exhibited uniform morphology with a hydrodynamic diameter of 107.6 ± 6.81 nm (mean ± standard deviation) and zeta potential of −20.9 ± 2.18 mV. Drug release from Bi₂S₃@BSA–Bio–MTX NPs indicated an enzyme-dependent release pattern. The in vitro biocompatibility of NPs was confirmed by investigating their cytotoxicity against the HEK-293 cell line and hemolysis assay test, whereas the in vivo biocompatibility of the NPs was evaluated and confirmed by the lethal dose 50 (LD₅₀) test. To evaluate the in vitro anticancer activity of the functionalized NPs and MTX, their cytotoxic effects was assessed against 4T1 cancer cells by 5-dimethylthiazol-z-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with and without X-ray radiation. Results showed that Bi₂S₃@BSA–Bio–MTX NPs have excellent anticancer activity, especially following X-ray radiation.     

A novel dual thermo- and pH-responsive silver nanocomposite hydrogel as a drug delivery system

The purpose of this study was to develop a novel dual thermo- and pH-responsive silver nanocomposite hydrogel (SNH) for drug release applications. This smart SNH was prepared in a facile one-pot method by in situ reduction of silver ions in salep solution and then grafting of poly(vinylpyrrolidone-co-acrylic acid) onto it. The SNH was characterized by transmission electron microscopy (TEM), scanning electron microscopy with energy-dispersive X-ray analysis (SEM–EDAX), thermo-gravimetric analysis (TGA), Fourier transform infrared (FT-IR), UV–Vis spectroscopy, and cyclic voltammetry. The dependence of swelling properties of the prepared SNH on the reaction variables (such as monomer, Ag NO₃, and cross-linker concentrations), temperature, pH, and salt was investigated. The potential of obtained SNH was examined for the deferasirox release from prepared hydrogel under different temperatures and pHs. The evaluation of release mechanism and determination of diffusion coefficients were also studied. In addition, SNH showed good antibacterial potentials. The results of this study provide valuable information regarding the development of dual stimuli-sensitive SNH for biomedical applications.     

嵌段共聚物核交联胶束的制备与载药性能研究

在DMAP的催化和DIPC的作用下,丙烯酸的双键被引入聚乙二醇-聚己内酯嵌段共聚物的疏水链段上,制备胶束过程中使用过硫酸铵催化位于胶束内核部分的双键交联,得到的核交联胶束。在包载甲氨喋呤释放过程中,核交联胶束的累积释放率明显比非核交联胶束的小,具有良好的缓释效果。     

In vitro and in vivo evaluation of silk fibroin-hardystonite-gentamicin nanofibrous scaffold for tissue engineering applications

Designing advanced biomaterials with regenerative and drug delivering functionalities remains a challenge in the field of tissue engineering. In this paper we present the design, development, and a use case of an electrospun nano-biocomposite scaffold composed of silk fibroin (SF), hardystonite (HT), and gentamicin (GEN). The fabricated SF nanofiber scaffolds provide mechanical support while HT acts as a bioactive and drug carrier, on which GEN is loaded as an antibacterial agent. Antibacterial zone of inhibition (ZOI) results indicate that the inclusion of 3–6 wt% GEN significantly improves the antibacterial performance of the scaffolds against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria, with an initial burst release of 10–20% and 72–85% total release over 7 days. The release rate of stimulatory silicon ions from SF-HT scaffolds reached 94.53±5 ppm after 7 days. Cell studies using osteoblasts show that the addition of HT significantly improved the cytocompatibility of the scaffolds. Angiogenesis, in vivo biocompatibility, tissue vascularization, and translatability of the scaffolds were studied via subcutaneous implantation in a rodent model over 4-weeks. When implanted subcutaneously, the GEN-loaded scaffold promoted angiogenesis and collagen formation, which suggests that the scaffold may be highly beneficial for further bone tissue engineering applications.     

Novel nanoparticles composed of chitosan and β-cyclodextrin derivatives as potential insoluble drug carrier

This research was aim to develop novel cyclodextrin/chitosan(CD/CS) nanocarriers for insoluble drug delivery through the mild ionic gelation method previously developed by our lab. A series of different bcyclodextrin(β-CD) derivatives were incorporated into CS nanoparticles including hydroxypropyl-bcyclodextrin(HP-β-CD), sulphobutylether-β-cyclodextrin(SB-β-CD), and 2,6-di-O-methy-β-cyclodextrin(DM-β-CD). Various process parameters for nanoparticle preparation and their effects on physicochemical properties of CD/CS nanoparticles were investigated, such as the type of CD derivatives,CD and CS concentrations, the mass ratio of CS to TPP(CS/TPP), and p H values. In the optimal condition,CD/CS nanoparticles were obtained in the size range of 215–276 nm and with the zeta potential from30.22 m V to 35.79 m V. Moreover, the stability study showed that the incorporation of CD rendered the CD/CS nanocarriers more stable than CS nanoparticles in PBS buffer at p H 6.8. For their easy preparation and adjustable parameters in nanoparticle formation as well as the diversified hydrophobic core of CD derivatives, the novel CD/CS nanoparticles developed herein might represent an interesting and versatile drug delivery platform for a variety of poorly water-soluble drugs with different physicochemical properties.     

Preparation and characterization of a novel magnetized nanosphere as a carrier system for drug delivery using Plantago ovata Forssk. hydrogel combined with mefenamic acid as the drug model

The aim of the present study was to magnetize Plantago ovata Forssk. hydrogel and produce a nanosphere system to carrier mefenamic acid as the drug model. For this propose, P. ovata seeds hydrogel (POSH) was extracted and magnetized by Fe₃O₄ being functionalized using tetraethyl orthosilicate and trimethoxyvinysilane. Thereafter, mefenamic acid (MFA) was loaded on the carrier system. The final product, as the magnetic drug loaded nanosphere (Fe/POSH/MFA), was fully characterized through different techniques involving X-ray diffraction (XRD), scanning electron microscopy (SEM), vibrating-sample magnetometer (VSM), thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and FT-IR spectroscopy. The results confirmed the successful production of the drug loaded nanosphere system with particles magnetization of 25 emu/g over a range size of 40–50 nm. However, the size distribution less than 100 nm was measured through DLS analysis. The hydrogel showed a pH sensitivity swelling behavior representing the best efficacy at pH 7.4. The efficiency of the drug encapsulation was found to be 64.35%. The drug releasing was studied using a dialysis bag at pH = 7.4. The highest in vitro drug releasing was found to be 57.3 ± 0.6% after 72 h, as well. The findings of the current report account for the potential use of P. ovata hydrogel as an effective delivery system for encapsulation of water insoluble basic drugs, e.g., MFA in a magnetized carrier system.     

Preparation of hierarchical hollow CaCO3 particles and the application as anticancer drug carrier

One-pot approach to couple the crystallization of CaCO(3) nanoparticles and the in situ symmetry-breaking assembly of these crystallites into hollow spherical shells was developed under the templating effect of a soluble starch. Further functional study using HP-a as an anticancer drug carrier (DOX) demonstrated its advantages for localizing drug release by the pH value-sensitive structure and enhancing cytotoxicity by increasing cellular uptake, perinuclear accumulation, and nuclear entry.     

Synthesis of thermo- and pH-sensitive star-shaped poly(2-alkyl-2-oxazoline) and its properties in aqueous its properties in aqueous solutions with varying medium acidity

Abstract

pH-sensitive eight-arm star-shaped polymer with calix[8]arene core and block copolymer of poly(2-methoxycarbonylethyl-2-oxazoline) and poly(2-isopropyl-2-oxazoline) arms was synthesized for the first time. The block composition was 1:1 and molar mass was 24000?g?mol^?1. The behavior of synthesized star in aqueous solutions was analyzed by turbidity and light scattering at the pH values from 2 to 12.2. It is shown that in an organic solvent, the polymer molecule has a low shaped asymmetry. In aqueous solutions, the synthesized star exhibits thermosensitivity with a lower critical solution temperature. It was found that at low temperature in solutions, there were macromolecules and aggregates which were formed due to interaction of hydrophobic cores. The phase separation temperatures did not depend on pH in basic media and decreased strongly at pH <5.     

Dendrimer-like supramolecular nanovalves based on polypseudorotaxane and mesoporous silica-coated magnetic graphene oxide: a potential pH-sensitive anticancer drug carrier

In the present research, two types of drug carriers based on mesoporous silica-coated magnetic graphene oxide, Fe₃O₄@GO@mSiO₂, were synthesised and the pH-responsive behaviour for doxorubicin release was investigated. One type of the carrier was dendrimer-like multi ethylene amine grafted on Fe₃O₄@GO@mSiO₂ and the other was dendrimer-like supramolecular polypseudorotaxane. Herein, α-cyclodextrin was used in the structure of supramolecular nanoparticles as a gatekeeper to inhibit the drug from escaping at neutral pH (the pH of healthy tissue). The drug release profile showed that the supramolecular nanocarrier was more sensitive to the pH changes. The content of drug release was about 100% at pH 5.5 (endosomal pH) during 48 h; but it was zero at pH 7.4. Also, the dendrimer structure facilitated the triggered release of doxorubicin.