Preparation and characterization of L-Leucine-modified amphiprotic bifunctional mesoporous SBA-15 molecular sieve as a drug carrier for ribavirin

In this study, an amphiphilic bifunctional mesoporous SBA-15 material (AMPBIF-SBA-15) was synthesized through post-synthesis method as a drug carrier. Ribavirin was selected as the model drug and whose release from both unmodified and functionalized SBA-15 was evaluated in four media solutions with different pH or ionic strength. The release process indicated that AMPBIF-SBA-15 was a pH-sensitive drug carrier, which showed a phased low-release effect to ribavirin in the simulated body fluid (PBS, pH 7.4) solution. The materials were further characterized by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-desorption measurements and elemental analysis. This study provided a novel drug carrier for ribavirin to improve curative effect of ribavirin.     

Surface-modified mesoporous silica with ferrocene derivatives and its ultrasound-triggered functionality

Novel ferrocene derivatives designed as gatekeepers were successfully composed on the pore outlet of amino-functionalized mesoporous silica by post-synthesis grafting where the peptide bond of the amine group (-NH₂) of mesoporous silica was linked with the carboxylic acid group (-COOH) of both ends of the ferrocene derivatives. The materials of the amine-functionalized mesoporous silica (NH₂-MS) and ferrocene-functionalized mesoporous silica (Fc-CONH-MS) were characterized using X-ray diffractions (XRD), Fourier-transform infrared (FT-IR), N₂ sorption isotherms, solid-state NMR spectra, scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM), and UV-vis absorption spectra. The ferrocene attached to the mesoporous silica pore outlet was cleavaged by ultrasound irradiation, which opened the closed-pore outlets, suggesting a possible application for controlled release drug carrier.     

Nanoparticle carriers based on copolymers of poly(<Emphasis Type="SmallCaps">l</Emphasis>-aspartic acid co-<Emphasis Type="SmallCaps">l</Emphasis>-lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine for drug delivery

A novel poly(l-aspartic) derivative (PAL-DPPE) containing polylactide and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) segments has been successfully synthesized. The chemical structures of the copolymers were confirmed by Fourier-transform infrared spectroscopy (FTIR), NMR (¹H NMR, ¹³C NMR, ³¹P NMR), and thermogravimetric analysis (TGA). Fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) confirmed the formation of micelles of the PAL-DPPE copolymers. In order to estimate the feasibility as novel drug carriers, an anti-tumor model drug doxorubicin (DOX) was incorporated into polymeric micelles by double emulsion and nanoprecipitation method. The DOX-loaded micelle size, size distribution, and encapsulation efficiency (EE) were influenced by the feed weight ratio of the copolymer to DOX. In addition, in vitro release experiments of the DOX-loaded PAL-DPPE micelles exhibited that faster release in pH 5.0 than their release in pH 7.4 buffer. The poly(l-aspartic) derivative copolymer was proved to be an available carrier for the preparation of micelles for anti-tumor drug delivery.     

Functional and unmodified MWNTs for delivery of the water-insoluble drug Carvedilol - A drug-loading mechanism

The purpose of this study was to develop carboxyl multi-wall carbon nanotubes (MWNTs) and unmodified MWNTs loaded with a poorly water-soluble drug, intended to improve the drug loading capacity, dissolubility and study the drug-loading mechanism. MWNTs were modified with a carboxyl group through the acid treatment. MWNTs as well as the resulting functionalized MWNTs were investigated as scaffold for loading the model drug, Carvedilol (CAR), using three different methods (the fusion method, the incipient wetness impregnation method, and the solvent method). The effects of different pore size, specific surface area and physical state were systematically studied using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), nitrogen adsorption, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The functional MWNTs allowed a higher drug loading than the unmodified preparations. The methods used to load the drug had a marked effect on the drug-loading, dissolution, and physical state of the drug as well as its distribution. In addition, the solubility of the drug was increased when carried by both MWNTs and functional MWNTs, and this might help to improve the bioavailability.     

Synthesis and characterization of the SnS nanowires via chemical vapor deposition

Single-crystal SnS nanowires have been successfully synthesized by catalysis-assistant chemical vapor deposition. Applying Au nanoparticles which were applied on the ITO surface as the catalysator, using SnS powder and S powder as precursors and the Ar+H₂ mixed atmosphere as the shielding and carrier gas, the SnS nanowires were obtained. X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectra (XPS) and Raman spectroscopy were employed to characterize the as-synthesized SnS nanostructures. The room-temperature photoluminescence properties of these as-prepared SnS nanowires were presented.     

Characterization and scanning electron microscopic investigation of crosslinked freeze dried gelatin matrices for study of drug diffusivity and release kinetics

Drug delivery is a promising technique to enhance the therapeutic efficacy of the drug. However, properties of carrier materials require intense improvement for effective transport of drug molecules. In the current study, attempts have been made to develop freeze dried gelatin matrices cross linked with genipin at various temperatures (5°C, 15°C and 25°C) prior to freeze-drying (-80°C). The freeze dried matrices thus obtained at the said temperatures are characterized for crosslinking density, compression strength, swelling behaviors. The matrix crosslinked at 25°C showed highest Flory-Rehner crosslinking density (467 ± 46) (p<0.05), highest compressive strength (12.36 ± 0.12) (p<0.05) and lowest equilibrium water content. In this context, scanning electron microscopy (SEM) was performed to study the surface morphology (size and shape of pores) of the crosslinked matrices. These images were further processed for quantitative analysis of morphological features, viz., areas, radius, ferret diameter, length of major and minor axis and eccentricity using MATLAB toolboxes. These quantitative analyses correlate transport and the release kinetics of model anti-inflammatory drug (indomethacin) from crosslinked matrices in vitro to tune as a controllable delivery system. The diffusional exponent (n) for all constructs ranging from 0.61 to 0.69 (p<0.05) (0.45相似文献   

Coaxial Electrospun Poly(L‐Lactic Acid) Ultrafine Fibers for Sustained Drug Delivery

A coaxial electrospinning technique to fabricate core‐shell ultrafine fiber mats for drug delivery application is described in this paper. Poly (L‐lactic acid) (PLLA) and tetracycline hydrochloride (TCH) were employed as the shell and core materials, respectively. To investigate the feasibility of the resulting fiber mats for use as drug release carriers, these electrospun fibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and tensile testing. In vitro drug release behavior was also examined by ultraviolet‐visible (UV‐VIS) spectroscopy. Results indicated that a reservoir‐type drug release device can be conveniently obtained through encapsulating TCH in the PLLA ultrafine fiber. The size of the ultrafine fibers had a significant effect on their physical‐chemical properties. Furthermore, a sustained TCH release from these fiber mats was also observed. Consequently, the electrospun ultrafine fiber mats containing drugs may be used as drug release carriers or made into biomedical devices such as sutures and wound dressings.     

Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

Transdermal drug delivery(TDD) can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow–green fluorescent nanoparticles and high molecular weight hyaluronic acid(HA) in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that,with the application of ultrasound exposures, the permeability of the skin to these markers(e.g., their penetration depth and concentration) could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents(UCAs). When the ultrasound was applied without UCAs,low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 μm. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 μm, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4–5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications(e.g., nanoparticle drug carriers, transdermal patches and cosmetics), protocols and methods presented in this paper are potentially useful.     

Lysozyme microspheres incorporated with anisotropic gold nanorods for ultrasound activated drug delivery

We report on the fabrication of lysozyme microspheres (LyMs) incorporated with gold nanorods (NRs) as a distinctive approach for the encapsulation and release of an anticancer drug, 5-Fluorouracil (5-FU). LyMs with an average size of 4.0 ± 1.0 µm were prepared by a sonochemical method and characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR). The LyMs were examined using hydrophobic (nile red) as well as hydrophilic (trypan blue) dyes under confocal laser scanning microscopy (CLSM) to obtain information about the preferential distribution of fluorescent molecules. Notably, the fluorescent molecules were accumulated in the inner lining of LyMs as the core was occupied with air. The encapsulation efficiency of 5-FU for LyMs-NR was found to be ∼64%. The drug release from control LyMs as well as LyMs incorporated with NRs was investigated under the influence of ultrasound (US) at 200 kHz. The total release for control LyMs and LyMs incorporated with gold NRs was found to be ∼70 and 95% after 1 h, respectively. The density difference caused by NR incorporation on the shell played a key role in rupturing the LyMs-NR under US irradiation. Furthermore, 5-FU loaded LyMs-NR exhibited excellent anti-cancer activity against the THP-1 cell line (∼90% cell death) when irradiated with US of 200 kHz. The enhanced anti-cancer activity of LyMs-NR was caused by the transfer of released 5-FU molecules from bulk to the interior of the cell via temporary pores formed on the surface of cancer cells, i.e., sonoporation. Thus, LyMs-NR demonstrated here has a high potential for use as carriers in the field of drug delivery, bio-imaging and therapy.     

Antimicrobial and antitumor activities of 1,2,4‐triazoles/polypyrrole chitosan core shell nanoparticles

Combination of natural biodegradable polymer with a synthetic polymer offers excellent properties for the support in drug delivery system. For this purpose, biodegradable conductive nanoparticle polypyrrole based on chitosan (PPC) has been prepared via oxidative polymerization of pyrrole in presence of chitosan using FeCl₃ as oxidant in acidic medium and used as a carrier for 1,2,4‐triazoles. The resultant nanoparticles were characterized by X‐ray diffraction, Fourier transform infrared analysis, transmission electron microscopy, scanning electron microscopy, and thermal gravimetric analysis. The results indicate that spherical nanoparticle of average diameter 52 ± 8 nm was successfully prepared. The spherical particles were composed of dark sphere surrounded by grey shell. A circumferential dark ring is observed in the shell after loading 1,2,4‐triazoles into PPC nanoparticles. The loaded triazoles were released almost linearly against time in a sustained fashion into different pH media. The mechanism of triazoles release was determined using different kinetics equations. The antibacterial activities against the gram‐negative and gram‐positive bacteria were examined. Furthermore, the antitumor activity of PPC nanoparticles loaded 1,2,4‐triazoles was also examined against Ehrlich ascites carcinoma cells and breast cancer cell line (MCF7). Polypyrrole chitosan loaded nanoparticles exhibited higher antitumor activity than 1,2,4‐triazoles.     

GQDs-MSNs nanocomposite nanoparticles for simultaneous intracellular drug delivery and fluorescent imaging

Although number of stimuli-responsive drug delivery systems based on mesoporous silica nanoparticles (MSNs) have been developed, the simultaneous real-time monitoring of carrier in order to guarantee proper drug targeting still remains as a challenge. GQDs-MSNs nanocomposite nanoparticles composed of graphene quantum dots (GQDs) and MSNs are proposed as efficient doxorubicin delivery and fluorescent imaging agent, allowing to monitor intracellular localization of a carrier and drug diffusion route from the carrier.Graphene quantum dots (average diameter 3.65?±?0.81 nm) as a fluorescent agent were chemically immobilized onto mesoporous silica nanoparticles (average diameter 44.08?±?7.18 nm) and loaded with doxorubicin. The structure, morphology, chemical composition, and optical properties as well as drug release behavior of doxorubicin (DOX)-loaded GQDs-MSNs were investigated. Then, the in vitro cytotoxicity, cellular uptake, and intracellular localization studies were carried out. Prepared GQDs-MSNs form stable suspensions exhibiting excitation-dependent photoluminescence (PL) behavior. These nanocomposite nanoparticles can be easily DOX-loaded and show pH- and temperature-dependent release behavior. Cytotoxicity studies proved that GQDs-MSNs nanocomposite nanoparticles are nontoxic; however, when loaded with drug, they enable the therapeutic activity of DOX via its active delivery and release. GQDs-MSNs owing to their fluorescent properties and efficient in vitro cellular internalization via caveolae/lipid raft-dependent endocytosis show a high potential for the optical imaging, including the simultaneous real-time optical tracking of the loaded drug during its delivery and release.

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Facile Synthesis of Single‐Phase Mesoporous Gd2O3:Eu Nanorods and Their Application for Drug Delivery and Multimodal Imaging

In this work, a new and facile strategy is developed to synthesize a single‐phase Eu³⁺‐doped mesoporous gadolinium oxide nanorods (MS‐Gd₂O₃:Eu@PEG) by incorporating a facile wet‐chemical route, which includes an induced silica layer being coated onto the nanorods, and evolution of pores and formation of channels, as well as a surface‐modified process for multimodal imaging and anti‐cancer drug delivery. The properties of these as‐prepared Gd₂O₃:Eu nanorods are characterized by transmission electron microscopy (TEM), X‐ray diffraction (XRD), N₂ adsorption/desorption, and photoluminescence (PL). The in vitro cytotoxicity test, drug loading, and drug release experiments reveal that the MS‐Gd₂O₃:Eu@PEG nanorods have good biocompatibility, efficient loading capacity, and pH‐sensitive releasing behavior, suggesting the nanorods could be an ideal candidate as drug delivery vehicles for cancer therapy. Furthermore, the MS‐Gd₂O₃:Eu@PEG nanorods show clearly dose‐dependent contrast enhancement in T₁‐weighted magnetic resonance images and can potentially be used as a T₁‐positive contrast agent. These results indicate our prepared multifunctional mesoporous gadolinium oxide nanorods can serve as a promising platform for simultaneous anti‐cancer drug delivery and multimodal imaging.     

Naproxen drug delivery using periodic mesoporous silica SBA-15

In this paper, we present the release of naproxen from hexagonal periodic mesoporous silica SBA-15, which serves as a drug delivery system. Naproxen, the well-known nonsteroidal anti-inflammatory drug (NSAID), was loaded into the pores of SBA-15 silica modified with aminopropyl groups. The physicochemical properties of the modified sample (A-SBA-15/napro) were compared with the unmodified SBA-15 mesoporous silica loaded with the drug (SBA-15/napro). The kinetic of the naproxen release into the physiological solution was studied. The released amount of naproxen represented 90.7% from the unmodified SBA-15 in 72 h, while from the sample A-SBA-15/napro the released amount represented about 80.9%. The prepared materials were characterized by nitrogen adsorption/desorption, Small angle X-ray scattering (SAXS), Fourier-transform infrared spectroscopy (FT-IR) and the thermoanalytical methods (TG/DTA). Thin layer chromatography (TLC) was used for quantitative determination of the released naproxen.     

Magnetic iron oxide nanoparticle-hollow mesoporous silica Spheres:Fabrication and potential application in drug delivery

A facile method is developed for the fabrication of magnetic iron oxide nanoparticle-hollow mesoporous silica spheres (IONP-HMSs) and explored their potential application in drug delivery. Through the self-assembling process of IONPs and the formation of mesoporous silica shells, the IONP-HMSs with hollow interior cavity were obtained. The cetyltrimethyl ammonium bromide (CTAB) encapsulated IONP-containing spheres served as the template to establish the mesoporous silica shells. Typical anti-cancer drug, doxorubicin hydrochloride (DOX) was applied for drug loading and release process of IONP-HMSs, which demonstrated the IONP-HMSs have a high drug loading efficiency and allow pH-trigged release of DOX in vitro. Moreover, the IONP-HMSs exhibited excellent biocompatibility and enhanced DOX therapeutic efficacy to HeLa cells. Compared with traditional methods, the reported microemulsion-based method for the synthesis of IONP-HMSs enables the formation of hollow-structured nanocomposite without any complex template-removing process, which could pave the way to improving the therapeutic efficacy in drug delivery system.     

两亲性壳聚糖基聚合物碳点的合成及其在载药方面的应用

通过水热法合成了系列具有高荧光量子产率（42.9%）辛基化壳聚糖基两亲性聚合物碳点荧光材料。利用红外光谱、紫外吸收光谱、光电子能谱、透射电镜、X射线衍射及荧光光谱对聚合物碳点进行了表征。以阿霉素为模型药物,研究了聚合物碳点对阿霉素的载药性能。当辛基取代度为76.42%时,其最大载药量和包封率分别为49.6%与47.4%。在磷酸盐缓冲液中,载药纳米胶束呈前期快速释放,后期缓慢释放的双相特征。将载药纳米胶束与鼻咽癌细胞作用,发现其存活率随着载药纳米胶束加入量的增加而降低,说明该纳米胶束对鼻咽癌细胞有一定的抑制作用。总之,该聚合物碳点材料在药物载体与荧光示踪方面有潜在的应用价值。     

Mesoporous silica-coated NaYF4:Yb3+, Er3+ particles for drug release

NaYF₄:Yb³⁺, Er³⁺ nanoparticles were successfully prepared by a polyol process using diethyleneglycol (DEG) as solvent. These NaYF₄:Yb³⁺, Er³⁺ nanoparticles can be coated with mesoporous silica using nonionic triblock copolymer EO₂₀PO₇₀EO₂₀ (P 123) as structure-directing agent and other materials. The composites can load ibuprofen and release the drug in the phosphate buffer solution (PBS). The composites were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen absorption/desorption isotherms, fluorescence spectra, and UV/Vis absorption spectra, respectively. The composites have the mesoporous structure. In addition, the composites emit red fluorescence (from Er³⁺) under 980 nm near infrared laser excitation, which can be used as fluorescent probes in the drug-delivery system.     

A new approach to the drug release kinetics of a discrete system: SiO2 system obtained by ultrasonic dry spraying

Mesoporous silica materials have already proved to be non-toxic and biocompatible, and also to have large pore volume and very high specific surface area suitable for loading of small molecules. Having this in mind and the fact that silicon dioxide (SiO₂) powders can be so designed to obtain particle structures organized at multi levels, SiO₂ was chosen as a potential carrier for metronidazole, an antibiotic drug. SiO₂ powder was synthesized in two stages: first silica sol was prepared by hydrothermal synthesis and second the sol was converted into powder by dry spraying with simultaneous incorporation of the antibiotic into its structure. Scanning and transmission electron microscopy study revealed very complex structure and sub-structure of SiO₂ particles. Cell viability tests were used for estimation of cytotoxicity of so synthesized SiO₂. The drug release data showed that the system can provide drug release for a long time. Also, the device behavior is fully predictable, according to our theoretical model of multilevel structure design, and gives many opportunities for model investigations of drug release and its kinetics. The pore sizes and their distribution were observed as a limiting factor of drug release kinetics. Therefore, as the pore sizes are given as a set of discrete values, the kinetics of drug release might also be given as a set of corresponding discrete values.     

Novel insights into controlled drug release from coated pellets by confocal Raman microscopy

The development of novel therapeutics with improved efficacy implies increasing complexity of drug delivery systems, which in turn require advanced methods for their analytical characterization. Among these systems, pellets represent upcoming carrier systems, which show several advantages like simplified dosing and improved compliance among children and the aged population. However, rational development of such systems is hampered by the lack of non‐destructive, chemically selective analytical insight into compound distribution and drug release mechanisms. The aim of this study was to evaluate confocal Raman microscopy (CRM) for investigation of coated drug‐loaded pellets based on visualization of compound distribution and elucidation of drug release mechanisms. Three complementary approaches were applied for pellet characterization: analysis of cross sections after bisectioning, non‐invasive visualization of the pellet surface, and virtual cross sectioning in x–z direction. As the surface of such pellets is structured, a complementary approach of optical topography and CRM was applied for three‐dimensional analysis. Based on the individual Raman peak patterns, the drug and excipients forming the matrix of the pellets and the film coating were successfully visualized with high spatial resolution, verifying homogeneous drug distribution and intact polymer coating of the pellet. Further, analysis of the pellets after certain time intervals during drug release testing revealed pore formation in the polymer coating facilitating drug release and preceding drug depletion in the pellets matrix. CRM represents an upcoming technique for analytical characterization of carrier systems and elucidation of their complex drug release mechanisms, thus supporting rational development of novel therapeutics. Copyright © 2016 John Wiley & Sons, Ltd.     

A novel method for preparation of 8-hydroxyquinoline functionalized mesoporous silica: Aluminum complexes and photoluminescence studies

8-Hydroxyquinoline (8-HQ) was attached to mesoporous silica by sulfonamide bond formation between 8-hydroxyquinoline-5-sulfonyl chloride (8-HQ-SO₂Cl) and aminopropyl functionalized SBA-15 (designated as SBA-SPS-Q) and then aluminum complexes of 8-HQ was covalently bonded to SBA-SPS-Q using coordinating ability of grafted 8-HQ.The prepared materials were characterized by powder X-ray diffraction (XRD), nitrogen adsorption-desorption, Fourier transform infrared (FT-IR), thermal analysis (TGA-DTA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), elemental analysis and fluorescence spectra. The environmental effects on the emission spectra of grafted 8-HQ and its complexes were studied and discussed in details.