Preparation of luminescent and mesoporous Eu3+/Tb3+ doped calcium silicate microspheres as drug carriers via a template route

Luminescent and mesoporous Eu(3+)/Tb(3+) doped calcium silicate microspheres (LMCS) were synthesized by using mesoporous silica spheres as the templates. The LMCS and drug-loaded samples were characterized by means of X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), N(2) adsorption/desorption, and photoluminescence (PL) spectra. The results reveal that the LMCS have uniform spherical morphology with a diameter around 400 nm and the mesopore size of 6 nm. The prepared samples exhibit little cytotoxicity at concentrations below 5 mg mL(-1) via MTT assay. In addition, drug storage/release properties of the LMCS were demonstrated for ibuprofen (IBU). The obtained LMCS can be used to encapsulate drugs and release them. Under excitation by UV light, the IBU-loaded samples still show the characteristic (5)D(0)-(7)F(1-3) emission lines of Eu(3+) and the characteristic (5)D(4)-(7)F(3-6) emission lines of Tb(3+). The PL intensity of Eu(3+) in the drug carrier system increases with the cumulative released amount of IBU, making the drug release able to be tracked or monitored by the change of luminescence of Eu(3+). The LMCS reported here with mesoporous structure, good biocompatibility and luminescent property can be a promising drug delivery carrier.     

Luminescent, mesoporous, and bioactive europium-doped calcium silicate (MCS: Eu3+) as a drug carrier

Luminescent, mesoporous, and bioactive europium-doped calcium silicate (MCS: Eu) was successfully synthesized. The obtained MCS: Eu(3+) was performed as a drug delivery carrier to investigate the drug storage/release properties using ibuprofen (IBU) as the model drug. The structural, morphological, textural, and optical properties were well characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N(2) adsorption/desorption, and photoluminescence (PL) spectra, respectively. The results reveal that the MCS: Eu exhibits the typical ordered characteristics of the mesostructure. This composite shows a sustained release profile with IBU as the model drug. The IBU-loaded samples still present red luminescence of Eu(3+) ((5)D(0)-(7)F(1,2)) under UV irradiation. The emission intensities of Eu(3+) in the drug carrier system vary with the amount of released IBU, making the drug release easily tracked and monitored. The system demonstrates a great potential for drug delivery and disease therapy.     

Porous YAG:Nd3+ fibers with excitation and emission in the human "NIR optical window" as luminescent drug carriers

The design and preparation of luminescent drug carriers has been a prosperous area of research for many years. However, the excitation and/or emission wavelength of such luminescent drug carriers haven't been optimized in the so-called human "near infrared (NIR) optical window", thus restricting their practical applications. Herein, we report the synthesis of electrospun porous YAG:Nd(3+) (neodymium-doped yttrium aluminum garnet) fibers with both excitation and emission in the "NIR optical window" as luminescent drug carriers. The YAG:Nd(3+) porous fibers were characterized by SEM, TEM, XRD, scanning transmission electron microscopy-energy-dispersive X-ray spectroscopy (STEM-EDX), and photoluminescence (PL). Ibuprofen (IBU) was used as a model drug to evaluate the drug-loading capacities and release profiles of the samples. BMSCs (bone mesenchymal stem cells) were used as model human cells to investigate cytotoxicity. Our results indicated that the YAG:Nd(3+) fibers possessed a fine, irregularly porous fibrous morphology with an average diameter of 378 nm. The florescence of the sample (1064 nm) could be excited over a wide wavelength range in the NIR region. During the release process of IBU in simulated body fluid (SBF), along with the dissolving of the drug, the solvent entered into the pores, and the emission intensity of the YAG:Nd(3+) fibers at 1064 nm decreased gradually, owing to a quenching effect of the hydroxy groups, thus provided an approach to track and monitor drug release. In addition, cytotoxicity investigations revealed that these YAG:Nd(3+) fibers were biocompatible with human cells. Consequently, the porous YAG:Nd(3+) fibers are a promising material for applications as advanced drug carriers.     

Porous YAG:Nd3+ Fibers with Excitation and Emission in the Human “NIR Optical Window” as Luminescent Drug Carriers

The design and preparation of luminescent drug carriers has been a prosperous area of research for many years. However, the excitation and/or emission wavelength of such luminescent drug carriers haven′t been optimized in the so‐called human “near infrared (NIR) optical window”, thus restricting their practical applications. Herein, we report the synthesis of electrospun porous YAG:Nd³⁺ (neodymium‐doped yttrium aluminum garnet) fibers with both excitation and emission in the “NIR optical window” as luminescent drug carriers. The YAG:Nd³⁺ porous fibers were characterized by SEM, TEM, XRD, scanning transmission electron microscopy–energy‐dispersive X‐ray spectroscopy (STEM‐EDX), and photoluminescence (PL). Ibuprofen (IBU) was used as a model drug to evaluate the drug‐loading capacities and release profiles of the samples. BMSCs (bone mesenchymal stem cells) were used as model human cells to investigate cytotoxicity. Our results indicated that the YAG:Nd³⁺ fibers possessed a fine, irregularly porous fibrous morphology with an average diameter of 378 nm. The florescence of the sample (1064 nm) could be excited over a wide wavelength range in the NIR region. During the release process of IBU in simulated body fluid (SBF), along with the dissolving of the drug, the solvent entered into the pores, and the emission intensity of the YAG:Nd³⁺ fibers at 1064 nm decreased gradually, owing to a quenching effect of the hydroxy groups, thus provided an approach to track and monitor drug release. In addition, cytotoxicity investigations revealed that these YAG:Nd³⁺ fibers were biocompatible with human cells. Consequently, the porous YAG:Nd³⁺ fibers are a promising material for applications as advanced drug carriers.     

Luminescence functionalization of SBA-15 by YVO4:Eu3+ as a novel drug delivery system

Luminescence functionalization of the ordered mesoporous SBA-15 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process, resulting in the formation of the YVO4:Eu3+@SBA-15 composite material. This material, which combines the mesoporous structure of SBA-15 and the strong red luminescence property of YVO4:Eu3+, can be used as a novel functional drug delivery system. The structure, morphology, porosity, and optical properties of the materials were well characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, N2 adsorption, and photoluminescence spectra. As expected, the pore volume, surface area, and pore size of SBA-15 decrease in sequence after deposition of the YVO4:Eu3+ layer and the adsorption of ibuprofen (IBU, drug). The IBU-loaded YVO4:Eu3+@SBA-15 system still shows the red emission of Eu3+ (617 nm, 5D0-7F2) under UV irradiation and the controlled drug release property. Additionally, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU in the system, making the extent of drug release easily identifiable, trackable, and monitorable by the change of luminescence. The system has great potential in the drug delivery and disease therapy fields.     

Mesoporous silica functionalized with an AIE luminogen for drug delivery

An aggregation-induced emission (AIE) luminogen, tetraphenylethene, has been successfully grafted onto mesoporous silica SBA-15 for the first time. The materials emit blue light upon UV irradiation, and are photostable for the ibuprofen (IBU) drug loading and release process, indicating their great potential for biomedical applications.     

Preparation and physicochemical properties of konjac glucomannan ibuprofen ester as a polysaccharide-drug conjugate

Abstract

A novel drug-polysaccharide conjugate with konjac glucomannan (KGM) as a drug carrier was fabricated through the esterification of ibuprofen (IBU), an anti-inflammatory drug, with KGM. The influences of the reaction conditions, such as the amount of ibuprofen acryl chloride, reaction time, reaction temperature, and the amount of catalyst, on the degree of substitution were investigated. KGM ibuprofen ester (KGM-IBU) was characterized by Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD), solid-state ¹³C NMR, scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). The hydrophobic structure of IBU in KGM-IBU was proven by the fluorescence emission spectra of pyrene. In addition, by using commercially available ibuprofen sustained-release capsules (IBU-SRC) as a control, the in vitro controlled release performance of KGM-IBU was evaluated. The cumulative release of IBU-SRC within 36?h was 94%, while that of KGM-IBU within 36?h was 77%. The results showed that KGM-IBU had better sustained-release performance without a burst release effect. The obtained products could be used as a potential biocompatible sustained-release drug delivery system.     

Gd2O3:Eu@mSiO2核壳双功能纳米棒的制备及性质

通过水热法和正硅酸乙酯水解法制备了一种新颖的Gd2O3:Eu@mSiO2核壳双功能(荧光和介孔)纳米棒。用扫描电镜(SEM)、透射电镜(TEM)、X射线粉末衍射(XRD)、红外光谱(FTIR)等多种测试手段对样品的形貌、物相结构进行分析表征。结果表明,该核壳结构纳米材料以Gd2O3:Eu纳米棒(长~400 nm,直径~100 nm)为核,介孔SiO2为壳,尺寸均匀,分散性良好。荧光光谱表明,在紫外光激发下,核壳纳米棒发射强烈的橙红色荧光。同时该核壳纳米棒能成功标记NCI-H460肺癌细胞。以布洛芬(IBU)为药物模型研究核壳纳米棒的药物负载和释放行为,结果表明,Gd2O3:Eu@mSiO2核壳纳米棒对IBU的负载量可达10.25%,而且其具有明显的缓释效果。IBU负载的样品(IBU-Gd2O3:Eu3+@mSiO2)在紫外光照射下仍呈现Eu3+的橙红色发光,且Eu3+在载药系统中的发光强度随IBU释放量的变化而变化,因此通过发光强度的变化可以跟踪和监测药物及其释放情况。     

co-Condensation Synthesis of Salicylaldimine Calcium Complex Containing Mesoporous Silica Nanoparticles as Carriers for Drug Release

A series of functional mesoporous silica nanoparticles（MSNs） was synthesized by a one-step simple synthesis approach involving co-condensation of tetraethoxysilane（TEOS） and salicylaldimine ligand（Sal-Si） in the presence of cetyltrimethylammonium chloride（CTAC） under basic conditions.The target MSNs with different sizes （50,100 and 200 nm,respectively） were obtained.Furthermore,the Ca^2＋ cations were also introduced into MSNs.The prepared nanoparticles were characterized by means of infrared（IR） spectra,thermogravimetric analysis（TGA）,inductively coupled plasma（ICP）,CHN elemental analysis,nitrogen adsorption-desorption,scanning electron microscope（SEM） and transmission electron microscope（TEM）.Ibuprofen（IBU） which contains carboxyl groups was selected as a model drug.The results of drug loading and release reveal that the loading capacities and release behaviors of the model drug are highly dependent on the Ca^2＋ cations in MSNs.The release of IBU from the MSNs functionalized by Ca^2＋ cations is found to be effectively controlled when compared to the release from the MSNs without the functionalization of Ca^2＋ cations,which is due to the ionic interaction between carboxyl groups in IBU and Ca^2＋ cations in MSNs.     

Uniform and size-tunable mesoporous silica with fibrous morphology for drug delivery

A family of mesoporous silica microspheres with fibrous morphology and different particle sizes ranging from about 400 to 900 nm has been successfully synthesized through a facile self-assembly process. The structural, morphological, and textural properties of the samples were well characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), N(2) adsorption/desorption, and thermal gravimetry (TG). The results reveal that this silica-based mesoporous material exhibits excellent physical properties, including a fibrous spherical morphology, good thermal stability, large pore volume, high specific surface area and narrow size distribution. Additionally, the size and textural properties can be tuned by altering the silica precursor/template molar ratio. The formation and the self-assembly evolution process have also been proposed. The obtained materials were further used as a drug delivery carrier to investigate the in vitro drug release properties using doxorubicin (DOX) as a representative model drug. It was found that this kind of silica exhibits good biocompatibility and obvious sustained drug release properties, suggesting its potential application in biological fields.     

Control of Drug Release through the In Situ Assembly of Stimuli‐Responsive Ordered Mesoporous Silica with Magnetic Particles

A site‐selective controlled delivery system for controlled drug release is fabricated through the in situ assembly of stimuli‐responsive ordered SBA‐15 and magnetic particles. This approach is based on the formation of ordered mesoporous silica with magnetic particles formed from Fe(CO)₅ via the surfactant‐template sol‐gel method and control of transport through polymerization of N‐isopropyl acrylamide inside the pores. Hydrophobic Fe(CO)₅ acts as a swelling agent as well as being the source of the magnetic particles. The obtained system demonstrates a high pore diameter (7.1 nm) and pore volume (0.41 cm³ g^?1), which improves drug storage for relatively large molecules. Controlled drug release through the porous network is demonstrated by measuring the uptake and release of ibuprofen (IBU). The delivery system displays a high IBU storage capacity of 71.5 wt %, which is almost twice as large as the highest value based on SBA‐15 ever reported. In vitro testing of IBU loading and release exhibits a pronounced transition at around 32 °C, indicating a typical thermosensitive controlled release.     

Room-temperature metal-activator-free phosphorescence from mesoporous silica

Room-temperature phosphorescence has been observed and studied on metal-activator-free mesoporous silica. The mesoporous silica was prepared using a nonionic triblock copolymer as the mesostructure-directing agent. The as-calcined products have a well-ordered porous structure and exhibit strong phosphorescence under ultraviolet light excitation. The luminescence spectra are featured with several peaks in the visible region. The luminescence intensity is found to vary as a function of the calcination temperature and reach a maximum around 500-600 °C, but the peak positions remain nearly unchanged. The average luminescence lifetime is several hundred microseconds, and the luminescence can persist for seconds after the excitation is switched off. In addition, due to the moderate calcination temperature, phosphorescent mesoporous silica monoliths with controllable sizes and shapes have been fabricated. Such mesoporous silica materials, including both powders and monoliths, with strong phosphorescence could find promising applications as low-density and eco-friendly phosphors and optically detectable drug carriers.     

pH-sensitive polyelectrolyte complex gel microspheres composed of chitosan/sodium tripolyphosphate/dextran sulfate: swelling kinetics and drug delivery properties

Porous chitosan (CS) polyelectrolyte complex (PEC) hydrogel microspheres were prepared via either wet phase-inversion or ionotropic crosslinking with sodium tripolyphosphate (Na+ - TPP) and dextran sulfate (DS). The resulting microspheres were characterized using scanning electron microscopy (SEM) and elemental analysis (EA). The controlled release behavior of ibuprofen (IBU) from these microspheres was investigated. The PEC microspheres were about 700-950 microm in diameter with large pores and open porous structure. The CS/TPP/DS microspheres resisted hydrolysis in strong acid and biodegradation in enzymatic surroundings. The swelling kinetics for CS microspheres was close to Fickian diffusion, whereas those for CS/TPP and CS/TPP/DS were non-Fickian. Furthermore, the equilibrium water content (EWC) and water diffusion coefficient (D) increased with the pH of the media. The release profiles of IBU from CS/TPP/DS microspheres were slow in simulated gastric fluid (SGF, pH 1.4) over 3 h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 6 h after changing media. Overall the results demonstrated that CS/TPP/DS microspheres could successfully deliver a hydrophobic drug to the intestine without losing the drug in the stomach, and hence could be potential candidates as an orally administered drug delivery system.     

Preparation and drug release behavior of temperature-responsive mesoporous carbons

A temperature-responsive composite based on poly (N-isopropylacrylamide) (PNIPAAm) and ordered mesoporous carbons (OMCs) has been successfully prepared by a simple wetness impregnation technique. The structures and properties of the composite were characterized by infrared spectroscopy (IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), N₂ sorption, thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The results showed that the inclusion of PNIPAAm had not greatly changed the basic ordered pore structure of the OMCs. Ibuprofen (IBU) was selected as model drug, and in vitro test of IBU release exhibited a temperature-responsive controlled release delivery.     

Rattle-type hollow CaWO4:Tb(3+)@SiO2 nanocapsules as carriers for drug delivery

Rattle-type hollow nanocapsules are among of the most promising candidates as drug carriers owing to their huge inner space and multifunctional material combination. In this paper, rattle-type hollow CaWO(4):Tb(3+)@SiO(2) nanocapsules with a diameter of 100-110 nm and a wall thickness around 10 nm were fabricated. The hollow silica nanospheres were used as nano-reactors and the luminescent core of CaWO(4):Tb(3+) was post-filled into the nano-reactors by a vacuum nano-casting route combined with a Pechini-type sol-gel method. Subsequently, doxorubicin hydrochloride (DOX), a model of an anti-cancer drug, is loaded into the CaWO(4):Tb(3+)@SiO(2) nanocapsules and their cell cytotoxicity, cancer cell uptake and drug release behavior are investigated in vitro. The prepared multifunctional inorganic nanocapsules show a loading capacity for DOX as high as 124 mg g(-1) and sustained-release properties. The release profile of the drug from DOX-loaded nanocapsules can last over five days. Besides, the blank CaWO(4):Tb(3+)@SiO(2) shows very low cytotoxicity against cancer cell lines (HeLa cell) while the DOX-loaded nanocapsules exhibit relatively high efficiency for killing of HeLa cells. The rapid cancer cell uptake process is observed by confocal laser scanning microscopy. The results indicate that a rattle-type hollow CaWO(4):Tb(3+)@SiO(2) nanocapsule has the potential to be used as drug carrier in therapy. Moreover, it is possible to extend the synthetic strategy in this study to other rattle-type multifunctional composites to meet various demands.     

Facile synthesis of blue-emitting carbon dots@mesoporous silica composite spheres

This paper reported a facile and effective approach towards high-efficient composite luminophores by embedding blue-emitting N-doped carbon dots into spherical SiO₂ matrix (CDs@SiO₂). Mesoporous silica microspheres (r-CDs@MSN) with strong luminescence were synthesized by removing CTAB templates in CDs@SiO₂ using reflux with acetone. The r-CDs@MSN possess a spherical morphology with smooth surface and a diameter of 130 nm, while it exhibits an excitation-independent blue emission peak at 440 nm with an internal quantum yield of 21.5%. BET result shows that the corresponding surface area and adsorption total pore volume are 156.27 m²/g and 0.682 cm³/g, which is suitable for the drugs loading and release. The results indicate that r-CDs@MSN might act as a potential fluorescent drug carrier.     

A luminescent and mesoporous core-shell structured Gd2O3 : Eu(3+)@nSiO2@mSiO2 nanocomposite as a drug carrier

In this paper, Gd(2)O(3) : Eu(3+) nanospheres have been encapsulated with nonporous silica and further layer of ordered mesoporous silica through a simple sol-gel process. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N(2) adsorption/desorption, photoluminescence (PL) spectra, and kinetic decay were used to characterize the sample. The results indicate that the nanocomposite with general 50 nm shell thickness and 270 nm core size shows typical ordered mesoporous characteristics (2.4 nm) and has spherical morphology with a smooth surface and narrow size distribution. Additionally, the obtained inorganic nanocomposite shows the characteristic emission of Eu(3+) ((5)D(0)→(7)F(1-4)) even after the loading of drug molecules. The biocompatibility test on L929 fibroblast cells using MTT assay reveals low cytotoxicity of the system. Most importantly, the nanocomposite can be used as an effective drug delivery carrier. A typical anticancer drug, doxorubicin hydrochloride (DOX), was used for drug loading, and the DOX release, cytotoxicity, uptake behavior and therapeutic effects were examined. It was found that DOX is shuttled into the cell by the nanocomposite and released inside cells after endocytosis and that the DOX-loaded nanocomposite exhibited greater cytotoxicity than free DOX. These results indicate that core-shell structured Gd(2)O(3) : Eu(3+)@nSiO(2)@mSiO(2) nanocomposite has potential for drug loading and delivery into cancer cells to induce cell death.     

Preparation and evaluation of Ibuprofen solid dispersion systems with kollidon particles using a pulse combustion dryer system

Solid dispersions (SDs) of ibuprofen (IBU) were prepared with four carriers: Kollidon 25, Kollidon 30, Kollidon VA64, and Kollidon CL, using a newly developed pulse combustion dryer system, HYPULCON. Physicochemical properties of the SDs obtained were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and Fourier transformation IR spectroscopy (FT-IR). Powder X-ray diffraction (PXRD) showed that the crystal diffraction peaks of IBU in SDs disappeared completely, and in differential scanning calorimetry (DSC) curves, the endothermic peaks of IBU in SDs were not observed. Fourier transformation IR spectroscopy (FT-IR) proved that interactions between the drug and carrier existed. These findings demonstrated that IBU changed to an amorphous form in the SDs with the four carriers using the pulse combustion dryer system. The dissolution property of IBU in the SDs was markedly enhanced. The dissolution test showed that after 5 min of dissolution, the concentrations of IBU in the SDs with Kollidon CL as the carrier was 43.81 mug/ml, corresponding to 13.0 times that of pure IBU. So, it is demonstrated that the pulse combustion dryer system is very useful for preparing SDs of IBU with Kollidon of different grades as carriers.     

Preparation and application of mesoporous core-shell nanosilica using leucine derivative as template in effective drug delivery

Core-shell structured mesoporous silica nanoparticles have been firstly synthesized with the new template from L-leucine methyl ester hydrochloride (H-Leu-OMe·HCl). LMSNs were characterized by transmission electron microscopy (TEM), nitrogen adsorption/desorption, and small-angle X-ray diffraction (SAXRD), demonstrating a well-ordered mesostructure. After loading doxorubicin hydrochloride (Dox) into pores, considerable loading capacity of 30.5% and favorable cumulative release amount were obtained. MTT assay suggested that Dox-loaded LMSNs demonstrated great promise to anti-tumor. The use of MSNs with the synthesized template, as a drug delivery carrier, will extend the pharmaceutical applications of silica materials.     

Synthesis, characterization, and in vitro pH-controllable drug release from mesoporous silica spheres with switchable gates

To accomplish pH-controllable drug release on mesoporous carrier, one of the best ways is to graft stimuli-responsive organic molecules around mesopore outlets. In this work, the pH-responsive propyldiethylenetriamine groups (abbreviative phrase: multiamine chains) were grafted around mesopore outlets of mesoporous silica spheres (MSS) and expected to act as pH-responsive gates. To this end, three multiamine-grafted MSS (i.e., NM1, NM2, and NM3) were synthesized under different reaction temperatures and reaction times. The reaction temperature and time for multiamine grafting were 25 °C and 12 h for NM1, 100 °C and 1 h for NM2, and 100 °C and 12 h for NM3, respectively. Through systematic investigations of TEM, SEM, N(2) adsorption/desorption, TG, and (29)Si MAS NMR, it was found that NM3 had the highest grafting amount of multiamine chains. It was further confirmed that the multiamine chains around the pore outlets of NM3 played the role of "molecular switch" that could well control the transport of guest drug molecules. In contrast, the multiamine chains around the pore outlets of NM2 and NM3 did not show gate effect. The difference should be decided by the fact whether the grafting amount of multiamine chains around mesopore outlets were sufficient under determined reaction temperature and time. In the tests of in vitro drug release, multiamine-gated MSS (i.e., NM3) showed highly sensitive response to the solution pH. At high pH (pH 7.5), ibuprofen (IBU) in this carrier released rapidly and completely within 2 h; at low pH (pH 4.0 or 5.0), only a small part of the IBU (13 wt %) was slowly released from this carrier and the most of IBU was effectively confined in mesopores.