Synthesis of hollow mesoporous silica (HMS) nanoparticles as a candidate for sulfasalazine drug loading

Hollow mesoporous silica nanoparticles have emerged as attractive drug delivery carriers. In this work, we report successful synthesis of hollow mesoporous silica nanoparticles (HMSNs) using poly tert-butyl acrylate (PtBA) nanospheres as hard templates and CTAB as structure directing agent for loading sulfasalazine into its porous structure. The samples were synthesized using PtBA; sodium dodecyl sulfate (SDS) - in an aqueous solution of CTAB and tetraethylorthosilicate (TEOS) as the inorganic precursor. Two different methods were utilized to remove organic phases including calcination, and acidic/basic ethanolic solvent extraction approach. For the latter, microstructural studies using SEM and N₂ porosimetery revealed the formation of highly uniform mono-dispersed particles of sphere morphology (~ 130 nm) with the high specific surface area (1501 m²/g) and mean pore size of ~ 2.6 nm. However, rather deformed and aggregated sphere-like particles were obtained for the calcined samples. TEM examinations also confirmed the formation of 20–30 nm thick walls for the prepared HMSNs particles. Further, HMSN samples treated by solvent extraction method were functionalized by 3-aminopropyl triethoxysilane (APTS) compound for drug delivery. DTA/TG analysis showed that the total amount of loaded sulfasalazine drug was 5.1 wt%.     

Amorphous silica nanoparticles derived from biowaste via microwave combustion for drug delivery

Amorphous silica nanoparticles are a promising platform for constructing drug delivery vehicles owing to their high biocompatibility and favorable surface chemistry. In the current study, we report the preparation of amorphous silica nanoparticles using rice husk biowaste via easy and rapid microwave-assisted combustion. The obtained results from various characterizations indicate that the prepared sample is an amorphous form of silica nanoparticles having sizes 50–80 nm with high purity. Ciprofloxacin was used as the model drug and it was released from silica nanocarrier in a controlled and prolonged manner. The ciprofloxacin release kinetics was investigated using the Higuchi model and Ritger-Peppas model which corroborate that different process like desorption, diffusion, and surface erosion may be involved in the release of ciprofloxacin from the prepared silica nanocarrier. The antibacterial susceptibility test revealed that the ciprofloxacin loaded silica nanocarrier exhibit a bacterial inhibition zone about 32 ± 4 and 44 ± 3 mm against Escherichia coli and Staphylococcus aureus, respectively. This study can be useful to develop a versatile nanocarrier with controlled delivery of ciprofloxacin to treat different types of bacterial infections.     

Hybrid polymeric systems of mesoporous silica/hydroxyapatite nanoparticles applied as antitumor drug delivery platform

In this study, we report the production of a mesoporous silica/hydroxyapatite-based nanocomposite containing copper (Cu) functionalized with methacrylic acid (MAA), a pH-sensitive polymer. The functionalization of the nanoparticles surface was performed using the microwave method in order to anchor the cross-linking tetraethylene glycol dimethacrylate (TEGDMA), onto the nanoparticles surface followed by MAA polymerization. The materials were characterized by XRD, XRF spectroscopy, scanning and transmission electron microscopy, Fourier transform infrared spectroscopy, thermal analysis, zeta potential, and elemental analysis. Studies of the incorporation and release of the antitumor methotrexate drug were performed in order to evaluate the potential use of these drug carrier systems in cancer therapy. Moreover, the in vitro cytotoxicity of the samples in fibroblast and SAOS-2 cells was investigated, and the activity of the adipose-derived stem cell alkaline phosphatase on nanocomposites was studied by in vitro assays. The results indicate that the Cu-containing nanocomposites can be easily produced and that these compositions have beneficial effects in stem cells, maintaining cell viability, and allowing alkaline phosphatase expression. In conclusion, data from this work show that the nanocomposites obtained have adequate characteristic to be used as drug delivery platform. Furthermore, the biomaterial is a promising structure for treatment of bone tumor.     

Fabrication of porous silica ceramics by gelation-freezing of diatomite slurry

Diatomite-derived porous silica ceramics with high porosities of up to 90% were fabricated using a gelation-freezing method, which resulted in unidirectional cellular or random microstructure with micrometer-sized cells. The ice crystals that were formed during freezing of a diatomite powder dispersed gel were removed by sublimation during vacuum drying, and the green bodies were sintered at 1150–1350 °C for 2 h in air. The thermal conductivity of the porous ceramics prepared with initial solid loadings of 5 and 10 vol% ranged from 0.09 to 0.16 W/(mK) at room temperature. The proposed method is therefore promising for the preparation of ceramic thermal insulators with very low thermal conductivity.     

纳米二氧化硅的制备与表征

本文以正硅酸四乙酯(TEOS)为前驱物,通过溶胶-凝胶法制备了SiO_2纳米粉体。并用FT- IR、SDTA、XRD、TEM表征了所制备的SiO_2纳米粉体的结构和形貌。结果表明SiO_2纳米粒子呈球状,粒径在50～100nm范围内,分布均匀,呈无定形态。     

硅藻土基多孔陶瓷的制备

以硅藻土为主要原料,加入天然有机细粉为造孔剂,水玻璃为高温粘合剂,轻质碳酸钙和轻质碳酸镁为添加剂,经半干压成型,常规烧成,制备出了性能优良的硅藻土多孔陶瓷。随着造孔剂的加入量和烧成制度的改变,制品的气孔率、体积密度和抗压强度等性能也随着改变。     

Surface enhanced fluorescence of anti-tumoral drug emodin adsorbed on silver nanoparticles and loaded on porous silicon

Fluorescence spectra of anti-tumoral drug emodin loaded on nanostructured porous silicon have been recorded. The use of colloidal nanoparticles allowed embedding of the drug without previous porous silicon functionalization and leads to the observation of an enhancement of fluorescence of the drug. Mean pore size of porous silicon matrices was 60 nm, while silver nanoparticles mean diameter was 50 nm. Atmospheric and vacuum conditions at room temperature were used to infiltrate emodin-silver nanoparticles complexes into porous silicon matrices. The drug was loaded after adsorption on metal surface, alone, and bound to bovine serum albumin. Methanol and water were used as solvents. Spectra with 1 μm spatial resolution of cross-section of porous silicon layers were recorded to observe the penetration of the drug. A maximum fluorescence enhancement factor of 24 was obtained when protein was loaded bound to albumin, and atmospheric conditions of inclusion were used. A better penetration was obtained using methanol as solvent when comparing with water. Complexes of emodin remain loaded for 30 days after preparation without an apparent degradation of the drug, although a decrease in the enhancement factor is observed. The study reported here constitutes the basis for designing a new drug delivery system with future applications in medicine and pharmacy.     

A biocompatible drug delivery nanovalve system on the surface of mesoporous nanoparticles

A biocompatible nanovalve attached to the surface of MCM-41 mesoporous nanoparticles is designed to release encapsulated guest molecules controllably under pH activation. This nanovalve system is comprised of α-cyclodextrin (α-CD) rings that encircle p-anisidino linkers, and can be tuned to respond under specific pH conditions through chemical modification of the linkers. One of the distinctive features of this functional nanovalve system lies in its excellent bio-stability and durability in cell culture medium solution, the binding between the α-CD and p-anisidino groups was not interrupted or disintegrated by the proteins in the DMEM solution without adjusting the pH value. Luminescence spectroscopy demonstrates that the on-command pH-activated system displays very good bio-stability—no drug leakage at pH ∼7.4 and excellent drug release performance not only in H₂O but also in cell culture medium at pH ∼5.5.     

Dual responsive block copolymer coated hollow mesoporous silica nanoparticles for glucose-mediated transcutaneous drug delivery

A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein, a glucose-mediated dual-responsive drug delivery system, which combines pH- and H₂O₂-responsive block copolymer grafted hollow mesoporous silica nanoparticles (HMSNs) with microneedle (MN) array patch, has been developed to achieve self-regulated administration. The poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate]-b-poly[2-(dimethylamino)ethyl methacrylate] (PPBEM-b-PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast, the drug release rate is significantly enhanced upon H₂O₂ and pH stimuli due to the chemical change of H₂O₂ sensitive PPBEM block and acid responsive PDM block. Therefore, incorporation of anti-diabetic drug and glucose oxidase (GOx, which can oxidize glucose to gluconic acid and in-situ produce H₂O₂) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both in vitro and in vivo results show this MN device presents a glucose mediated self-regulated drug release characteristic, which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.     

Inorganic nanoparticles as carriers for efficient cellular delivery

Cellular delivery involving the transfer of various drugs and bio-active molecules (peptides, proteins and DNAs, etc.) through the cell membrane into cells has attracted increasing attention because of its importance in medicine and drug delivery. This topic has been extensively reviewed. The direct delivery of drugs and biomolecules, however, is generally inefficient and suffering from problems such as enzymic degradation of DNAs. Therefore, searching for efficient and safe transport vehicles (carriers) to delivery genes or drugs into cells has been challenging yet exciting area of research. In past decades, many carriers have been developed and investigated extensively which can be generally classified into four major groups: viral carriers, organic cationic compounds, recombinant protiens and inorganic nanoparticles. Many inorganic materials, such as calcium phosphate, gold, carbon materials, silicon oxide, iron oxide and layered double hydroxide (LDH), have been studied. Inorganic nanoparticles show low toxicity and promise for controlled delivery properties, thus presenting a new alternative to viral carriers and cationic carriers. Inorganic nanoparticles generally possess versatile properties suitable for cellular delivery, including wide availability, rich functionality, good biocompatibility, potential capability of targeted delivery (e.g. selectively destroying cancer cells but sparing normal tissues) and controlled release of carried drugs. This paper reviews the latest advances in inorganic nanoparticle applications as cellular delivery carriers and highlights some key issues in efficient cellular delivery using inorganic nanoparticles. Critical properties of inorganic nanoparticles, surface functionalisation (modification), uptake of biomolecules, the driving forces for delivery, and release of biomolecules will be reviewed systematically. Selected examples of promising inorganic nanoparticle delivery systems, including gold, fullerences and carbon nanotubes, LDH and various oxide nanoparticles in particular their applications for gene delivery will be discussed. The fundamental understanding of properties of inorganic nanoparticles in relation to cellular delivery efficiency as the most paramount issue will be highlighted.     

Redox and pH dual-responsive biodegradable mesoporous silica nanoparticle as a potential drug carrier for synergistic cancer therapy

Multifunctional mesoporous silica-based nanocarriers able to efficiently encapsulate drugs for stimuli-responsive release and display rapid biodegradation are highly desirable. In this work, we dope disulfide bonds and calcium into silica framework by one step method to obtain a redox and pH dual-responsive biodegradable mesoporous silica nanoparticle (BT-Ca-MSN) as a potential drug carrier for synergistic cancer therapy. TEM and ICP-OES are used to assess the biodegradation behavior of BT-Ca-MSN. The results show that BT-Ca-MSN can significantly biodegrade in a concurrent reductive and acidic environment due to the simultaneous disulfide bonds cleavage and Ca²⁺ release. In addition, BT-Ca-MSN shows efficient drug loading capacity and significant biodegradation-mediated drug release. Moreover, the in-vitro cytotoxicity indicates that BT-Ca-MSN can not only exhibit significant cancer cell killing effect without obvious toxicity on healthy cells via the way of released Ca²⁺-mediated apoptosis, but also can combine with its loaded doxorubicin hydrochloride for synergistic cancer therapy. This work demonstrates that BT-Ca-MSN is a promising platform as drug carrier, providing a paradigm to rationally design biodegradable silica-based carriers for highly efficient cancer therapy.     

Preparation of polymer nanoparticles loaded with doxorubicin for controlled drug delivery

The preparation of polymer nanoparticles loaded with an active principle, commonly used in cancer treatment, is investigated here from the experimental point of view. The main novelty of this work stands in the use of continuous confined impinging jets mixers in combination with realistic materials, notably the biodegradable and biocompatible copolymer poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate) together with two forms of the drug doxorubicin. To our knowledge this is the first attempt to use for such a system a device that can be operated continuously and can be easily scaled up. Nanoparticles are produced via solvent-displacement experimenting different solvents; the effect of the other operating parameters is also investigated. Nanoparticles are characterized in terms of their size distribution and surface properties; for a limited number of samples prepared with the optimized preparation protocol further characterization (in terms of drug loading, incorporation and release profiles) is also carried out. Collected results show that the overall approach is capable of producing nanoparticles with controlled particle size distribution, drug loading and good reproducibility and that on the contrary of what reported in the literature the presence of the active principle does play an important role.     

Responsive polymeric nanoparticles for controlled drug delivery

Small‐molecule drugs often have limited solubility, display rapid clearance or poor selectivity that leads to undesired side‐effects. Although prodrug strategies can improve solubility and lower toxicity, activation ‘on demand’ as well as targeted transport of prodrugs remains a challenge in drug delivery. Responsive polymeric nanoparticles can help meet these challenges with the encapsulation or conjugation of drugs, allowing release at the target site upon triggering by an internal or external stimulus. The adaptable design of polymeric nanoparticles allows them to play a vital role in achieving a specific and desired response following application of a specific stimulus. Here, the most recent progress in responsive polymeric nanoparticles is reviewed with a focus on the chemical properties of the utilized polymers. © 2017 Society of Chemical Industry     

Protein loaded mesoporous silica spheres as a controlled delivery platform

BACKGROUND: The adsorption of bovine serum albumin (BSA) onto mesoporous silica spheres (MPS) synthesized from silica colloids was studied employing real time in situ measurements. The stabilities of the BSA at different pH values, their isoelectric points and zeta potentials were determined in order to probe the interactions between the protein and the mesoporous silica. RESULTS: The pore size of MPS was designed for protein, and this, coupled with an in depth understanding of the physico‐chemical characteristics of the protein and MPS has yielded a better binding capacity and delivery profile. The adsorption isotherm at pH 4.2 fitted the Langmuir model and displayed the highest adsorption capacity (71.43 mg mL^?1 MPS). Furthermore, the delivery rates of BSA from the MPS under physiological conditions were shown to be dependent on the ionic strength of the buffer and protein loading concentration. CONCLUSION: Economics and scale‐up considerations of mesoporous material synthesized via destabilization of colloids by electrolyte indicate the scaleability and commercial viability of this technology as a delivery platform for biopharmaceutical applications. Copyright © 2007 Society of Chemical Industry     

Redox-active silica nanoparticles : Part 2. Photochemical hydrosilylation on a hydride modified silica particle surface for the covalent immobilization of ferrocene

The surface of spherical nonporous monodisperse silica particles (diameter: 200 nm) is covalently modified with hydride by means of hydrosilanization. A direct silicon-carbon link between the hydride modified silica surface and 10-undecylenic acid is obtained by photochemical radical initiated hydrosilylation. A ferrocene unit is attached through an amide link to the carboxylic acid modified surface. Solid-state NMR and DRIFT spectroscopy indicate success of the reactions. The electrochemical oxidation and reduction of the ferrocene modified silica particles are observed after their adsorption on a platinum electrode. The cyclic voltammograms indicate, in addition to the charge transfer between ferrocene units on the particle surface, an interparticle charge transfer.     

Latex‐templated biomineralization of silica nanoparticles with porous shell and their application for drug delivery

A latex‐templating method for synthesizing the core‐shell silica nanoparticles (NPs) with porous shell was developed via biomineralization in the presence of poly[2‐(methacryloyloxy)ethyl] trimethylammonium chloride (pDMC)‐modified polystyrene latex. Calcination of the as‐obtained SiO₂ NPs led to the removal of the latex core and consequently to hollow silica NPs with porous shell. In particularly, the microstructure and thickness of silica shell could be controlled by simply changing the reaction parameters of silicification. Furthermore, facile encapsulation of a drug molecules and its sustained release were demonstrated. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44200.     

基于壳聚糖纳米粒子载药体系的制备与应用研究进展

壳聚糖纳米粒子载药体系因其天然无毒、生物相容性高、可生物降解等特点,在生物医学、化工和食品等领域有广阔的应用前景。本文对制备壳聚糖纳米粒子的离子交联法、聚电解质复合法、乳化交联法、喷雾干燥法和溶剂蒸发法等主要方法进行了综述,并阐述了其制备原理和优缺点。此外,本文结合国内外学者近期的研究工作,综述了壳聚糖纳米粒子载药体系在抗肿瘤药物和抑菌药物方面的应用研究进展,并对壳聚糖装载降糖药物、降脂药物、治疗骨质疏松药物和抗癫痫药物应用进行了简介。最后结合壳聚糖纳米载药体系在制备方法及应用中存在的实际问题,提出多学科研究相结合,开发壳聚糖纳米载药体系的智能控释、靶向递送功能和突破人体特殊生物屏障功能将是其近期的重点研究方向。     

聚多巴胺修饰纳米SiO2颗粒

纳米SiO₂颗粒粒径小、比表面积大,广泛用做填料、涂料、催化剂等。由于纳米SiO₂颗粒表面能高、亲水性强、易团聚、在聚合物基体中的分散性差,需要对其表面修饰改性。多巴胺（DA）分子具有类似贻贝分泌的黏附蛋白的结构单元儿茶酚和活性基团氨基,在碱性条件下,通过氧化自聚可在多种材料表面沉积,形成富含活性基团的聚多巴胺（PDA）包覆层,可进行二次修饰,是近期发展的一种新型表面修饰方法。本文针对纳米SiO₂颗粒表面的PDA功能化修饰,分析了该修饰方法的工艺特点及优势,阐述了SiO₂@PDA纳米颗粒及SiO₂/PDA共聚复合颗粒的制备路线及应用,总结了SiO₂@PDA颗粒表面二次功能化修饰的研究进展。分析表明,SiO₂@PDA表面易于接枝功能化聚合物分子,并可负载功能纳米颗粒,有利于拓展SiO₂纳米颗粒的多功能应用。关于多巴胺与SiO₂纳米颗粒的表面反应机制、沉积动力学、聚合机理等仍需进一步研究。     

Silk fibroin aerogels for drug delivery applications

Silk fibroin (SF) is a natural protein, derived from the Bombyx mori silkworm. Silk fibroin based porous materials are being extensively investigated for biomedical applications, due to their biocompatibility and biodegradability. The results presented here demonstrate the potential of SF aerogels as drug delivery devices for the extended release of ibuprofen, a candidate drug. SF aerogels are loaded with of ibuprofen using supercritical carbon dioxide (scCO₂) at 40 °C and 100 bar. Differential scanning calorimetry of the ibuprofen-loaded SF aerogels indicates that the ibuprofen is amorphous. Scanning electron microscopy and nitrogen adsorption/desorption analysis are used to investigate the morphology and textural properties. Phosphate buffer solution (PBS) soaking studies, at 37 °C and pH 7.4, reveal that SF aerogels do not swell nor exhibit any weight loss for up to 6 h, the lifetime of the release measurements performed in the present study. In vitro ibuprofen release in PBS, at 37 °C and pH 7.4, occurs over a 6-h period when the ibuprofen is loaded in SF aerogel discs that are 1.4 cm in diameter and 0.85 cm in height. In contrast, the dissolution of the same amount of pure ibuprofen occurs in 15 min. Furthermore, the release of ibuprofen from these SF aerogel discs are modeled using the Ritger–Peppas model which indicates that ibuprofen release follows Fickian diffusion.     

pH-responsive drug delivery system based on hollow silicon dioxide micropillars coated with polyelectrolyte multilayers

We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release.