Incorporation Of Mesoporous Silica Nanoparticles Research Articles

Evaluation of intracellular distribution of folate functionalized silica nanoparticles using fluorescence and hyperspectral enhanced dark field microscopy.

Using nanoparticles as carriers for drug delivery systems has become a widely applied strategy in therapeutics and diagnostics. However, the pattern of their intracellular distribution is yet to be clarified. Here we present an in vitro study on the incorporation of mesoporous silica nanoparticles conjugated with folate and loaded with a cytotoxic drug, Irinotecan. The nanoparticles count and distribution within the cell frame were evaluated by means of enhanced dark field microscopy combined with hyperspectral imagery and 3D reconstructions from double-labeled fluorescent samples. An original post-processing procedure was developed to emphasize the nanoparticles' localization in 3D reconstruction of cellular compartments. By these means, it has been shown that the conjugation of mesoporous silica nanoparticles with folate increases the efficiency of nanoparticles entering the cell and their preferential localization in the close vicinity of the nucleus. As revealed by metabolic viability assays, the nanoparticles functionalized with folate enhance the cytotoxic efficiency of Irinotecan.

Evaluation of the Adsorption Efficiency of Glycine-, Iminodiacetic Acid -, and Amino Propyl-Functionalized Silica Nanoparticles for the Removal of Potentially Toxic Elements from Contaminated Water Solution

In present work, mesoporous silica nanoparticles (MSNs) were prepared with a surface area of 1048 m2g-1 and a large pore size of ca. 6 nm, using Stöber process in the presence of expanding reagent ( n -hexane). The surface of MSNs was modified with three different functional groups (amine, iminodiacetic acid, and glycine) and characterized by a variety of physicochemical techniques. The adsorption studies were carried out at different pH values in two extraction systems. In batch method, the maximum adsorption efficiency of heavy metals was measured to be 95% for all fabricated MSNs at pH 9. At pH 3, the adsorption efficiency of Pb and Cu was observed to be affected by the carboxylic moiety involved in the functional group. As the number of carboxylic moieties increase, the removal efficiency of Pb and Cu ions increased by two folds. The results demonstrated the selectivity of IDA-MSNs for the removal of Pb and Cu ions, even though the multielements are present in an aqueous solution. On the other hand, the incorporation of MSNs into the polymeric membrane showed high water permeability ( 9.96 ± 3 L / m 2 . h . bar ), and 98% rejection was achieved at pH 7 for Cu+2 and Pb+2 ions.

Microfluidic preparation of PLGA composite microspheres with mesoporous silica nanoparticles for finely manipulated drug release.

The current study explored the feasibility of a microfluidic preparation of PLGA composite microspheres with mesoporous silica nanoparticles (MSNs) to finely manipulate the drug release behaviors of the microspheres. MSNs were synthesized via a hydrothermal method, and PLGA microspheres loaded with MSNs (PLGA-MSNs) were prepared using a capillary-based three-phase microfluidic device. Drug loading and release behaviors using rhodamine B (RB) as a water-soluble model drug were investigated and compared with those of PLGA microspheres. MSNs with an average particle size of 119nm, a specific surface area of 902.5cm2/g, and a pore size of approximately 5nm were obtained. The mean diameter of PLGA-MSNs was 56μm (CV=4.91%). A sustained release duration of encapsulated RB from PLGA-MSNs for 4months was achieved without any observable burst release. PLGA microspheres with monodispersion could also allow for a similar release duration of encapsulated RB but encountered a burst release in the mid-term of the studied duration. PLGA-MSNs had a denser outer PLGA layer and a more centralized hollow hole than PLGA microspheres without MSNs. Hence, the incorporation of MSNs into PLGA microspheres via microfluidics could be an efficient strategy to finely tune the drug release behavior of PLGA microspheres.

Preparation and characterization of a three dimensional porous poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles scaffold by low-temperature deposition manufacturing

In this study, we introduced mesoporous silica nanoparticles (MSNs) into poly(lactic-co-glycolic acid) (PLGA) to prepare a novel three dimensional (3D) porous scaffold by low-temperature deposition manufacturing (LDM). During the scaffolds preparing process, LDM managed to fabricate scaffolds with 3D geometry and desirable big pore structures but not damage the bioactivity of biomaterials. In the subsequent freeze-drying process, the as-fabricated scaffolds produced small pore structures due to the phase separation process. The scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectrometer, hydrophilicity, porosity and mechanical test. The mean diameters of big pores were 445 ± 50 μm and 431 ± 32 μm, and those of small pores were 11 ± 3 μm and 8 ± 2 μm for PLGA and PLGA/MSNs scaffolds, respectively. Hydrophilicity examination revealed enhanced hydrophilicity of the composite scaffolds. Besides, the incorporation of MSNs also improves the mechanical property of the composites. Human bone marrow mesenchymal stem cells (hMSCs) were seeded on scaffolds for 3, 5, and 7 days. CCK-8 assay revealed that the introduction of MSNs improved cell proliferation. The adhesion and growth of cells on PLGA/MSNs scaffolds were enhanced over time during culturing period when compared to that on PLGA scaffolds. The results suggested that the 3D-printed PLGA/MSNs scaffolds are promising in cartilage tissue engineering.

Electrospun PLGA membrane incorporated with andrographolide-loaded mesoporous silica nanoparticles for sustained antibacterial wound dressing.

To assess the wound-healing ability of poly(lactic-co-glycolic acid) (PLGA) nanofibrous wound dressing incorporated with andrographolide (Andro)-loaded mesoporous silica nanoparticles (MSNs). PLGA/Andro-MSNs nanofibrous membrane wound dressings were produced by electrospinning. The effects of MSNs on the hydrophilicity, degradation and mechanical strength of membranes were evaluated. The cumulative release of Andro in vitro was obtained. Cell culture and in vivo tests on infectious models were carried out. The PLGA/Andro-MSNs membrane showed a sustained release of Andro. The incorporation of MSNs into PLGA improved the hydrophilicity of the nanofibrous membranes. Cell culture and in vivo tests showed that PLGA/Andro-MSNs membrane can promote epidermal cell adhesion and reduce inflammation process. PLGA/Andro-MSNs nanofibrous membrane exhibited an efficient wound-healing ability.

Mesoporous silica nanoparticles facilitating the dissolution of poorly soluble drugs in orodispersible films

Orodispersible films (ODF) are immediately dissolving/disintegrating intraoral dosage forms, presented as substitutes of conventional tablets or capsules to ease problems associated with swallowing. Efforts have been made to be able to exploit ODFs as dosage forms for poorly soluble drugs. In the last two decades, mesoporous silica nanoparticles (MSNs) have been extensively used in drug delivery applications to overcome solubility problems of drugs. The tunable features of MSNs make them suitable candidates as drug carriers and solubility enhancers. In this study, the feasibility of MSNs as a carrier of poorly soluble drugs, using prednisolone as a model drug, in ODFs was investigated. Our results revealed that the increased amount of MSNs in ODFs leads to shortening of the disintegration time of the films. Drug content investigations showed that low dose ODFs with prednisolone incorporation efficiencies higher than 80% could be produced. Furthermore, the prednisolone release profile from ODFs can be tuned with the incorporation of MSNs as drug carrier (MSNpred). The MSNpred incorporated ODFs yield with immediate release of drug from the ODF, whereby 90% of the prednisolone content could be released in the first minutes. By modifying the MSNpred design with copolymer surface coating, prednisolone (cop-MSNpred) release can be modulated into a two-step sustained release profile. To sum up, the MSNs platform does not only provide careful low dose incorporation into ODF with high efficiency, but it also aids in tuning the drug release profiles from ODFs.

Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties

Poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical properties as well as in vitro degradation behavior of scaffolds were investigated. The mean diameters of nanofibers were 974±68nm for the pure PLGA scaffolds vs 832±70, 764±80, and 486±64 for the PLGA/gelatin, PLGA/10wt% MSNPs, and the PLGA/gelatin/10wt% MSNPs scaffolds, respectively. The results suggested that the incorporation of gelatin and MSNPs into PLGA-based scaffolds enhances the hydrophilicity of scaffolds due to an increase of hydrophilic functional groups on the surface of nanofibers. With porosity examination, it was concluded that the incorporation of MSNPs and gelatin decrease the porosity of scaffolds. Nanoparticles also improved the tensile mechanical properties of scaffolds. Using in vitro degradation analysis, it was shown that the addition of nanoparticles to the nanofibers matrix increases the weight loss percentage of PLGA-based samples, whereas it decreases the weight loss percentage in the PLGA/gelatin composites. Cultivation of rat pheochromocytoma cell line (PC12), as precursor cells of dopaminergic neural cells, on the scaffolds demonstrated that the introduction of MSNPs into PLGA and PLGA/gelatin matrix leads to improved cell attachment and proliferation and enhances cellular processes.

Sustained release of MCP-1 from an electrospun scaffold by incorporation of mesoporous silica nanoparticles

Event Abstract Back to Event Sustained release of MCP-1 from an electrospun scaffold by incorporation of mesoporous silica nanoparticles Shraddha Thakkar1, 2, Oliver Wiltschka3, Patricia Dankers1, 4, Carlijn Bouten1, 2, Mika Linden3 and Cecilia Sahlgren1, 2 1 Eindhoven University of Technology, Institute for Complex Molecular Systems, Netherlands 2 Eindhoven University of Technology, Department of Biomedical Engineering, Soft Tissue Biomechanics & Tissue Engineering, Netherlands 3 University of Ulm, Institute for Inorganic Chemistry II, Germany 4 Eindhoven University of Technology, Department of Biomedical Engineering, Laboratory of Chemical Biology, Netherlands In-situ tissue engineering is an emerging approach that relies on the regenerative capacity of the body to create living tissues at the site of implantation of a scaffold. The implanted scaffold will trigger an immune response, which can be modulated by incorporating bioactive moieties in the scaffold[1] . It is envisioned that a sustained release of cytokine moieties, such as monocyte chemoattracant protein-1 (MCP-1), guide recruitment of cells and improved tissue regeneration. In this study, electrospun scaffolds were fabricated with bisurea-modified polycaprolactone (PCL-BU)[2]. To achieve sustained release from the scaffolds we incorporated mesoporous silica nanoparticles (MSNs), which have a high drug carrying potential, in the scaffold and subsequently loaded the MSNs-PCL-BU scaffold with MCP-1[3]. Fibrous scaffolds were fabricated by electrospinning PCL-BU (provided by SyMO-Chem) in chloroform:methanol (w/w 85:15). The fiber diameter was determined to 5.1 ± 0.33µm by scanning electron microscopy (SEM)(Fig. 1). Aminopropyl functionalized MSNs were synthesised as previously described[4]. SEM verified homogenous morphology and a size distribution of 350 ± 0.40 nm (Fig. 1). The size distribution was further verified by transmission electron microscopy (TEM) and pore size was determined to 3 nm by nitrogen sorption (data not shown). MSN were incorporated in the scaffold by drop casting. MSNs resuspended in ethanol attached onto the scaffold by physisorption, at a concentration of 1mg/50µL, followed by ethanol evaporation. MCP-1 was subsequently loaded to the MSNs-scaffold by adding 300 ng/mL MCP-1 in PBS, onto the scaffold, followed by rinsing in PBS. PCL -BU scaffolds (bare), PCL-BU scaffolds with MSNs without MCP-1 and medium with MCP-1 were used as controls for this study. All scaffolds were incubated in medium and the concentration of MCP-1 released in the medium was measured by enzyme-linked immunosorbent assay (ELISA). Media was collected at 1hr, 4hrs, 24hrs, 3 days, 5 days and 7 days. The bioactivity of the released MCP-1 was evaluated by migration of peripheral blood mononuclear cell (hPBMCs) towards the scaffolds in a Boyden chamber, and the presence of cells on scaffolds was accessed by staining of the cell nuclei (DAPI). MCP-1 is expected to be released in medium through a slow diffusion from MSNs. A net cumulative release of 16ng MCP-1 untill 7 days was observed (Fig. 2) . The MSN-scaffold incorporated with MCP-1 exhibited an initial burst release within the first hour followed by a sustained release of MCP-1 for a week. Migration of cells towards, the scaffolds confirms the release of active MCP-1. The presence of the cells in the scaffolds was shown by DAPI staining (Fig. 3). In conclusion: we showed that a desired prolonged release of MCP-1 can be achieved by loading MCP-1 into MSNs incorporated in electrospun PCL-BU scaffolds. This MSN-scaffold may also be extended to serve as a reservoir for sustained release of other cytokines. The Netherlands Institute for Regenerative Medicine (NIRM)