Magnetic luminescent porous silicon microparticles for localized delivery of molecular drug payloads.
Ontology highlight
ABSTRACT:
SUBMITTER: Gu L
PROVIDER: S-EPMC3033739 | biostudies-literature | 2010 Nov
REPOSITORIES: biostudies-literature
Publications
Magnetic luminescent porous silicon microparticles for localized delivery of molecular drug payloads.
Gu Luo L Park Ji-Ho JH Duong Kim H KH Ruoslahti Erkki E Sailor Michael J MJ
Small (Weinheim an der Bergstrasse, Germany) 20101101 22
Magnetic manipulation, fluorescent tracking, and localized delivery of a drug payload to cancer cells in vitro is demonstrated, using nanostructured porous silicon microparticles as a carrier. The multifunctional microparticles are prepared by electrochemical porosification of a silicon wafer in a hydrofluoric acid-containing electrolyte, followed by removal and fracture of the porous layer into particles using ultrasound. The intrinsically luminescent particles are loaded with superparamagnetic ...[more]
Similar Datasets
Project description:A porous Si (pSi) microparticle-based delivery system is investigated, and the intrinsic luminescence from the particles is employed as a probe to monitor the release of a model protein payload, bovine serum albumin (BSA). The microparticles consist of a core Si skeleton surrounded by a SiO2 shell. Two types of pSi are tested, one with smaller (10 nm) pores and the other with larger (20 nm) pores. The larger pore material yields a higher mass loading of BSA (3 vs 20%). Two different methods are used to load BSA into these nanostructures: the first involves loading by electrostatic physisorption, and the second involves trapping of BSA in the pSi matrix by local precipitation of magnesium silicate. Protein release from the former system is characterized by a burst release, whereas in the latter system, release is controlled by dissolution of the pSi/magnesium silicate matrix. The protein release characteristics are studied under accelerated (0.1 M aqueous KOH, 21 °C) and physiologically relevant (phosphate-buffered saline, pH 7.4, 37 °C) conditions, and the near-infrared photoluminescence signal from the pSi skeleton is monitored as a function of time and correlated with protein release and silicon dissolution. The thickness of the Si core and the SiO2 shell are systematically varied, and it is found that the luminescence signature can be tuned to provide a signal that either scales with protein elution or that changes rapidly near the end of useful life of the delivery system. Although payload release and particle dissolution are not driven by the same mechanism, the correlations between luminescence and payload elution for the various formulations can be used to define design rules for this self-reporting delivery system.
| S-EPMC5951298 | biostudies-literature
Project description:Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles, are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane-nanoneedle interface. In particular, the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largely unexplored. Here, combining state-of-the-art electron and scanning ion conductance microscopy with molecular biology techniques, it is shown that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin-coated pits and caveolae. Nanoneedles enhance the internalization of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae- and clathrin-mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle-mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell-manipulation technologies.
| S-EPMC6606440 | biostudies-literature
Project description:The use of mesoporous silicon particles for drug delivery has been widely explored thanks to their biodegradability and biocompatibility. The ability to tailor the physicochemical properties of porous silicon at the micro- and nanoscale confers versatility to this material. A method for the fabrication of highly reproducible, monodisperse, mesoporous silicon particles with controlled physical characteristics through electrochemical etching of patterned silicon trenches is presented. The particle size is tailored in the micrometer range and pore size in the nanometer range, the shape from tubular to discoidal to hemispherical, and the porosity from 46 to over 80%. In addition, the properties of the porous matrix are correlated with the loading of model nanoparticles (quantum dots) and their three-dimensional arrangement within the matrix is observed by transmission electron microscopy tomography. The methods developed in this study provide effective means to fabricate mesoporous silicon particles according to the principles of rational design for therapeutic vectors and to characterize the distribution of nanoparticles within the porous matrix.
| S-EPMC2920042 | biostudies-literature
Project description:Nanodelivery systems usually improve the biodistribution of drugs, leading to reduced side effects and enhanced therapeutic efficacy. However, only a small portion of the injected nanoparticle dose accumulates in pathological tissue. Challenges in drug delivery arise due to a multitude of transport obstacles in the body, including the endothelium, the extracellular matrix, and the cell membrane. In general, nanoparticles are designed to overcome only a few biological barriers, making them inadequate for localized drug delivery. Accordingly, a multifunctional and multicomponent systems are required to effectively address a wide variety of transport obstacles. A suitable approach to obtain high levels of multifunctionality is to bring together the nanoscale with the microscale, resulting in post-nano strategies for drug delivery. This review discusses several such post-nano approaches, with an emphasis on the multistage vector (MSV) platform. The MSV consists of three components on different spatial scales, each intended to address biological barriers that exist in a specific compartment in the body. The first stage vector is a microparticle that is designed to navigate in the vascular compartment. The second stage vector consists of nanoparticles that are released from the microparticle into the tissue interstitium, where they address biological barriers in extracellular and intracellular compartments. The final component of the system is a small molecule therapeutic agent. A new generation of microparticle-based strategies with expanded applications has recently been developed, including injectable nanoparticle generators and silicon particles for immunotherapy. Notably, the advantage of incorporating microstructures in drug delivery vehicles is apparent from the observation that superior functionality only appears on the microscale, highlighting the inherent functional limitations of nanostructures.
| S-EPMC5489248 | biostudies-literature
Project description:Composite particles made by growing nanoscopic silicon wires from the surface of monodispersed, microsized silica beads were tested in this study for their ability to affect the integrity and permeability of an epithelial cell layer. Polyethylene glycol (PEG) is known to sterically stabilize particles and prevent protein binding; as such, it is a routine way to impart in vivo longevity to drug carriers. The effect of the silica beads, both with and without silicon nanowires and PEG, on the disruption of the tight junctions in Caco-2 cells was evaluated by means of: (a) analysis of the localization of zonula occludens-1 (ZO-1), claudin-1 and f-actin; (b) measurements of trans-epithelial electrical resistance (TEER); (c) real-time quantitative RT-PCR analysis of the expression of PKC-? and PKC-z, which regulate the fluidity of cell membranes, and RhoA and Rac1, which are mainly involved in mechanotransduction processes; and (d) drug permeability experiments with fluorescein-sodium. The results have shown that Si-nanowire-coated silica microparticles added to Caco-2 cells in culture lead to alterations in tight junction permeability and the localization of ZO-1 and f-actin, as well as to decreased width of ZO-1 and claudin-1 at the tight junction and increased expression of PKC transcripts. Si-nanowire-coated silica microparticles increased the permeability of Caco-2 cell monolayers to fluorescein-sodium in proportion to their amount. Effects indicative of loosening the Caco-2 cell monolayers and increasing their permeability were less pronounced for PEGylated particles, owing to their greater supposed inertness in comparison with the non-functionalized beads and nanowires. The analyzed Si-nanowire-coated silica microparticles have thus been shown to affect membrane barrier integrity in vitro, suggesting the possibility of using nanostructured microparticles to enhance drug permeability through the intestinal epithelium in vivo.
| S-EPMC3237727 | biostudies-literature
Project description:An approach for the preparation of an oxidized porous silicon microparticle drug delivery system that can provide efficient trapping and sustained release of various drugs is reported. The method uses the contraction of porous silicon's mesopores, which occurs during oxidation of the silicon matrix, to increase the loading and retention of drugs within the particles. First, a porous Si (pSi) film is prepared by electrochemical etching of p-type silicon with a resistivity of >0.65 Ω cm in a 1:1 (v/v) HF/ethanol electrolyte solution. Under these conditions, the pore walls are sufficiently thin to allow for complete oxidation of the silicon skeleton under mild conditions. The pSi film is then soaked in an aqueous solution containing the drug (cobinamide or rhodamine B test molecules were used in this study) and sodium nitrite. Oxidation of the porous host by nitrite results in a shrinking of the pore openings, which physically traps the drug in the porous matrix. The film is subsequently fractured by ultrasonication into microparticles. Upon comparison with commonly used oxidizing agents for pSi such as water, peroxide, and dimethyl sulfoxide, nitrite is kinetically and thermodynamically sufficient to oxidize the pore walls of the pSi matrix, precluding reductive (by Si) or oxidative (by nitrite) degradation of the drug payload. The drug loading efficiency is significantly increased (by up to 10-fold), and the release rate is significantly prolonged (by 20-fold) relative to control samples in which the drug is loaded by infiltration of pSi particles postoxidation. We find that it is important that the silicon skeleton be completely oxidized to ensure the drug is not reduced or degraded by contact with elemental silicon during the particle dissolution-drug release phase.
| S-EPMC4311935 | biostudies-literature
Project description:Porous silicon (pSi) microparticles obtained by porosification of crystalline silicon wafers have unique optical properties that, together with biodegradability, biocompatibility and absence of immunogenicity, are fundamental characteristics to candidate them as tracers in optical imaging techniques and as drug carriers. In this work, we focus on the possibility to track down the pSi microparticles also by MRI (magnetic resonance imaging), thus realizing a comprehensive tool for theranostic applications, i.e., the combination of therapy and diagnostics. We have developed and tested an easy, quick and low-cost protocol to infiltrate the COOH-functionalized pSi microparticles pores (tens of nanometers about) with magnetic nanospheres (SPIONs-Super Paramagnetic Iron Oxide Nanoparticles, about 5-7 nm) and allow an electrostatic interaction. The structural properties and the elemental composition were investigated by electron microscopy techniques coupled to elemental analysis to demonstrate the effective attachment of the SPIONs along the pores' surface of the pSi microparticles. The magnetic properties were investigated under an external magnetic field to determine the relaxivity properties of the material and resulting in an alteration of the relaxivity of water due to the SPIONs presence, clearly demonstrating the effectiveness of the easy functionalization protocol proposed.
| S-EPMC7153621 | biostudies-literature
Project description:A new and facile approach to selectively functionalize the internal and external surfaces of porous silicon (pSi) for drug delivery applications is reported. To provide a surface that is suitable for sustained drug release of the hydrophobic cancer chemotherapy drug camptothecin (CPT), the internal surfaces of pSi films were first modified with 1-dodecene. To further modify the external surface of the pSi samples, an interlayer was applied by silanization with (3-aminopropyl)triethoxysilane (APTES) following air plasma treatment. In addition, copolymers of N-(2-hydroxypropyl) acrylamide (HPAm) and N-benzophenone acrylamide (BPAm) were grafted onto the external pSi surfaces by spin-coating and UV crosslinking. Each modification step was verified using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, water contact angle (WCA) measurements, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). In order to confirm that the air plasma treatment and silanization step only occurred on the top surface of pSi samples, confocal microscopy was employed after fluorescein isothiocyanate (FITC) conjugation. Drug release studies carried out over 17 h in PBS demonstrated that the modified pSi reservoirs released CPT continuously, while showing excellent stability. Furthermore, protein adsorption and cell attachment studies demonstrated the ability of the graft polymer layer to reduce both significantly. In combination with the biocompatible pSi substrate material, the facile modification strategy described in this study provides access to new multifunctional drug delivery systems (DDS) for applications in cancer therapy.
| S-EPMC6361965 | biostudies-literature
Project description:Despite the wide-spread use of liposomal drug delivery systems, application of these systems for oral purposes is limited due to their large-scale formulation and storage issues. Proliposomes are one of the formulation approaches for achieving solid powders that readily form liposomes upon hydration. In this work, we investigated a dry powder formulation of a model low-soluble drug with phospholipids loaded in porous functionalized calcium carbonate microparticles. We characterized the liposome formation under conditions that mimic the different gastrointestinal stages and studied the factors that influence the dissolution rate of the model drug. The liposomes that formed upon direct contact with the simulated gastric environment had a capacity to directly encapsulate 25% of the drug in situ. The emerged liposomes allowed complete dissolution of the drug within 15 min. We identified a negative correlation between the phospholipid content and the rate of water uptake. This correlation corroborated the results obtained for the rate of dissolution and liposome encapsulation efficiency. This approach allows for the development of solid proliposomal dosage formulations, which can be scaled up with regular processes.
| S-EPMC7465306 | biostudies-literature
Project description:Dental caries, a preventable disease, is caused by highly-adherent, acid-producing biofilms composed of bacteria and yeasts. Current caries-preventive approaches are ineffective in controlling biofilm development. Recent studies demonstrate definite advantages in using natural compounds such as trans-cinnamaldehyde in thwarting biofilm assembly, and yet, the remarkable difficulty in delivering such hydrophobic bioactive molecules prevents further development. To address this critical challenge, we have developed an innovative platform composed of components with a proven track record of safety. We fabricated and thoroughly characterised porous silicon (pSi) microparticles to carry and deliver the natural phenyl propanoid trans-cinnamaldehyde (TC). We investigated its effects on preventing the development of cross-kingdom biofilms (Streptococcus mutans and Candida albicans), typical of dental caries found in children. The prepared pSi microparticles were roughly cubic in structure with 70-75% porosity, to which the TC (pSi-TC) was loaded with about 45% efficiency. The pSi-TC particles exhibited a controlled release of the cargo over a 14-day period. Notably, pSi-TC significantly inhibited biofilms, specifically downregulating the glucan synthesis pathways, leading to reduced adhesion to the substrate. Acid production, a vital virulent trait for caries development, was also hindered by pSi-TC. This pioneering study highlights the potential to develop the novel pSi-TC as a dental caries-preventive material.
| S-EPMC9322055 | biostudies-literature