pSi Microparticles Research Articles

Dynamic magnesiothermic reduction of various silica to porous silicon structures for lithium battery anodes

A dynamic magnesiothermic reduction (DMR) of various silica having different size and porosity is conducted to study the effects of silica properties on the ⅰ) DMR reaction kinetics, ⅱ) properties of resulting porous silicon (pSi) microparticles, and ⅲ) performances of pSi/C composites as anodes in lithium batteries. A DMR kinetic study using the Ginstling–Brounstein diffusion model shows that the smaller the silica particle size, the higher the reduction rate and the lower the apparent activation energy. Irrespective of silica properties, all the resulting pSi particles have mesoporous structures. The pSi particles comprise interconnected small primary silicon nanoparticles (approximately 30–40 nm in diameter) to render similar particle morphologies to those of the parent silica. Owing to these appealing features of pSi particles, pSi/C composites exhibit excellent cycling performance for over 200 cycles and high rate capabilities, whereas SiMP/C (prepared with a non-porous silicon microparticles) loses most of its capacity in early cycles owing to high resistance build-up during cycling. Overall, the DMR of silica precursors of several micrometers or less in size (preferably porous precursors) are desirable for the production of high-purity pSi microparticles for use in high-capacity and stable anodes for advanced lithium batteries.

Porous silicon microparticles as efficient carriers for immunologic adjuvants

In this work we report a first-time combination of porous silicon (pSi) particles with the immunologic adjuvant Pam3CSK4, a TLR 1/2 agonist, as a tool for immunotherapy. pSi is a sponge-like biocompatible and biodegradable nanomaterial with high porosity, large surface-to-volume ratio and tunable surface, suitable for drug delivery applications. This study provides, by means of live-cell confocal microscopy, an insight about the time course of the interaction of free Pam3CSK4 vs vectorized by pSi microparticles with human dendritic cells (DCs). We found a delay in the ingestion of the agonist when carried by pSi microparticles. These findings were supported by the observation of the morphological changes related to the activation of DCs that occurred with a 5 h difference when treated with the vectorized ligand.These results provide the first demonstration of pSi as a conceivable candidate to deliver Pam3CSK4 to DCs paving the way towards immunotherapy practice.

Reduction kinetics of porous silicon synthesis for lithium battery anodes

Porous silicon (pSi) microparticles can be favorably employed as the high-capacity and stable anode materials in all formats of lithium-based batteries. Magnesiothermic reduction reaction (MRR) of low-cost silica produces pSi structures at relatively low temperatures; however, yield and reduction selectivity are currently limited. Herein, we conduct MRR kinetic studies using the Ginstling–Brounstein (GB) and Jander diffusion models under dynamic (via reactor rotation) and static conditions (D-MRR and S-MRR, respectively) at various reduction temperatures and times. The reduction rate and nominal kinetic constants for the d-MRR are found to be more than three times greater than those for the S-MRR, possibly because of the enhanced mass transfer rate in the d-MRR. d-MRR results in superior precursor conversion and pSi yield than S-MRR. The apparent activation energy for d-MRR is approximately 180 kJ mol–1 by GB model. The pSi microparticles are mesoporous (pore size = 23.7 nm, pore volume = 0.30 cm3 g–1) and comprise interconnected primary silicon nanoparticles (SiNPs) (diameter = 30 nm). Therefore, a pSi/C composite anode demonstrates significantly enhanced cycling stability compared with conventional solid SiNP/C composites. Overall, d-MRR is a highly efficient and scalable production process for pSi microparticles for use in high-capacity anodes for advanced lithium-based batteries.

Trans-Cinnamaldehyde Eluting Porous Silicon Microparticles Mitigate Cariogenic Biofilms

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.

Porous Si Microparticles Infiltrated with Magnetic Nanospheres

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.

Controlling and Predicting the Dissolution Kinetics of Thermally Oxidised Mesoporous Silicon Particles: Towards Improved Drug Delivery

Porous silicon (pSi) continues to receive considerable interest for use in applications ranging from sensors, biological scaffolds, therapeutic delivery systems to theranostics. Critical to all of these applications is pSi degradation and stabilization in biological media. Here we report on progress towards the development of a mechanistic understanding for the dissolution behavior of native (unoxidized) and thermally oxidized (200–600 °C) pSi microparticles. Fourier transform infrared (FTIR) spectroscopy was used to characterize the pSi surface chemistry after thermal oxidation. PSi dissolution was assessed using a USP method II apparatus by monitoring the production of orthosilicic acid, and the influence of gastro-intestinal (GI) fluids were examined. Fitting pSi dissolution kinetics with a sum of the exponential model demonstrated that the dissolution process strongly correlates with the three surface hydride species and their relative reactivity, and was supported by the observed FTIR spectral changes of pSi during dissolution. Finally, the presence of GI proteins was shown to hamper pSi dissolution by adsorption to the pSi surface acting as a barrier preventing water attack. These findings are significant in the optimal design of pSi particles for oral delivery and other controlled drug delivery applications.

Plant-Derived Tandem Drug/Mesoporous Silicon Microcarrier Structures for Anti-Inflammatory Therapy.

The properties of nanostructured plant-derived porous silicon (pSi) microparticles as potential candidates to increase the bioavailability of plant extracts possessing anti-inflammatory activity are described in this work. pSi drug carriers were fabricated using an eco-friendly route from the silicon accumulator plant bamboo (tabasheer) powder by magnesiothermic reduction of plant-derived silica and loaded with ethanolic extracts of Equisetum arvense, another silicon accumulator plant rich in polyphenolic compounds. The anti-inflammatory properties of the active therapeutics present in this extract were measured by sensitive luciferase reporter assays; this active extract was subsequently loaded and released from the pSi matrix, with a clear inhibition of the activity of the inflammatory signaling protein NF-κB over a period of hours in a sustained manner. Our results showed that after loading the extracts of E. arvense into pSi microparticles derived from tabasheer, enhanced anti-inflammatory activity was observed owing to enhanced solubility of the extract.

Porous silicon microcarriers for extended release of metformin: Design, biological evaluation and 3D kinetics modeling

Nanostructured porous silicon microparticles (μPSip) synthesized by electrochemical etching were used as tunable carriers for sustained delivery of metformin hydrochloride (MET), an oral antihyperglycemic agent. The surface of native PSi microparticles was modified by thermal oxidation to enhance μPSip stability and MET physical adsorption. Morphological and physicochemical properties of the porous carrier were characterized by a combination of scanning electron microscopy, nitrogen adsorption–desorption, and zeta potential techniques. Drug loading was confirmed by ATR Fourier transform infrared spectroscopy, and loading efficiency was quantified by thermogravimetric analysis and UV–Vis. From MET released profiles, we demonstrated that thermally oxidized µPSip exhibited a sustained release during 26 h, with burst effect depending on pH of the microenvironment. Native PSi loaded particles showed a complete MET release within 6 h with a substantial burst effect at 1 h. The loading kinetics of MET at different initial concentrations were satisfactorily predicted with a 3D diffusional model based on surface diffusion. The proposed model showed that the surface diffusion coefficient (Ds) values increase exponentially as a function of MET loading. The mass transport parameters obtained from the loading kinetics were used to predict the release kinetics of MET. The comparison of experimental and predicted results showed an accurate representation of the data, highlighting the reliability of the model. Through in vivo studies, it was demonstrated that MET-μPSip microcarriers did not induce inflammatory processes. A sustained hypoglycemic effect was observed for 24 h after composite administration, which is a novel contribution of this work.

Porous silicon-poly(ε-caprolactone) film composites: evaluation of drug release and degradation behavior

This work focuses on an evaluation of novel composites of porous silicon (pSi) with the biocompatible polymer ε-polycaprolactone (PCL) for drug delivery and tissue engineering applications. The degradation behavior of the composites in terms of their morphology along with the effect of pSi on polymer degradation was monitored. PSi particles loaded with the drug camptothecin (CPT) were physically embedded into PCL films formed from electrospun PCL fiber sheets. PSi/PCL composites revealed a release profile of CPT (monitored via fluorescence spectroscopy) in accordance with the Higuchi release model, with significantly lower burst release percentage compared to pSi microparticles alone. Degradation studies of the composites, using gravimetric analysis, differential scanning calorimetry (DSC), and field emission scanning electron microscopy (FESEM), carried out in phosphate-buffered saline (PBS) under simulated physiological conditions, indicated a modest mass loss (15%) over 5weeks due to pSi dissolution and minor polymer hydrolysis. DSC results showed that, relative to PCL-only controls, pSi suppressed crystallization of the polymer film during PBS exposure. This suppression affects the evolution of surface morphology during this exposure that, in turn, influences the degradation behavior of the polymer. The implications of the above properties of these composites as a possible therapeutic device are discussed.

Optical Study of Diamine Coupling on Carboxyl-Functionalized Mesoporous Silicon.

A functionalization strategy, consisting of a silylation reaction by acrylic acid followed by diamine coupling, preserves and stabilizes the photoluminescence (PL) of porous silicon (pSi) microparticles suspended in ethanol. We found that under the condition of efficient amine coupling, besides the orange emission typical of the native pSi, an emission band in the blue region appears. The investigation of the interaction between pSi and diamine shows that diamine quenches and shifts the orange band meanwhile it induces an increase of the intensity of the blue one. PL lifetimes of the orange and blue bands are in the micro and nano second range, respectively. These values and their wavelength dependence clearly prove that the two bands have different origin: quantum confinement and nitrogen impurities introduced at silicon/silicon oxide interface, respectively. Thus, they can be used to discriminate between the pSi microparticles obtained by silylation, which expose carboxylic groups and the pSi microparticles after the diamine coupling, which bear amine functionalities at the surface. The increase in the stability of the PL emission of pSi in aqueous solution after functionalization, with quantum yields of the order of 1–2%, supports the use in biological systems of these brightly emitting, largely porous microparticles, bearing positive or negative surface charge.

Silencing of Tumor Necrosis Factor Receptor-1 in Human Lung Microvascular Endothelial Cells Using Particle Platforms for siRNA Delivery.

Acute lung injury (ALI) and its most severe manifestation, acute respiratory distress syndrome (ARDS), is a clinical syndrome defined by acute hypoxemic respiratory failure and bilateral pulmonary infiltrates consistent with edema. In-hospital mortality is 38.5% for AL, and 41.1% for ARDS. Activation of alveolar macrophages in the donor lung causes the release of pro-inflammatory chemokines and cytokines, such as TNF-α. To determine the relevance of TNF-α in disrupting bronchial endothelial cell function, we stimulated human THP-1 macrophages with lipopolysaccharide (LPS) and used the resulting cytokine-supplemented media to disrupt normal endothelial cell functions. Endothelial tube formation was disrupted in the presence of LPS-activated THP- 1 conditioned media, with reversal of the effect occurring in the presence of 0.1µg/ml Enbrel, indicating that TNF-α was the major serum component inhibiting endothelial tube formation. To facilitate lung conditioning, we tested liposomal and porous silicon (pSi) delivery systems for their ability to selectively silence TNFR1 using siRNA technology. Of the three types of liposomes tested, only cationic liposomes had substantial endothelial uptake, with human cells taking up 10-fold more liposomes than their pig counterparts; however, non-specific cellular activation prohibited their use as immunosuppressive agents. On the other hand, pSi microparticles enabled the accumulation of large amounts of siRNA in endothelial cells compared to standard transfection with Lipofectamine(®) LTX, in the absence of non-specific activation of endothelia. Silencing of TNFR1 decreased TNF-α mediated inhibition of endothelial tube formation, as well as TNF-α-induced upregulation of ICAM-1, VCAM, and E-selection in human lung microvascular endothelial cells.

A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye

Dysfunction of corneal epithelial stem cells can result in painful and blinding disease of the ocular surface. In such cases, treatment may involve transfer of growth factor and normal adult stem cells to the ocular surface. Our purpose was to develop an implantable scaffold for the delivery of drugs and cells to the ocular surface. We examined the potential of novel composite biomaterials fabricated from electrospun polycaprolactone (PCL) fibres into which nanostructured porous silicon (pSi) microparticles of varying sizes (150–250 μm or <40 μm) had been pressed. The PCL fabric provided a flexible support for mammalian cells, whereas the embedded pSi provided a substantial surface area for efficient delivery of adsorbed drugs and growth factors. Measurements of tensile strength of these composites revealed that the pSi did not strongly influence the mechanical properties of the polymer microfiber component for the Si loadings evaluated. Human lens epithelial cells (SRA01/04) attached to the composite materials, and exhibited enhanced attachment and growth when the materials were coated with foetal bovine serum. To examine the ability of the materials to deliver a small-drug payload, pSi microparticles were loaded with fluorescein diacetate prior to cell attachment. After 6 hours (h), cells exhibited intracellular fluorescence, indicative of transfer of the fluorescein diacetate into viable cells and its subsequent enzymatic conversion to fluorescein. To investigate loading of large-molecule biologics, murine BALB/c 3T3 cells, responsive to epidermal growth factor, insulin and transferrin, were seeded on composite materials. The cells showed significantly more proliferation at 48 h when seeded on composites loaded with these biologics, than on unloaded composites. No cell proliferation was observed on PCL alone, indicating the biologics had loaded into the pSi microparticles. Drug release, measured by ELISA for insulin, indicated a burst followed by a slower, continuous release over six days. When implanted under the rat conjunctiva, the most promising composite material did not cause significant neovascularization but did elicit a macrophage and mild foreign body response. These novel pressed pSi–PCL materials have potential for delivery of both small and large drugs that can be released in active form, and can support the growth of mammalian cells.

Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles.

There is an unmet clinical need to increase lung transplant successes, patient satisfaction and to improve mortality rates. We offer the development of a nanovector-based solution that will reduce the incidence of lung ischemic reperfusion injury (IRI) leading to graft organ failure through the successful ex vivo treatment of the lung prior to transplantation. The innovation is in the integrated application of our novel porous silicon (pSi) microparticles carrying adeno-associated virus (AAV) nanoparticles, and the use of our ex vivo lung perfusion/ventilation system for the modulation of pro-inflammatory cytokines initiated by ischemic pulmonary conditions prior to organ transplant that often lead to complications. Gene delivery of anti-inflammatory agents to combat the inflammatory cascade may be a promising approach to prevent IRI following lung transplantation. The rationale for the device is that the microparticle will deliver a large payload of virus to cells and serve to protect the AAV from immune recognition. The microparticle-nanoparticle hybrid device was tested both in vitro on cell monolayers and ex vivo using either porcine venous tissue or a pig lung transplantation model, which recapitulates pulmonary IRI that occurs clinically post-transplantation. Remarkably, loading AAV vectors into pSi microparticles increases gene delivery to otherwise non-permissive endothelial cells.

Multivalent presentation of MPL by porous silicon microparticles favors T helper 1 polarization enhancing the anti-tumor efficacy of doxorubicin nanoliposomes.

Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be functionalized to present pathogen-associated molecular patterns that activate dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi microparticles, in contrast to free MPL, resulted in the induction of local inflammation, reflected in the recruitment of neutrophils, eosinophils and proinflammatory monocytes, and the depletion of resident macrophages and mast cells at the injection site. Injection of microparticle-bound MPL resulted in enhanced secretion of the T helper 1 associated cytokines IFN-γ and TNF-α by peritoneal exudate and lymph node cells in response to secondary stimuli while decreasing the anti-inflammatory cytokine IL-10. MPL-pSi microparticles independently exhibited anti-tumor effects and enhanced tumor suppression by low dose doxorubicin nanoliposomes. Intravascular injection of the MPL-bound microparticles increased serum IL-1β levels, which was blocked by the IL-1 receptor antagonist Anakinra. The microparticles also potentiated tumor infiltration by dendritic cells, cytotoxic T lymphocytes, and F4/80+ macrophages, however, a specific reduction was observed in CD204+ macrophages.

Characterization of Free and Porous Silicon-Encapsulated Superparamagnetic Iron Oxide Nanoparticles as Platforms for the Development of Theranostic Vaccines.

Tracking vaccine components from the site of injection to their destination in lymphatic tissue, and simultaneously monitoring immune effects, sheds light on the influence of vaccine components on particle and immune cell trafficking and therapeutic efficacy. In this study, we create a hybrid particle vaccine platform comprised of porous silicon (pSi) and superparamagnetic iron oxide nanoparticles (SPIONs). The impact of nanoparticle size and mode of presentation on magnetic resonance contrast enhancement are examined. SPION-enhanced relaxivity increased as the core diameter of the nanoparticle increased, while encapsulation of SPIONs within a pSi matrix had only minor effects on T2 and no significant effect on T2* relaxation. Following intravenous injection of single and hybrid particles, there was an increase in negative contrast in the spleen, with changes in contrast being slightly greater for free compared to silicon encapsulated SPIONs. Incubation of bone marrow-derived dendritic cells (BMDC) with pSi microparticles loaded with SPIONs, SIINFEKL peptide, and lipopolysaccharide stimulated immune cell interactions and interferon gamma production in OT-1 TCR transgenic CD8+ T cells. Overall, the hybrid particle platform enabled presentation of a complex payload that was traceable, stimulated functional T cell and BMDC interactions, and resolved in cellular activation of T cells in response to a specific antigen.

Effect of surface chemistry of porous silicon microparticles on glucagon-like peptide-1 (GLP-1) loading, release and biological activity

Recently, mesoporous silicon (PSi) microparticles have been shown to extend the duration of action of peptides, reducing the need for frequent injections. Glucagon-like peptide 1 (GLP-1) is a potential novel treatment for type 2 diabetes. The aim of this study was to evaluate whether GLP-1 loading into PSi microparticles reduce blood glucose levels over an extended period. GLP-1 (pI 5.4) was loaded and released from the negatively charged thermally oxidized (TOPSi, pI 1.8) and thermally carbonized (TCPSi, pI 2.6) PSi microparticles and from the novel positively charged amine modified microparticles, designated as TOPSi-NH2-D (pI 8.8) and TCPSi-NH2-D (pI 8.8), respectively. The adsorption of GLP-1 onto the PSi microparticles could be increased 3-4-fold by changing the PSi surface charge from negative to positive, indicating that the positive surface charge of PSi promoted an electrostatic interaction between the negatively charged peptide. All the GLP-1 loaded PSi microparticles lowered the blood glucose levels after a single s.c. injection but surprisingly, TOPSi-NH2-D and TCPSi-NH2-D were not able to prolong the effect when compared to TOPSi, TCPSi or GLP-1 solution. However, TOPSi-NH2-D and TCPSi-NH2-D microparticles were able to carry improved payloads of active GLP-1 encouraging continuing further attempts to achieve sustained release.

Hydrosilylated Porous Silicon Particles Function as an Intravitreal Drug Delivery System for Daunorubicin

To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR). pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography-electrospray ionization-multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months. The mean pSi particle size was 30×46×15 μm with an average pore size of 15 nm. Drug loading was determined as 22 μg per 1 mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity. Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected.

Abstract B25: Porous silicon microparticles exhibit immunomodulatory effects leading to suppression of tumor growth.

Abstract Nanoparticles, such as polymeric delivery platforms, can exhibit intrinsic immunostimulant properties, dependent on size, charge, surface modification, and composition. To function as effective adjuvants, a balance between immunostimulatory properties and biocompatibility is essential. We have demonstrated that porous silicon (pSi) microparticles are effective delivery vehicles, with uptake by target cell populations. A peritonitis mouse model was used to access early innate immune responses 24 hours following administration of pSi microparticles. C57BL/6 mice were injected intraperitoneally with microparticles of various shapes and sizes and cytokine production and cell infiltration were assessed. pSi microparticles were found to have proinflammatory effects. The microparticles induced significant leukocyte infiltration into the site of injection and elevated IL-1β levels in lavage fluid. As cancer progresses, immune responses become more tolerant and cancer cells become more refractory to chemotherapies. Select chemotherapeutics, including cyclophosphamide, doxorubicin, and paclitaxel, have immunodulatory effects. Based on the immunopotentiating effects of pSi microparticles, and the ability of monophosphoryl lipid A (MPL) adsorbed pSi microparticles to activate antigen presenting cells, we sought to potentiate the doxorubicin-mediated immune response through co-delivery of MPL-pSi microparticles. When tumors in mice bearing intramammary 4T1-luc breast tumors reached a volume of 100 mm3, mice were injected with doxorubicin loaded liposomes (5 mg/kg) and MPL-pSi microparticles (5x108 microparticles; 10 µg MPL equivalent) by means of tail vein injection. Tumor growth was monitored by calipher measurements and luciferase expression using the IVIS Imaging System 200. While MPL-pSi microparticle-treated mice exhibited reduced tumor growth, mice receiving MPL-pSi microparticles and doxorubicin-loaded liposomes exhibited arrest of tumor growth. Thus pSi microparticles are an attractive immunopotentiating platform, with applications for both drug and antigen delivery. Citation Format: Ismail M. Meraz, Laura Williams, Marie Yang, Edward C. Lavelle, Rita E. Serda. Porous silicon microparticles exhibit immunomodulatory effects leading to suppression of tumor growth. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B25.

Porous silicon-based nanostructured microparticles as degradable supports for solid-phase synthesis and release of oligonucleotides

We describe the preparation of several types of porous silicon (pSi) microparticles as supports for the solid-phase synthesis of oligonucleotides. The first of these supports facilitates oligonucleotide release from the nanostructured support during the oligonucleotide deprotection step, while the second type of support is able to withstand the cleavage and deprotection of the oligonucleotides post synthesis and subsequently dissolve at physiological conditions (pH = 7.4, 37°C), slowly releasing the oligonucleotides. Our approach involves the fabrication of pSi microparticles and their functionalisation via hydrosilylation reactions to generate a dimethoxytrityl-protected alcohol on the pSi surface as an initiation point for the synthesis of short oligonucleotides.

Controlled Drug Delivery From Composites of Nanostructured Porous Silicon and Poly( L -Lactide)

Porous silicon (pSi) and poly(L-lactide) (PLLA) both display good biocompatibility and tunable degradation behavior, suggesting that composites of both materials are suitable candidates as biomaterials for localized drug delivery into the human body. The combination of a pliable and soft polymeric material with a hard inorganic porous material of high drug loading capacity may engender improved control over degradation and drug release profiles and be beneficial for the preparation of advanced drug delivery devices and biodegradable implants or scaffolds. In this work, three different pSi and PLLA composite formats were prepared. The first format involved grafting PLLA from pSi films via surface-initiated ring-opening polymerization (pSi-PLLA [grafted]). The second format involved spin coating a PLLA solution onto oxidized pSi films (pSi-PLLA [spin-coated]) and the third format consisted of a melt-cast PLLA monolith containing dispersed pSi microparticles (pSi-PLLA [monoliths]). The surface characterization of these composites was performed via infrared spectroscopy, scanning electron microscopy, atomic force microscopy and water contact angle measurements. The composite materials were loaded with a model cytotoxic drug, camptothecin (CPT). Drug release from the composites was monitored via fluorimetry and the release profiles of CPT showed distinct characteristics for each of the composites studied. In some cases, controlled CPT release was observed for more than 5 days. The PLLA spin coat on pSi and the PLLA monolith containing pSi microparticles both released a CPT payload in accordance with the Higuchi and Ritger-Peppas release models. Composite materials were also brought into contact with human lens epithelial cells to determine the extent of cytotoxicity. We observed that all the CPT containing materials were highly efficient at releasing bioactive CPT, based on the cytotoxicity data.