Three-Dimensional Macroporous Alginate Scaffolds Embedded with Akaganeite Nanorods for the Filter-Based High-Speed Preparation of Arsenic-Free Drinking Water

Separation of arsenic from water is an urgent worldwide issue because of its serious toxic effect on human health and aquatic life. In this study, a filter device composed of three-dimensional (3D) macroporous alginate/akaganeite composite (MAAC) scaffolds is proposed for the convenient separation of arsenic from contaminated water. Akaganeite nanorods with superior arsenic adsorption capability are incorporated and distributed within the macroporous alginate scaffold, without significant aggregation. The micron-sized pores and oxygen functional groups in the MAAC scaffold offer enhanced mass transport of the contaminated water throughout the scaffold without the need for input of any force and allow easy contact of arsenic with the active adsorption sites of the scaffold. The high mechanical strength of the MAAC facilitates structural stability of the materials in aqueous solutions. Moreover, the scaffold is capable of excellent arsenic adsorption and can reduce the concentration of arsenic in contaminated water to the acceptable drinking-water level (10 μg L^–1). We also demonstrate that a column filter device constructed by stacking several MAAC scaffolds enables a continuous supply of drinking water with a permissible limit of arsenic according to the World Health Organization in a high-purification speed (∼22–25 mL min^–1 under gravity), which could potentially provide an appropriate technology to obtain arsenic-free drinking water in developing countries

Extra-Large Pore Mesoporous Silica Nanoparticles Enabling Co-Delivery of High Amounts of Protein Antigen and Toll-like Receptor 9 Agonist for Enhanced Cancer Vaccine Efficacy

Cancer vaccine aims to invoke antitumor adaptive immune responses to detect and eliminate tumors. However, the current dendritic cells (DCs)-based cancer vaccines have several limitations that are mostly derived from the <i>ex vivo</i> culture of patient DCs. To circumvent the limitations, direct activation and maturation of host DCs using antigen-carrying materials, without the need for isolation of DCs from patients, are required. In this study, we demonstrate the synthesis of extra-large pore mesoporous silica nanoparticles (XL-MSNs) and their use as a prophylactic cancer vaccine through the delivery of cancer antigen and danger signal to host DCs in the draining lymph nodes. Extra-large pores of approximately 25 nm and additional surface modification of XL-MSNs resulted in significantly higher loading of antigen protein and toll-like receptor 9 (TLR9) agonist compared with conventional small-pore MSNs. <i>In vitro</i> study showed the enhanced activation and antigen presentation of DCs and increased secretion of proinflammatory cytokines. <i>In vivo</i> study demonstrated efficient targeting of XL-MSNs co-delivering antigen and TLR9 agonist to draining lymph nodes, induction of antigen-specific cytotoxic T lymphocytes (CTLs), and suppression of tumor growth after vaccination. Furthermore, significant prevention of tumor growth after tumor rechallenge of the vaccinated tumor-free mice resulted, which was supported by a high level of memory T cells. These findings suggest that mesoporous silica nanoparticles with extra-large pores can be used as an attractive platform for cancer vaccines

Adhesive Composite Hydrogel Patch for Sustained Transdermal Drug Delivery To Treat Atopic Dermatitis

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Continuous administration of steroids often causes undesired side effects; hence, drug delivery systems with high loading capacities and sustained release profiles are required. Herein, adhesive hydrogels for sustained transdermal delivery of dexamethasone (DEX), a potent corticosteroid, have been suggested for AD treatment. The adhesive composite hydrogels comprise a double network of polyacrylamide (PAM) and polydopamine (PDA) embedded with extra-large-pore mesoporous silica nanoparticles (XL-MSNs). The intrinsic skin adhesiveness of the dopamine-derived PAM/PDA hydrogels is further enhanced by XL-MSN incorporation that contributes to the simultaneous enhancement of cohesion and adhesion of the hydrogel. The resulting adhesive hydrogels exhibit a high water content and strong adhesion to porcine skin. A sustained release of DEX is obtained when DEX is loaded within the pores of XL-MSNs in PAM/PDA hydrogels compared to the rapid release from the direct loading of DEX in hydrogels. Application of DEX-loaded MSN@PAM/PDA hydrogels on an AD mouse model led to the significant suppression of AD symptoms, including the restoration of the thickened epidermal layer, decrease in inflammatory cell infiltration in the skin, recovery of collagen deposition, and decreased levels of immunoglobulin E. XL-MSN-embedded adhesive hydrogels could be a potential platform for topical drug delivery to treat inflammatory skin diseases

Sequential Targeted Delivery of Liposomes to Ischemic Tissues by Controlling Blood Vessel Permeability

Delivery systems for therapeutic angiogenesis that deliver angiogenic factors to ischemic tissues have recently been fabricated. However, these systems are designed for surgical implantation or multiple local injections which can cause pain and potential physical burden in patients. Here, we propose a minimally invasive sequential nanoparticle-mediated delivery strategy for ischemic tissue using a murine hindlimb ischemic model. Intravenously injected liposomes that encapsulate VEGF, an angiogenic factor, first target the ischemic sites via the enhanced permeability and retention (EPR) effect in early stages of ischemia. VEGF released from the targeted liposomes maintains the blood vessel permeability for a longer period of time compared to the delivery of empty liposomes. This first nanoparticle-mediated delivery of VEGF to the ischemic site enables extending the temporal window of leaky blood vessel up to 7 days so that the second liposomes could be targeted to the ischemic sites via EPR effect. This strategy will provide opportunities for the targeted delivery of other vessel maturation agents loaded in nanoparticles to ischemic tissue

Effect of Pore Structure of Macroporous Poly(Lactide-<i>co</i>-Glycolide) Scaffolds on the <i>in Vivo</i> Enrichment of Dendritic Cells

The <i>in vivo</i> enrichment of dendritic cells (DCs) in implanted macroporous scaffolds is an emerging strategy to modulate the adaptive immune system. The pore architecture is potentially one of the key factors in controlling enrichment of DCs. However, there have been few studies examining the effects of scaffold pore structure on <i>in vivo</i> DC enrichment. Here we present the effects of surface porosity, pore size, and pore volume of macroporous poly­(lactide-<i>co</i>-glycolide) (PLG) scaffolds encapsulating granulocyte macrophage colony-stimulating factor (GM-CSF), an inflammatory chemoattractant, on the <i>in vivo</i> enrichment of DCs. Although <i>in vitro</i> cell seeding studies using PLG scaffolds without GM-CSF showed higher cell infiltration in scaffolds with higher surface porosity, <i>in vivo</i> results revealed higher DC enrichment in GM-CSF loaded PLG scaffolds with lower surface porosity despite a similar level of GM-CSF released. The diminished compressive modulus of high surface porosity scaffolds compared to low surface porosity scaffolds lead to the significant shrinkage of these scaffolds <i>in vivo,</i> suggesting that the mechanical strength of scaffolds was critical to maintain a porous structure <i>in vivo</i> for accumulating DCs. The pore volume was also found to be important in total number of recruited cells and DCs <i>in vivo.</i> Varying the pore size significantly impacted the total number of cells, but similar numbers of DCs were found as long as the pore size was above 10–32 μm. Collectively, these results suggested that one can modulate <i>in vivo</i> enrichment of DCs by altering the pore architecture and mechanical properties of PLG scaffolds

Bioadhesive Nanoaggregates Based on Polyaspartamide‑<i>g</i>‑C18/DOPA for Wound Healing

Biocompatible adhesive nanoaggregates were synthesized based on polyaspartamide copolymers grafted with octadecylamine (C18) and 3,4-dihydroxyphenylalanine (DOPA), and their adhesive properties were investigated with regard to wound healing. The chemical structure and morphology of the synthesized polyaspartamide-<i>g</i>-C18/DOPA nanoaggregates were analyzed using ¹H-nuclear magnetic resonance spectroscopy (¹H NMR), dynamic light scattering (DLS), and transmission electron microscope (TEM). The in vitro adhesive energy was up to 31.04 J m^–2 for poly­(dimethylacrylamide) gel substrates and 0.1209 MPa for mouse skin, and the in vivo wound breaking strength after 48 h was 1.8291 MPa for C57BL/6 mouse. The MTT assay demonstrated that the synthesized polymeric nanoaggregates were nontoxic. The polyaspartamide-<i>g</i>-C18/DOPA nanoaggregates were <i>in vivo</i> tested to mouse model and demonstrated successful skin adhesion, as the mouse skin was perfectly cured in their dermis within 6 d. As this material has biocompatibility and enough adhesive strength for wound closure, it is expected to be applied as a new type of bioadhesive agent in the human body

Injectable Macroporous Ferrogel Microbeads with a High Structural Stability for Magnetically Actuated Drug Delivery

Macroporous hydrogels are an attractive material platform that can provide shortened interfacial diffusion pathways and high biomacromolecule loading. Recently, macroporous ferrogels have shown high potential for use in the on-demand delivery of bioactive molecules, resulting from their reversible and large volumetric deformation upon magnetic stimulation. However, these macroporous ferrogels require surgical placement in the body due to their large size; an injectable form of macroporous ferrogels has not yet been reported. In this study, injectable macroporous ferrogel microbeads loaded with iron oxide nanoparticles have been prepared on the basis of alginate microbeads for on-demand drug release. A simple solvent exchange and subsequent covalent cross-linking of the alginate chains in hydrogel microbeads induced a high polymer density on the hydrogel network and led to enhanced mechanical properties even after the generation of macropores in the microbeads. The macroporous ferrogel microbeads exhibited good mechanical stability and were stable during needle injection. The increased loading of large biomolecules due to the macroporosity of the microbeads and their large reversible volumetric deformation response to the external magnetic field enabled their potential for use in the on-demand delivery of drugs of assorted sizes by magnetic actuation. As a result of their structural stability, injectable size, and ability for on-demand drug delivery, ferrogel microbeads have promising potential for application in many biomedical fields

Surface Modification with Alginate-Derived Polymers for Stable, Protein-Repellent, Long-Circulating Gold Nanoparticles

Poly(ethylene) glycol is commonly used to stabilize gold nanoparticles (GNPs). In this study, we evaluated the ability of cysteine-functionalized alginate-derived polymers to both provide colloidal stability to GNPs and avoid recognition and sequestration by the body’s defense system. These polymers contain multiple reactive chemical groups (hydroxyl and carboxyl groups) that could allow for ready functionalization with, for example, cell-targeting ligands and therapeutic drugs. We report here that alginate-coupled GNPs demonstrate enhanced stability in comparison with bare citrate-coated GNPs and a similar lack of interaction with proteins <i>in vitro</i> and long <i>in vivo</i> circulation as PEG-coated GNPs

Colloidal Mesoporous Silica Nanoparticles as Strong Adhesives for Hydrogels and Biological Tissues

Sub-100 nm colloidal mesoporous silica (CMS) nanoparticles are evaluated as an adhesive for hydrogels or biological tissues. Because the adhesion energy is proportional to the surface area of the nanoparticles, the CMS nanoparticles could provide a stronger adhesion between two hydrogels than the nonporous silica nanoparticles. In the case of 50 nm CMS nanoparticles with a pore diameter of 6.45 nm, the maximum adhesion energy was approximately 35.0 J/m² at 3.0 wt %, whereas the 10 wt % nonporous silica nanoparticle solution showed only 7.0 J/m². Moreover, the CMS nanoparticle solution had an adhesion energy of 22.0 J/m² at 0.3 wt %, which was 11 times higher than that of the nonporous nanoparticles at the same concentration. Moreover, these CMS nanoparticles are demonstrated for adhering incised skin tissues of mouse, resulting in rapid healing even at a lower nanoparticle concentration. Finally, the CMS nanoparticles had added benefit of quick degradation in biological media because of their porous structure, which may prevent unwanted accumulation in tissues

A Biodegradation Study of SBA-15 Microparticles in Simulated Body Fluid and <i>in Vivo</i>

Mesoporous silica has received considerable attention as a drug delivery vehicle because of its large surface area and large pore volume for loading drugs and large biomolecules. Recently, mesoporous silica microparticles have shown potential as a three-dimensional vaccine platform for modulating dendritic cells via spontaneous assembly of microparticles in a specific region after subcutaneous injection. For further <i>in vivo</i> applications, the biodegradation behavior of mesoporous silica microparticles must be studied and known. Until now, most biodegradation studies have focused on mesoporous silica nanoparticles (MSNs); here, we report the biodegradation of hexagonally ordered mesoporous silica, SBA-15, with micrometer-sized lengths (∼32 μm with a high aspect ratio). The degradation of SBA-15 microparticles was investigated in simulated body fluid (SBF) and in mice by analyzing the structural change over time. SBA-15 microparticles were found to degrade in SBF and <i>in vivo</i>. The erosion of SBA-15 under biological conditions led to a loss of the hysteresis loop in the nitrogen adsorption/desorption isotherm and fingerprint peaks in small-angle X-ray scattering, specifically indicating a degradation of ordered mesoporous structure. Via comparison to previous results of degradation of MSNs in SBF, SBA-15 microparticles degraded faster than MCM-41 nanoparticles presumably because SBA-15 microparticles have a pore size (∼8 nm) and a pore volume larger than those of MCM-41 mesoporous silica. The surface functional groups, the residual amounts of organic templates, and the hydrothermal treatment during the synthesis could affect the rate of degradation of SBA-15. In <i>in vivo</i> testing, previous studies focused on the evaluation of toxicity of mesoporous silica particles in various organs. In contrast, we studied the change in the physical properties of SBA-15 microparticles depending on the duration after subcutaneous injection. The pristine SBA-15 microparticles injected into mice subcutaneously slowly degraded over time and lost ordered structure after 3 days. These findings represent the possible <i>in vivo</i> use of microsized mesoporous silica for drug delivery or vaccine platform after local injection