Editorial

3 pages, 161 KiB

Open AccessEditorial

Mesoporous Materials for Drug Delivery and Theranostics

by Valentina Cauda and Giancarlo Canavese

Pharmaceutics 2020, 12(11), 1108; https://doi.org/10.3390/pharmaceutics12111108 - 18 Nov 2020

Cited by 7 | Viewed by 1611

Mesoporous materials, especially those made of silica or silicon, are capturing great interest in the field of nanomedicine [...] Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

Research

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16 pages, 2241 KiB

Open AccessArticle

Silicon Nanofluidic Membrane for Electrostatic Control of Drugs and Analytes Elution

by Nicola Di Trani, Antonia Silvestri, Yu Wang, Danilo Demarchi, Xuewu Liu and Alessandro Grattoni

Pharmaceutics 2020, 12(7), 679; https://doi.org/10.3390/pharmaceutics12070679 - 19 Jul 2020

Cited by 12 | Viewed by 3413

Abstract

Individualized long-term management of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal management of pathologies, such [...] Read more.

Individualized long-term management of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal management of pathologies, such as diabetes, hypertension, rheumatoid arthritis. Several triggered systems for drug delivery have been demonstrated. However, they mostly rely on continuous external stimuli, which hinder their application for long-term treatments. In this work, we investigated a silicon nanofluidic technology that incorporates a gate electrode and examined its ability to achieve reproducible control of drug release. Silicon carbide (SiC) was used to coat the membrane surface, including nanochannels, ensuring biocompatibility and chemical inertness for long-term stability for in vivo deployment. With the application of a small voltage (≤ 3 V DC) to the buried polysilicon electrode, we showed in vitro repeatable modulation of membrane permeability of two model analytes—methotrexate and quantum dots. Methotrexate is a first-line therapeutic approach for rheumatoid arthritis; quantum dots represent multi-functional nanoparticles with broad applicability from bio-labeling to targeted drug delivery. Importantly, SiC coating demonstrated optimal properties as a gate dielectric, which rendered our membrane relevant for multiple applications beyond drug delivery, such as lab on a chip and micro total analysis systems (µTAS). Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

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17 pages, 2512 KiB

Open AccessArticle

Controlled Delivery of Insulin-like Growth Factor-1 from Bioactive Glass-Incorporated Alginate-Poloxamer/Silk Fibroin Hydrogels

by Qing Min, Xiaofeng Yu, Jiaoyan Liu, Yuchen Zhang, Ying Wan and Jiliang Wu

Pharmaceutics 2020, 12(6), 574; https://doi.org/10.3390/pharmaceutics12060574 - 20 Jun 2020

Cited by 14 | Viewed by 2750

Abstract

Thermosensitive alginate–poloxamer (ALG–POL) copolymer with an optimal POL content was synthesized, and it was used to combine with silk fibroin (SF) for building ALG–POL/SF hydrogels with dual network structure. Mesoporous bioactive glass (BG) nanoparticles (NPs) with a high level of mesoporosity and large [...] Read more.

Thermosensitive alginate–poloxamer (ALG–POL) copolymer with an optimal POL content was synthesized, and it was used to combine with silk fibroin (SF) for building ALG–POL/SF hydrogels with dual network structure. Mesoporous bioactive glass (BG) nanoparticles (NPs) with a high level of mesoporosity and large pore size were prepared and they were employed as a vehicle for loading insulin-like growth factor-1 (IGF-1). IGF-1-loaded BG NPs were embedded into ALG–POL/SF hydrogels to achieve the controlled delivery of IGF-1. The resulting IGF-1-loaded BG/ALG–POL/SF gels were found to be injectable with their sol-gel transition near physiological temperature and pH. Rheological measurements showed that BG/ALG–POL/SF gels had their elastic modulus higher than 5kPa with large ratio of elastic modulus to viscous modulus, indicative of their mechanically strong features. The dry BG/ALG–POL/SF gels were seen to be highly porous with well-interconnected pore characteristics. The gels loaded with varied amounts of IGF-1 showed abilities to administer IGF-1 release in approximately linear manners for a few weeks while effectively preserving the bioactivity of encapsulated IGF-1. Results suggest that such constructed BG/ALG–POL/SF gels can function as a promising injectable biomaterial for bone tissue engineering applications. Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

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20 pages, 3932 KiB

Open AccessArticle

Particle-Size-Dependent Delivery of Antitumoral miRNA Using Targeted Mesoporous Silica Nanoparticles

by Lisa Haddick, Wei Zhang, Sören Reinhard, Karin Möller, Hanna Engelke, Ernst Wagner and Thomas Bein

Pharmaceutics 2020, 12(6), 505; https://doi.org/10.3390/pharmaceutics12060505 - 02 Jun 2020

Cited by 28 | Viewed by 3772

Abstract

Multifunctional core-shell mesoporous silica nanoparticles (MSN) were tailored in size ranging from 60 to 160 nm as delivery agents for antitumoral microRNA (miRNA). The positively charged particle core with a pore diameter of about 5 nm and a stellate pore morphology allowed for [...] Read more.

Multifunctional core-shell mesoporous silica nanoparticles (MSN) were tailored in size ranging from 60 to 160 nm as delivery agents for antitumoral microRNA (miRNA). The positively charged particle core with a pore diameter of about 5 nm and a stellate pore morphology allowed for an internal, protective adsorption of the fragile miRNA cargo. A negatively charged particle surface enabled the association of a deliberately designed block copolymer with the MSN shell by charge-matching, simultaneously acting as a capping as well as endosomal release agent. Furthermore, the copolymer was functionalized with the peptide ligand GE11 targeting the epidermal growth factor receptor, EGFR. These multifunctional nanoparticles showed an enhanced uptake into EGFR-overexpressing T24 bladder cancer cells through receptor-mediated cellular internalization. A luciferase gene knock-down of up to 65% and additional antitumoral effects such as a decreased cell migration as well as changes in cell cycle were observed. We demonstrate that nanoparticles with a diameter of 160 nm show the fastest cellular internalization after a very short incubation time of 45 min and produce the highest level of gene knock-down. Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

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23 pages, 7511 KiB

Open AccessArticle

Cell Theranostics on Mesoporous Silicon Substrates

by Maria Laura Coluccio, Valentina Onesto, Giovanni Marinaro, Mauro Dell’Apa, Stefania De Vitis, Alessandra Imbrogno, Luca Tirinato, Gerardo Perozziello, Enzo Di Fabrizio, Patrizio Candeloro, Natalia Malara and Francesco Gentile

Pharmaceutics 2020, 12(5), 481; https://doi.org/10.3390/pharmaceutics12050481 - 25 May 2020

Cited by 6 | Viewed by 3183

Abstract

The adhesion, proliferation, and migration of cells over nanomaterials is regulated by a cascade of biochemical signals that originate at the interface of a cell with a substrate and propagate through the cytoplasm to the nucleus. The topography of the substrate plays a [...] Read more.

The adhesion, proliferation, and migration of cells over nanomaterials is regulated by a cascade of biochemical signals that originate at the interface of a cell with a substrate and propagate through the cytoplasm to the nucleus. The topography of the substrate plays a major role in this process. Cell adhesion molecules (CAMs) have a characteristic size of some nanometers and a range of action of some tens of nanometers. Controlling details of a surface at the nanoscale—the same dimensional over which CAMs operate—offers ways to govern the behavior of cells and create organoids or tissues with heretofore unattainable precision. Here, using electrochemical procedures, we generated mesoporous silicon surfaces with different values of pore size (PS ≈ 11 nm and PS ≈ 21 nm), roughness (Ra ≈ 7 nm and Ra ≈ 13 nm), and fractal dimension (Df ≈ 2.48 and Df ≈ 2.15). Using electroless deposition, we deposited over these substrates thin layers of gold nanoparticles. Resulting devices feature (i) nanoscale details for the stimulation and control of cell assembly, (ii) arrays of pores for drug loading/release, (iii) layers of nanostructured gold for the enhancement of the electromagnetic signal in Raman spectroscopy (SERS). We then used these devices as cell culturing substrates. Upon loading with the anti-tumor drug PtCl (O,O′-acac)(DMSO) we examined the rate of adhesion and growth of breast cancer MCF-7 cells under the coincidental effects of surface geometry and drug release. Using confocal imaging and SERS spectroscopy we determined the relative importance of nano-topography and delivery of therapeutics on cell growth—and how an unbalance between these competing agents can accelerate the development of tumor cells. Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

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20 pages, 3706 KiB

Open AccessArticle

Injectable Thermosensitive Formulation Based on Polyurethane Hydrogel/Mesoporous Glasses for Sustained Co-Delivery of Functional Ions and Drugs

by Monica Boffito, Carlotta Pontremoli, Sonia Fiorilli, Rossella Laurano, Gianluca Ciardelli and Chiara Vitale-Brovarone

Pharmaceutics 2019, 11(10), 501; https://doi.org/10.3390/pharmaceutics11100501 - 01 Oct 2019

Cited by 32 | Viewed by 3581

Abstract

Mini-invasively injectable hydrogels are widely attracting interest as smart tools for the co-delivery of therapeutic agents targeting different aspects of tissue/organ healing (e.g., neo-angiogenesis, inflammation). In this work, copper-substituted bioactive mesoporous glasses (Cu-MBGs) were prepared as nano- and micro-particles and successfully loaded with [...] Read more.

Mini-invasively injectable hydrogels are widely attracting interest as smart tools for the co-delivery of therapeutic agents targeting different aspects of tissue/organ healing (e.g., neo-angiogenesis, inflammation). In this work, copper-substituted bioactive mesoporous glasses (Cu-MBGs) were prepared as nano- and micro-particles and successfully loaded with ibuprofen through an incipient wetness method (loaded ibuprofen approx. 10% w/w). Injectable hybrid formulations were then developed by dispersing ibuprofen-loaded Cu-MBGs within thermosensitive hydrogels based on a custom-made amphiphilic polyurethane. This procedure showed almost no effects on the gelation potential (gelation at 37 °C within 3–5 min). Cu²⁺ and ibuprofen were co-released over time in a sustained manner with a significantly lower burst release compared to MBG particles alone (burst release reduction approx. 85% and 65% for ibuprofen and Cu²⁺, respectively). Additionally, released Cu²⁺ species triggered polyurethane chemical degradation, thus enabling a possible tuning of gel residence time at the pathological site. The overall results suggest that hybrid injectable thermosensitive gels could be successfully designed for the simultaneous localized co-delivery of multiple therapeutics. Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

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Review

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18 pages, 1196 KiB

Open AccessReview

Drug Delivery Applications of Three-Dimensional Printed (3DP) Mesoporous Scaffolds

by Tania Limongi, Francesca Susa, Marco Allione and Enzo di Fabrizio

Pharmaceutics 2020, 12(9), 851; https://doi.org/10.3390/pharmaceutics12090851 - 08 Sep 2020

Cited by 29 | Viewed by 5358

Abstract

Mesoporous materials are structures characterized by a well-ordered large pore system with uniform porous dimensions ranging between 2 and 50 nm. Typical samples are zeolite, carbon molecular sieves, porous metal oxides, organic and inorganic porous hybrid and pillared materials, silica clathrate and clathrate [...] Read more.

Mesoporous materials are structures characterized by a well-ordered large pore system with uniform porous dimensions ranging between 2 and 50 nm. Typical samples are zeolite, carbon molecular sieves, porous metal oxides, organic and inorganic porous hybrid and pillared materials, silica clathrate and clathrate hydrates compounds. Improvement in biochemistry and materials science led to the design and implementation of different types of porous materials ranging from rigid to soft two-dimensional (2D) and three-dimensional (3D) skeletons. The present review focuses on the use of three-dimensional printed (3DP) mesoporous scaffolds suitable for a wide range of drug delivery applications, due to their intrinsic high surface area and high pore volume. In the first part, the importance of the porosity of materials employed for drug delivery application was discussed focusing on mesoporous materials. At the end of the introduction, hard and soft templating synthesis for the realization of ordered 2D/3D mesostructured porous materials were described. In the second part, 3DP fabrication techniques, including fused deposition modelling, material jetting as inkjet printing, electron beam melting, selective laser sintering, stereolithography and digital light processing, electrospinning, and two-photon polymerization were described. In the last section, through recent bibliographic research, a wide number of 3D printed mesoporous materials, for in vitro and in vivo drug delivery applications, most of which relate to bone cells and tissues, were presented and summarized in a table in which all the technical and bibliographical details were reported. This review highlights, to a very cross-sectional audience, how the interdisciplinarity of certain branches of knowledge, as those of materials science and nano-microfabrication are, represent a growing valuable aid in the advanced forum for the science and technology of pharmaceutics and biopharmaceutics. Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

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33 pages, 1416 KiB

Open AccessReview

Multimodal Decorations of Mesoporous Silica Nanoparticles for Improved Cancer Therapy

by Sugata Barui and Valentina Cauda

Pharmaceutics 2020, 12(6), 527; https://doi.org/10.3390/pharmaceutics12060527 - 08 Jun 2020

Cited by 41 | Viewed by 7431

Abstract

The presence of leaky vasculature and the lack of lymphatic drainage of small structures by the solid tumors formulate nanoparticles as promising delivery vehicles in cancer therapy. In particular, among various nanoparticles, the mesoporous silica nanoparticles (MSN) exhibit numerous outstanding features, including mechanical [...] Read more.

The presence of leaky vasculature and the lack of lymphatic drainage of small structures by the solid tumors formulate nanoparticles as promising delivery vehicles in cancer therapy. In particular, among various nanoparticles, the mesoporous silica nanoparticles (MSN) exhibit numerous outstanding features, including mechanical thermal and chemical stability, huge surface area and ordered porous interior to store different anti-cancer therapeutics with high loading capacity and tunable release mechanisms. Furthermore, one can easily decorate the surface of MSN by attaching ligands for active targeting specifically to the cancer region exploiting overexpressed receptors. The controlled release of drugs to the disease site without any leakage to healthy tissues can be achieved by employing environment responsive gatekeepers for the end-capping of MSN. To achieve precise cancer chemotherapy, the most desired delivery system should possess high loading efficiency, site-specificity and capacity of controlled release. In this review we will focus on multimodal decorations of MSN, which is the most demanding ongoing approach related to MSN application in cancer therapy. Herein, we will report about the recently tried efforts for multimodal modifications of MSN, exploiting both the active targeting and stimuli responsive behavior simultaneously, along with individual targeted delivery and stimuli responsive cancer therapy using MSN. Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

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42 pages, 7937 KiB

Open AccessReview

Mesoporous Silica Nanoparticles as Carriers for Therapeutic Biomolecules

by Rafael R. Castillo, Daniel Lozano and María Vallet-Regí

Pharmaceutics 2020, 12(5), 432; https://doi.org/10.3390/pharmaceutics12050432 - 07 May 2020

Cited by 68 | Viewed by 5465

Abstract

The enormous versatility of mesoporous silica nanoparticles permits the creation of a large number of nanotherapeutic systems for the treatment of cancer and many other pathologies. In addition to the controlled release of small drugs, these materials allow a broad number of molecules [...] Read more.

The enormous versatility of mesoporous silica nanoparticles permits the creation of a large number of nanotherapeutic systems for the treatment of cancer and many other pathologies. In addition to the controlled release of small drugs, these materials allow a broad number of molecules of a very different nature and sizes. In this review, we focus on biogenic species with therapeutic abilities (proteins, peptides, nucleic acids, and glycans), as well as how nanotechnology, in particular silica-based materials, can help in establishing new and more efficient routes for their administration. Indeed, since the applicability of those combinations of mesoporous silica with bio(macro)molecules goes beyond cancer treatment, we address a classification based on the type of therapeutic action. Likewise, as illustrative content, we highlight the most typical issues and problems found in the preparation of those hybrid nanotherapeutic materials. Full article

(This article belongs to the Special Issue Mesoporous Materials for Drug Delivery and Theranostics)

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