Research

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14 pages, 26004 KiB

Open AccessArticle

Loading of Porous Functionalized Calcium Carbonate Microparticles: Distribution Analysis with Focused Ion Beam Electron Microscopy and Mercury Porosimetry

by Maryam Farzan, Roger Roth, Gabriela Québatte, Joachim Schoelkopf, Jörg Huwyler and Maxim Puchkov

Pharmaceutics 2019, 11(1), 32; https://doi.org/10.3390/pharmaceutics11010032 - 15 Jan 2019

Cited by 14 | Viewed by 3920

Abstract

Accurate analysis of intraparticle distribution of substances within porous drug carriers is important to optimize loading and subsequent processing. Mercury intrusion porosimetry, a common technique used for characterization of porous materials, assumes cylindrical pore geometry, which may lead to misinterpretation. Therefore, imaging techniques [...] Read more.

Accurate analysis of intraparticle distribution of substances within porous drug carriers is important to optimize loading and subsequent processing. Mercury intrusion porosimetry, a common technique used for characterization of porous materials, assumes cylindrical pore geometry, which may lead to misinterpretation. Therefore, imaging techniques such as focused ion beam scanning electron microscopy (FIB-SEM) help to better interpret these results. The purpose of this study was to investigate the differences between mercury intrusion and scanning electron microscopy and to identify the limitations of each method. Porous microparticles, functionalized calcium carbonate, were loaded with bovine serum albumin and dipalmitoylphosphatidylcholine (DPPC) by solvent evaporation and results of the pore size distribution obtained by both methods were compared. The internal structure of the novel pharmaceutical excipient, functionalized calcium carbonate, was revealed for the first time. Our results demonstrated that image analysis provides a closer representation of the material distribution since it was possible to discriminate between blocked and filled pores. The physical nature of the loaded substances is critical for the deposition within the pores of functionalized calcium carbonate. We conclude, that a combination of mercury intrusion porosimetry and focused ion beam scanning electron microscopy allows for a reliable analysis of sub-micron porous structures of particulate drug carriers. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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18 pages, 2928 KiB

Open AccessArticle

Preparation and Study of the Antibacterial Applications and Oxidative Stress Induction of Copper Maleamate-Functionalized Mesoporous Silica Nanoparticles

by Diana Díaz-García, Perla R. Ardiles, Sanjiv Prashar, Antonio Rodríguez-Diéguez, Paulina L. Páez and Santiago Gómez-Ruiz

Pharmaceutics 2019, 11(1), 30; https://doi.org/10.3390/pharmaceutics11010030 - 14 Jan 2019

Cited by 43 | Viewed by 4073

Abstract

Mesoporous silica nanoparticles (MSNs) are an interesting class of nanomaterials with potential applications in different therapeutic areas and that have been extensively used as drug carriers in different fields of medicine. The present work is focused on the synthesis of MSNs containing a [...] Read more.

Mesoporous silica nanoparticles (MSNs) are an interesting class of nanomaterials with potential applications in different therapeutic areas and that have been extensively used as drug carriers in different fields of medicine. The present work is focused on the synthesis of MSNs containing a maleamato ligand (MSN-maleamic) and the subsequent coordination of copper(II) ions (MSN-maleamic-Cu) for the exploration of their potential application as antibacterial agents. The Cu-containing nanomaterials have been characterized by different techniques and the preliminary antibacterial effect of the supported maleamato-copper(II) complexes has been tested against two types of bacteria (Gram positive and Gram negative) in different assays to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The biological results showed a moderate antibacterial activity against Escherichia coli which motivated a more detailed study of the antibacterial mechanism of action of the synthesized maleamate-containing nanosystems and whose findings showed oxidative stress generation in bacterial cells. All the prepared nanomaterials were also tested as catalysts in the “solvent free” selective oxidation of benzyl alcohol, to observe if there is a potential correlation between the catalytic oxidation capacity of the materials and the observed oxidative stress in bacteria. This may help in the future, for a more accurate rational design of antibacterial nanosystems, based on their observed catalytic oxidation activity. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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16 pages, 3586 KiB

Open AccessArticle

Enhanced Solubility, Permeability and Anticancer Activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles

by Anand Kumar Meka, Laura J. Jenkins, Mercedes Dàvalos-Salas, Naisarg Pujara, Kuan Yau Wong, Tushar Kumeria, John M. Mariadason and Amirali Popat

Pharmaceutics 2018, 10(4), 283; https://doi.org/10.3390/pharmaceutics10040283 - 17 Dec 2018

Cited by 47 | Viewed by 6042

Abstract

Suberoylanilide hydroxamic acid (SAHA) or vorinostat (VOR) is a potent inhibitor of class I histone deacetylases (HDACs) that is approved for the treatment of cutaneous T-cell lymphoma. However, it has the intrinsic limitations of low water solubility and low permeability which reduces its [...] Read more.

Suberoylanilide hydroxamic acid (SAHA) or vorinostat (VOR) is a potent inhibitor of class I histone deacetylases (HDACs) that is approved for the treatment of cutaneous T-cell lymphoma. However, it has the intrinsic limitations of low water solubility and low permeability which reduces its clinical potential especially when given orally. Packaging of drugs within ordered mesoporous silica nanoparticles (MSNs) is an emerging strategy for increasing drug solubility and permeability of BCS (Biopharmaceutical Classification System) class II and IV drugs. In this study, we encapsulated vorinostat within MSNs modified with different functional groups, and assessed its solubility, permeability and anti-cancer efficacy in vitro. Compared to free drug, the solubility of vorinostat was enhanced 2.6-fold upon encapsulation in pristine MSNs (MCM-41-VOR). Solubility was further enhanced when MSNs were modified with silanes having amino (3.9 fold) or phosphonate (4.3 fold) terminal functional groups. Moreover, permeability of vorinostat into Caco-2 human colon cancer cells was significantly enhanced for MSN-based formulations, particularly MSNs modified with amino functional group (MCM-41-NH₂-VOR) where it was enhanced ~4 fold. Compared to free drug, vorinostat encapsulated within amino-modified MSNs robustly induced histone hyperacetylation and expression of established histone deacetylase inhibitor (HDACi)-target genes, and induced extensive apoptosis in HCT116 colon cancer cells. Similar effects were observed on apoptosis induction in HH cutaneous T-cell lymphoma cells. Thus, encapsulation of the BCS class IV molecule vorinostat within MSNs represents an effective strategy for improving its solubility, permeability and anti-tumour activity. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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18 pages, 4461 KiB

Open AccessArticle

Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures

by Diti Desai, Malin Åkerfelt, Neeraj Prabhakar, Mervi Toriseva, Tuomas Näreoja, Jixi Zhang, Matthias Nees and Jessica M. Rosenholm

Pharmaceutics 2018, 10(4), 237; https://doi.org/10.3390/pharmaceutics10040237 - 17 Nov 2018

Cited by 9 | Viewed by 4619

Abstract

Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were [...] Read more.

Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used: MSNs with a surface-grown poly(ethylene imine), PEI, coating only for hydrophobic cargo and MSNs with lipid bilayers covalently coupled to the PEI layer as a diffusion barrier for hydrophilic cargo. First, the effect of hydrophobicity corresponding to loading degree (hydrophobic cargo) as well as surface charge (hydrophilic cargo) on intracellular drug release was studied on the cellular level. All incorporated agents were able to release to varying degrees from the endosomes into the cytoplasm in a loading degree (hydrophobic) or surface charge (hydrophilic) dependent manner as detected by live cell imaging. When administered to organotypic 3D tumor models, the hydrophilic versus hydrophobic cargo-carrying MSNs showed remarkable differences in labeling efficiency, which in this case also corresponds to drug delivery efficacy in 3D. The obtained results could thus indicate design aspects to be taken into account for the development of efficacious intracellular drug delivery systems, especially in the translation from standard 2D culture to more biologically relevant organotypic 3D cultures. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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14 pages, 5008 KiB

Open AccessArticle

Fabrication and Characterization of Strontium-Substituted Hydroxyapatite-CaO-CaCO₃ Nanofibers with a Mesoporous Structure as Drug Delivery Carriers

by Shiao-Wen Tsai, Wen-Xin Yu, Pai-An Hwang, Sheng-Siang Huang, Hsiu-Mei Lin, Yu-Wei Hsu and Fu-Yin Hsu

Pharmaceutics 2018, 10(4), 179; https://doi.org/10.3390/pharmaceutics10040179 - 08 Oct 2018

Cited by 35 | Viewed by 4740

Abstract

Hydroxyapatite (HAp) is the main inorganic component and an essential part of hard bone and teeth. Due to its excellent biocompatibility, bioactivity, and osteoconductivity, synthetic HAp has been widely used as a bone substitute, cell carrier, and therapeutic gene or drug carrier. Recently, [...] Read more.

Hydroxyapatite (HAp) is the main inorganic component and an essential part of hard bone and teeth. Due to its excellent biocompatibility, bioactivity, and osteoconductivity, synthetic HAp has been widely used as a bone substitute, cell carrier, and therapeutic gene or drug carrier. Recently, numerous studies have demonstrated that strontium-substituted hydroxyapatite (SrHAp) not only enhances osteogenesis but also inhibits adipogenesis in mesenchymal stem cells. Mesoporous SrHAp has been successfully synthesized via a traditional template-based process and has been found to possess better drug loading and release efficiencies than SrHAp. In this study, strontium-substituted hydroxyapatite-CaO-CaCO₃ nanofibers with a mesoporous structure (mSrHANFs) were fabricated using a sol–gel method followed by electrospinning. X-ray diffraction analysis revealed that the contents of CaO and CaCO₃ in the mSrHANFs decreased as the doping amount of Sr increased. Scanning electron microscopy (SEM) images showed that the average diameter of the mSrHANFs was approximately 200~300 nm. The N₂ adsorption–desorption isotherms demonstrated that the mSrHANFs possessed a mesoporous structure and that the average pore size was approximately 20~25 nm. Moreover, the mSrHANFs had excellent drug- loading efficiency and could retard the burst release of tetracycline (TC) to maintain antibacterial activity for over 3 weeks. Hence, mSrHANFs have the potential to be used as drug carriers in bone tissue engineering. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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Review

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29 pages, 6394 KiB

Open AccessFeature PaperReview

Mesoporous Silica Materials as Drug Delivery: “The Nightmare” of Bacterial Infection

by Marina Martínez-Carmona, Yurii K. Gun’ko and María Vallet-Regí

Pharmaceutics 2018, 10(4), 279; https://doi.org/10.3390/pharmaceutics10040279 - 15 Dec 2018

Cited by 73 | Viewed by 8305

Abstract

Mesoporous silica materials (MSM) have a great surface area and a high pore volume, meaning that they consequently have a large loading capacity, and have been demonstrated to be unique candidates for the treatment of different pathologies, including bacterial infection. In this text, [...] Read more.

Mesoporous silica materials (MSM) have a great surface area and a high pore volume, meaning that they consequently have a large loading capacity, and have been demonstrated to be unique candidates for the treatment of different pathologies, including bacterial infection. In this text, we review the multiple ways of action in which MSM can be used to fight bacterial infection, including early detection, drug release, targeting bacteria or biofilm, antifouling surfaces, and adjuvant capacity. This review focus mainly on those that act as a drug delivery system, and therefore that have an essential characteristic, which is their great loading capacity. Since MSM have advantages in all stages of combatting bacterial infection; its prevention, detection and finally in its treatment, we can venture to talk about them as the “nightmare of bacteria”. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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20 pages, 1822 KiB

Open AccessReview

Drug-Loaded Biomimetic Ceramics for Tissue Engineering

by Patricia Diaz-Rodriguez, Mirian Sánchez and Mariana Landin

Pharmaceutics 2018, 10(4), 272; https://doi.org/10.3390/pharmaceutics10040272 - 13 Dec 2018

Cited by 44 | Viewed by 4403

Abstract

The mimesis of biological systems has been demonstrated to be an adequate approach to obtain tissue engineering scaffolds able to promote cell attachment, proliferation, and differentiation abilities similar to those of autologous tissues. Bioceramics are commonly used for this purpose due to their [...] Read more.

The mimesis of biological systems has been demonstrated to be an adequate approach to obtain tissue engineering scaffolds able to promote cell attachment, proliferation, and differentiation abilities similar to those of autologous tissues. Bioceramics are commonly used for this purpose due to their similarities to the mineral component of hard tissues as bone. Furthermore, biomimetic scaffolds are frequently loaded with diverse therapeutic molecules to enhance their biological performance, leading to final products with advanced functionalities. In this review, we aim to describe the already developed bioceramic-based biomimetic systems for drug loading and local controlled release. We will discuss the mechanisms used for the inclusion of therapeutic molecules on the designed systems, paying special attention to the identification of critical parameters that modulate drug loading and release kinetics on these scaffolds. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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18 pages, 1128 KiB

Open AccessReview

Dealing with Skin and Blood-Brain Barriers: The Unconventional Challenges of Mesoporous Silica Nanoparticles

by Alessandra Nigro, Michele Pellegrino, Marianna Greco, Alessandra Comandè, Diego Sisci, Luigi Pasqua, Antonella Leggio and Catia Morelli

Pharmaceutics 2018, 10(4), 250; https://doi.org/10.3390/pharmaceutics10040250 - 01 Dec 2018

Cited by 36 | Viewed by 4946

Abstract

Advances in nanotechnology for drug delivery are fostering significant progress in medicine and diagnostics. The multidisciplinary nature of the nanotechnology field encouraged the development of innovative strategies and materials to treat a wide range of diseases in a highly specific way, which allows [...] Read more.

Advances in nanotechnology for drug delivery are fostering significant progress in medicine and diagnostics. The multidisciplinary nature of the nanotechnology field encouraged the development of innovative strategies and materials to treat a wide range of diseases in a highly specific way, which allows reducing the drug dosage and, consequently, improving the patient’s compliance. Due to their good biocompatibility, easy synthesis, and high versatility, inorganic frameworks represent a valid tool to achieve this aim. In this context, Mesoporous Silica Nanoparticles (MSNs) are emerging in the biomedical field. For their ordered porosity and high functionalizable surface, achievable with an inexpensive synthesis process and being non-hazardous to biological tissues, MSNs offer ideal solutions to host, protect, and transport drugs to specific target sites. Extensive literature exists on the use of MSNs as targeted vehicles for systemic (chemo) therapy and for imaging/diagnostic purposes. However, the aim of this review is to give an overview of the last updates on the potential applications of the MSNs for Topical Drug Delivery (TDD) and as drug delivery systems into the brain, discussing their performances and advantages in dealing with these intriguing biological barriers. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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15 pages, 2975 KiB

Open AccessReview

Diatoms Green Nanotechnology for Biosilica-Based Drug Delivery Systems

by Monica Terracciano, Luca De Stefano and Ilaria Rea

Pharmaceutics 2018, 10(4), 242; https://doi.org/10.3390/pharmaceutics10040242 - 20 Nov 2018

Cited by 71 | Viewed by 8840

Abstract

Diatom microalgae are the most outstanding natural source of porous silica. The diatom cell is enclosed in a three-dimensional (3-D) ordered nanopatterned silica cell wall, called frustule. The unique properties of the diatom frustule, including high specific surface area, thermal stability, biocompatibility, and [...] Read more.

Diatom microalgae are the most outstanding natural source of porous silica. The diatom cell is enclosed in a three-dimensional (3-D) ordered nanopatterned silica cell wall, called frustule. The unique properties of the diatom frustule, including high specific surface area, thermal stability, biocompatibility, and tailorable surface chemistry, make diatoms really promising for biomedical applications. Moreover, they are easy to cultivate in an artificial environment and there is a large availability of diatom frustules as fossil material (diatomite) in several areas of the world. For all these reasons, diatoms are an intriguing alternative to synthetic materials for the development of low-cost drug delivery systems. This review article focuses on the possible use of diatom-derived silica as drug carrier systems. The functionalization strategies of diatom micro/nanoparticles for improving their biophysical properties, such as cellular internalization and drug loading/release kinetics, are described. In addition, the realization of hybrid diatom-based devices with advanced properties for theranostics and targeted or augmented drug delivery applications is also discussed. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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35 pages, 4340 KiB

Open AccessReview

Porous Inorganic Carriers Based on Silica, Calcium Carbonate and Calcium Phosphate for Controlled/Modulated Drug Delivery: Fresh Outlook and Future Perspectives

by Alexey D. Trofimov, Anna A. Ivanova, Mikhail V. Zyuzin and Alexander S. Timin

Pharmaceutics 2018, 10(4), 167; https://doi.org/10.3390/pharmaceutics10040167 - 25 Sep 2018

Cited by 97 | Viewed by 9250

Abstract

Porous inorganic nanostructured materials are widely used nowadays as drug delivery carriers due to their adventurous features: suitable architecture, large surface area and stability in the biological fluids. Among the different types of inorganic porous materials, silica, calcium carbonate, and calcium phosphate have [...] Read more.

Porous inorganic nanostructured materials are widely used nowadays as drug delivery carriers due to their adventurous features: suitable architecture, large surface area and stability in the biological fluids. Among the different types of inorganic porous materials, silica, calcium carbonate, and calcium phosphate have received significant attention in the last decade. The use of porous inorganic materials as drug carriers for cancer therapy, gene delivery etc. has the potential to improve the life expectancy of the patients affected by the disease. The main goal of this review is to provide general information on the current state of the art of synthesis of the inorganic porous particles based on silica, calcium carbonate and calcium phosphate. Special focus is dedicated to the loading capacity, controllable release of drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external noninvasive stimuli (e.g., light, magnetic field, and ultrasound). Moreover, the diverse compounds to deliver with silica, calcium carbonate and calcium phosphate particles, ranging from the commercial drugs to genetic materials are also discussed. Full article

(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)

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