Size, Stability, and Porosity of Mesoporous Nanoparticles Characterized with Light Scattering

Silicon-based mesoporous nanoparticles have been extensively studied to meet the challenges in the drug delivery. Functionality of these nanoparticles depends on their properties which are often changing as a function of particle size and surrounding medium. Widely used characterization methods, dynamic light scattering (DLS), and transmission electron microscope (TEM) have both their weaknesses. We hypothesize that conventional light scattering (LS) methods can be used for a rigorous characterization of medium sensitive nanoparticles’ properties, like size, stability, and porosity. Two fundamentally different silicon-based nanoparticles were made: porous silicon (PSi) from crystalline silicon and silica nanoparticles (SN) through sol-gel process. We studied the properties of these mesoporous nanoparticles with two different multiangle LS techniques, DLS and static light scattering (SLS), and compared the results to dry-state techniques, TEM, and nitrogen sorption. Comparison of particle radius from TEM and DLS revealed significant overestimation of the DLS result. Regarding to silica nanoparticles, the overestimation was attributed to agglomeration by analyzing radius of gyration and hydrodynamic radius. In case of PSi nanoparticles, strong correlation between LS result and specific surface area was found. Our results suggest that the multiangle LS methods could be used for the size, stability, and structure characterization of mesoporous nanoparticles.Peer reviewe

Quantification and qualitative effects of different PEGylations on Poly(butyl cyanoacrylate) nanoparticles

Protein adsorption on nanoparticles (NPs) used in nanomedicine leads to opsonization and activation of the complement system in blood, which substantially reduces the blood circulation time of NPs. The most commonly used method to avoid protein adsorption, is to coat the NPs with polyethylene glycol, so called PEGylation. Although PEGylation is of utmost importance for designing the in vivo behavior of the NP, there is still a considerable lack of methods for characterization and fundamental understanding related to the PEGylation of NPs. In this work we have studied four different poly(butyl cyanoacrylate) (PBCA) NPs , PEGylated with different types of PEG-based non-ionic surfactants–Jeffamine M-2070, Brij L23, Kolliphor HS 15, Pluronic F68–or combinations thereof. We evaluated the PEGylation, both quantitatively by nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), and qualitatively by studying zeta-potential, protein adsorption, diffusion, cellular interactions and blood circulation half-life. We found that NMR and ToF-SIMS are complementary methods, while TGA is less suitable to quantitate PEG on polymeric NPs. It was found that longer PEG increases both blood circulation time and diffusion of NPs in collagen gels

Design and evaluation of nanoparticle-based delivery systems : towards cancer theranostics

The design, characterization and applicability of nanoparticle (NP)-based delivery systems intended for cancer theranostics, are presented in this thesis. Mesoporous silica nanoparticles (MSNs) have been widely established as biocompatible and efficient carriers of hydrophobic molecules, such as drugs for in vitro and in vivo tumor targeting. Although their intracellular delivery and cargo release have been demonstrated, knowledge of the underlying drug release mechanisms still remain unclear. For future control and prediction of these parameters, which from a clinical perspective are imperative to all drug delivery systems (DDSs), the release of hydrophobic cargo from MSNs is studied. In simple aqueous solvents, cargo release is strongly associated with nanocarrier degradation, whereas in media mimicking intracellular conditions, where lipids or hydrophobic structures are present, the physicochemical properties of the cargo molecule itself and its interactions with the surrounding medium are the release-governing parameters. For comparison, the relationship between intracellular cargo release and degradation of poly(alkylcyanoacrylate) (PACA) nanocarriers is also investigated, for which the release is found to be dependent on the biodegradation of the carrier. The influence of NP monomer composition on intracellular delivery and the role of different endocytosis pathways are also assessed. This thesis moreover presents a novel multifunctional composite NP for combined optical imaging, tracking and drug delivery. The used approaches include creation and optimization of core-shell nanostructures of photoluminescent (PL) nanodiamonds (NDs) encapsulated within mesoporous silica shells that allow tuning of the composite NP size and loading of hydrophobic cargo molecules. Through subsequent surface engineering, efficient passive uptake by endocytosis, followed by intracellular release of cargo, is achieved and displayed by optical fluorescence imaging. The approaches presented in this thesis are highly interdisciplinary, placed at the meeting point between chemistry, physics, engineering, biotechnology and pharmaceutical sciences, and provide a basis for the rational design and evaluation of NP-based DDSs, intended for cancer theranostics, mainly by intravenous (IV) administration

Feasibility Study of Mesoporous Silica Particles for Pulmonary Drug Delivery : Therapeutic Treatment with Dexamethasone in a Mouse Model of Airway Inflammation

Diseases in the respiratory tract rank among the leading causes of death in the world, and thus novel and optimized treatments are needed. The lungs offer a large surface for drug absorption, and the inhalation of aerosolized drugs are a well-established therapeutic modality for local treatment of lung conditions. Nanoparticle-based drug delivery platforms are gaining importance for use through the pulmonary route. By using porous carrier matrices, higher doses of especially poorly soluble drugs can be administered locally, reducing their side effects and improving their biodistribution. In this study, the feasibility of mesoporous silica particles (MSPs) as carriers for anti-inflammatory drugs in the treatment of airway inflammation was investigated. Two different sizes of particles on the micron and nanoscale (1 mu m and 200 nm) were produced, and were loaded with dexamethasone (DEX) to a loading degree of 1:1 DEX:MSP. These particles were further surface-functionalized with a polyethylene glycol-polyethylene imine (PEG-PEI) copolymer for optimal aqueous dispersibility. The drug-loaded particles were administered as an aerosol, through inhalation to two different mice models of neutrophil-induced (by melphalan or lipopolysaccharide) airway inflammation. The mice received treatment with either DEX-loaded MSPs or, as controls, empty MSPs or DEX only; and were evaluated for treatment effects 24 h after exposure. The results show that the MEL-induced airway inflammation could be treated by the DEX-loaded MSPs to the same extent as free DEX. Interestingly, in the case of LPS-induced inflammation, even the empty MSPs significantly down-modulated the inflammatory response. This study highlights the potential of MSPs as drug carriers for the treatment of diseases in the airways

Size, Stability, and Porosity of Mesoporous Nanoparticles Characterized with Light Scattering

Silicon-based mesoporous nanoparticles have been extensively studied to meet the challenges in the drug delivery. Functionality of these nanoparticles depends on their properties which are often changing as a function of particle size and surrounding medium. Widely used characterization methods, dynamic light scattering (DLS), and transmission electron microscope (TEM) have both their weaknesses. We hypothesize that conventional light scattering (LS) methods can be used for a rigorous characterization of medium sensitive nanoparticles' properties, like size, stability, and porosity. Two fundamentally different silicon-based nanoparticles were made: porous silicon (PSi) from crystalline silicon and silica nanoparticles (SN) through sol-gel process. We studied the properties of these mesoporous nanoparticles with two different multiangle LS techniques, DLS and static light scattering (SLS), and compared the results to dry-state techniques, TEM, and nitrogen sorption. Comparison of particle radius from TEM and DLS revealed significant overestimation of the DLS result. Regarding to silica nanoparticles, the overestimation was attributed to agglomeration by analyzing radius of gyration and hydrodynamic radius. In case of PSi nanoparticles, strong correlation between LS result and specific surface area was found. Our results suggest that the multiangle LS methods could be used for the size, stability, and structure characterization of mesoporous nanoparticles

Additional file 1: of Size, Stability, and Porosity of Mesoporous Nanoparticles Characterized with Light Scattering

Contains following supplementary materials: fabrication of porous silicon nanoparticles, fabrication of silica nanoparticles, summary of silica nanoparticles' preparation conditions, summary of log-normal fitting results, absorbance of used nanoparticles, nitrogen sorption isotherms, additional TEM graphs from silica nanoparticles, fractal dimension analysis for SLS results and Kratky plots, all the studied correlations and measured zeta potential distributions. (DOCX 11779 kb

Quantification and Qualitative Effects of Different PEGylations on Poly(butyl cyanoacrylate) Nanoparticles

Protein adsorption on nanoparticles (NPs) used in nanomedicine leads to opsonization and activation of the complement system in blood, which substantially reduces the blood circulation time of NPs. The most commonly used method to avoid protein adsorption is to coat the NPs with polyethylene glycol, so-called PEGylation. Although PEGylation is of utmost importance for designing the in vivo behavior of the NP, there is still a considerable lack of methods for characterization and fundamental understanding related to the PEGylation of NPs. In this work we have studied four different poly(butyl cyanoacrylate) (PBCA) NPs, PEGylated with different types of PEG-based nonionic surfactants—Jeffamine M-2070, Brij L23, Kolliphor HS 15, Pluronic F68—or combinations thereof. We evaluated the PEGylation, both quantitatively by nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and time-of-flight secondary ion mass spectrometry (ToF-SIMS) and qualitatively by studying ζ-potential, protein adsorption, diffusion, cellular interactions, and blood circulation half-life. We found that NMR and ToF-SIMS are complementary methods, while TGA is less suitable to quantitate PEG on polymeric NPs. It was found that longer PEG increases both blood circulation time and diffusion of NPs in collagen gels