Controlled Release of Volatile Antimicrobial Compounds from Mesoporous Silica Nanocarriers for Active Food Packaging Applications.

Essential oils and their active components have been extensively reported in the literature for their efficient antimicrobial, antioxidant and antifungal properties. However, the sensitivity of these volatile compounds towards heat, oxygen and light limits their usage in real food packaging applications. The encapsulation of these compounds into inorganic nanocarriers, such as nanoclays, has been shown to prolong the release and protect the compounds from harsh processing conditions. Nevertheless, these systems have limited shelf stability, and the release is of limited control. Thus, this study presents a mesoporous silica nanocarrier with a high surface area and well-ordered protective pore structure for loading large amounts of natural active compounds (up to 500 mg/g). The presented loaded nanocarriers are shelf-stable with a very slow initial release which levels out at 50% retention of the encapsulated compounds after 2 months. By the addition of simulated drip-loss from chicken, the release of the compounds is activated and gives an antimicrobial effect, which is demonstrated on the foodborne spoilage bacteria Brochothrixthermosphacta and the potentially pathogenic bacteria Escherichia coli. When the release of the active compounds is activated, a ≥4-log reduction in the growth of B. thermosphacta and a 2-log reduction of E. coli is obtained, after only one hour of incubation. During the same one-hour incubation period the dry nanocarriers gave a negligible inhibitory effect. By using the proposed nanocarrier system, which is activated by the food product itself, increased availability of the natural antimicrobial compounds is expected, with a subsequent controlled antimicrobial effect.

Inorganic Nanocarriers for Encapsulation of Natural Antimicrobial Compounds for Potential Food Packaging Application: A Comparative Study.

Design and development of novel inorganic nanocarriers for encapsulation of natural antimicrobial substances for food packaging applications have received great interest during the last years. Natural nanoclays are the most investigated nanocarriers and recently interest has also grown in the synthetically produced porous silica particles. However, these different carrier matrices have not been compared in terms of their loading capability and subsequent release. In this study, the feasibility of porous silica particles (with different pore structures and/or surface functionalities) and commercially available nanoclays were evaluated as encapsulation matrices. Two well-studied antimicrobial substances, thymol and curcumin, were chosen as volatile and non-volatile model compounds, respectively. The encapsulation efficiency, and the subsequent dispersibility and release, of these substances differed significantly among the nanocarriers. Encapsulation of the volatile compound highly depends on the inner surface area, i.e., the protective pore environment, and an optimal nanocarrier can protect the encapsulated thymol from volatilization. For the non-volatile compound, only the release rate and dispersibility are affected by the pore structure. Further, water-activated release of the volatile compound was demonstrated and exhibited good antimicrobial efficacy in the vapor phase against Staphylococcus aureus. This comparative study can provide a base for selecting the right nanocarrier aimed at a specific food packaging application. No nanocarrier can be considered as a universally applicable one.

Nanocomposites for Food Packaging Applications: An Overview.

There is a strong drive in industry for packaging solutions that contribute to sustainable development by targeting a circular economy, which pivots around the recyclability of the packaging materials. The aim is to reduce traditional plastic consumption and achieve high recycling efficiency while maintaining the desired barrier and mechanical properties. In this domain, packaging materials in the form of polymer nanocomposites (PNCs) can offer the desired functionalities and can be a potential replacement for complex multilayered polymer structures. There has been an increasing interest in nanocomposites for food packaging applications, with a five-fold rise in the number of published articles during the period 2010-2019. The barrier, mechanical, and thermal properties of the polymers can be significantly improved by incorporating low concentrations of nanofillers. Furthermore, antimicrobial and antioxidant properties can be introduced, which are very relevant for food packaging applications. In this review, we will present an overview of the nanocomposite materials for food packaging applications. We will briefly discuss different nanofillers, methods to incorporate them in the polymer matrix, and surface treatments, with a special focus on the barrier, antimicrobial, and antioxidant properties. On the practical side migration issues, consumer acceptability, recyclability, and toxicity aspects will also be discussed.

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 µm 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.

Solution Conformation of Polymer Brushes Determines Their Interactions with DNA and Transfection Efficiency.

Polymer brush-functionalized nanomaterials offer interesting features for the design of gene delivery vectors as their physicochemical and structural properties can be designed independently of the chemistry, size and shape of the nanomaterial core. However, little is known of the parameters regulating the adsorption and infiltration of DNA molecules at the surface of positively charged polymer brushes, despite the importance of such processes for gene delivery. Here we investigate the role of the molecular environment (e.g., pH, type of buffer, concentration) on the interactions between plasmid DNA and positively charged poly(dimethylaminoethyl methacrylate) (PDMAEMA) brushes using a combination of light scattering, electrophoretic light scattering, in situ ellipsometry, and surface plasmon resonance. We show that the conformation of swollen PDMAEMA brushes is modulated by the surrounding buffer and that this impacts strongly on the ability of such brushes and nanomaterials based on these coatings to complex DNA molecules. In turn, the levels of transfection efficiency measured correlate with changes in brush conformation and DNA binding. Therefore, this work demonstrates the importance of molecular design of polymer brushes to control DNA complexation and release in order to optimize the performance of polymer brush-functionalized nanomaterials for gene delivery applications.

Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery.

Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with the challenge being to deliver it in a sustained manner. The combination of mesoporous silica nanoparticles (MSNs) and polycations in the confined pore space allows for incorporation and controlled release of therapeutic siRNA payloads. We hereby constructed MSNs with expanded mesopores and pore-surface-hyperbranched poly(ethyleneimine) (PEI) tethered with redox-cleavable linkers that could carry a high payload of siRNA (120 mg·g-1). The developed nanocarriers were efficiently taken up by cancer cells and were subsequently able to escape to the cytoplasm from the endosomes, most likely owing to the integrated PEI. Triggered by the intracellular redox conditions, the siRNA was sustainably released inside the cells over a period of several days. Functionality of siRNAs was demonstrated by using cell-killing siRNA as cargo. Despite not being the aim of the developed system, in vitro experiments using cell-killing siRNAs showed that the efficacy of siRNA transfection was comparable to the commercial in vitro transfection agent Lipofectamine. Consequently, the developed MSN-based delivery system offers a potential approach to hybrid nanocarriers for more efficient and long-term siRNA delivery and, in a longer perspective, in vivo gene silencing for RNA interference (RNAi) therapy.

Prolonged Dye Release from Mesoporous Silica-Based Imaging Probes Facilitates Long-Term Optical Tracking of Cell Populations In Vivo.

Nanomedicine is gaining ground worldwide in therapy and diagnostics. Novel nanoscopic imaging probes serve as imaging tools for studying dynamic biological processes in vitro and in vivo. To allow detectability in the physiological environment, the nanostructure-based probes need to be either inherently detectable by biomedical imaging techniques, or serve as carriers for existing imaging agents. In this study, the potential of mesoporous silica nanoparticles carrying commercially available fluorochromes as self-regenerating cell labels for long-term cellular tracking is investigated. The particle surface is organically modified for enhanced cellular uptake, the fluorescence intensity of labeled cells is followed over time both in vitro and in vivo. The particles are not exocytosed and particles which escaped cells due to cell injury or death are degraded and no labeling of nontargeted cell populations are observed. The labeling efficiency is significantly improved as compared to that of quantum dots of similar emission wavelength. Labeled human breast cancer cells are xenotransplanted in nude mice, and the fluorescent cells can be detected in vivo for a period of 1 month. Moreover, ex vivo analysis reveals fluorescently labeled metastatic colonies in lymph node and rib, highlighting the capability of the developed probes for tracking of metastasis.

Rational evaluation of the utilization of PEG-PEI copolymers for the facilitation of silica nanoparticulate systems in biomedical applications.

HYPOTHESIS: Polymer constructs are often applied in nanoparticulate systems to expand their applicability. One such common macromolecular modifier is poly(ethylene imine) - poly(ethylene glycol) copolymers. Despite their quite widespread use, and considering that interaction and stabilization mechanisms when combining a polyelectrolyte with a non-charged polymer are not trivial to pinpoint, these systems are generally poorly characterized in literature. Here, we attempt to provide a solid rationale to utilize PEG-PEI copolymers as surface modifiers and stabilizers/dispersion agents in solid colloidal systems with focus on biomedical applicability. EXPERIMENTAL: mPEG grafted PEI copolymers with two different grafting densities and 100 nm sized non-porous silica nanoparticles (SiNP) were synthesized. Detailed physico-chemical characterization of all prepared materials was conducted with spectroscopic methods, while the interaction mechanisms between the produced copolymers and SiNP were investigated by calorimetry. The influence of increased PEG grafting ratio on the attained colloidal stability of copolymer functionalized SiNP was studied by multiple light scattering, and its further implications on the biobehavior of SiNP were evaluated. FINDINGS: The interaction mechanism between SiNP and copolymers was concluded to be mainly directed by electrostatics, whereas an influence of PEG grafting density on the adsorption process was also observed. The implications of the surface modifications on the in vitro biobehavior of SiNP were investigated by combining the knowledge obtained by the detailed characterizations with microscopy evaluation under in vitro conditions.

Combination of magnetic field and surface functionalization for reaching synergistic effects in cellular labeling by magnetic core-shell nanospheres.

Aimed at utilizing high-magnetization nanospheres for magnetic field-enhanced cellular labeling, core-shell structured sandwich-like magnetic mesoporous silica nanospheres were developed. While the magnetite cluster core can provide a high magnetic response for overcoming Brownian motion in cell culture media, the layered silica shell facilitates an efficient fluorescent dye labeling. However, the problem of particle aggregation in cell media, which is strongly enhanced under a magnetic field, significantly impeded the uptake by cells, resulting in difficulties in the precise analysis of the degree of particle internalization by fluorescence-based techniques (flow cytometry and confocal microscopy). To overcome this, reflection-based assessment was employed. Further, emphasis was put on utilizing the unique role of surface-hyperbranched polyethylenimine (PEI) in efficient prevention of particle aggregation prior to cell internalization in the presence of an external magnetic field. The interparticle attraction forces originating from magnetic dipole-dipole interactions are hereby balanced by the steric and electrostatic repulsion forces provided by the PEI functionalization, which leads to dispersed nanospheres in cell culture media during the magnetic-field induced cell labeling. As a consequence, PEI functionalization and the presence of the magnetic field synergistically enhanced the efficiency of MRI-fluorescence dual-mode labeling for cellular tracking.