The below list represents only planned manuscripts. Some of these
manuscripts have not been received by the Editorial Office yet. Papers
submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: Nanoparticle mediated pulmonary drug delivery - a review
Authors: Mukta Paranjpe and Christel C. Müller-Goymann
Abstract: Colloidal drug delivery systems have been extensively investigated as drug carrier systems for the application of different drugs via different routes of administration. Solid lipid nanoparticles (SLN) are one the most interesting colloidal systems studied since more than a decade. SLN are aqueous nanoscale suspensions prepared mainly from lipids and triglycerides of physiological tolerability. The pulmonary route is now attaining popularity owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API) forming an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages over conventional per oral administration such as high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect as well as the avoidance of degrading conditions in the GI tract. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. As SLN are prepared from phospholipids which are a physiological part of lung tissue, they have low toxicity. Also, the surfactant associated proteins present at the interface enhances the effect of these phospholipid containing formulations by decreasing the surface tension and allowing maximum effect. The following review focuses on current status of different colloidal systems available for the treatment of various lung disorders, manufacturing processes of various colloidal nanosystems and their characterization. As well as different in vitro ,ex vivo and in vivo cell models developed for testing of these systems with studies involving cell culture analysis are also discussed.
Keywords: Nanoparticles, SLN, toxicity, lung cell models, aerosol, nebulization, lung disease
Title: Remediated titania nanoparticles to reduce lung exposure at work places: an in vitro study
Authors: Lucia Migliore1, Sebastiano Di Bucchianico1, Chiara Uboldi1, Magda Blosi2, Camilla Delpivo2, Anna Costa2.
Affiliation: 1University of Pisa, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa, Italy; 2 National Research Council of Italy, Institute of Science and Technology for Ceramics, Faenza, Italy.
Email for contact: firstname.lastname@example.org
Abstract: To circumvent the cytotoxic and genotoxic effects potentially exerted by nanoparticles (NPs) on the human health and to enhance a safe occupational exposure scenario, we have applied a risk remediation strategy based on the “safe-by-design” concept. For this reason, titanium dioxide nanoparticles (TiO2-NPs) were alternatively coated with silica and with citrate, and their toxicological profile has been compared to the uncoated NPs in a human lung epithelial cell line, A549.
By the non-colorimetric Colony Forming Efficiency (CFE) assay we have observed that silicated TiO2-NPs resulted less cytotoxic to A549 cells than uncoated and citrated titania. Similarly, by CBMN cytome assay citrated NPs resulted the most cytotoxic, cytostatic and genotoxic to A549 cells, while silica-coated TiO2-NPs enhanced the proliferation by reducing apoptosis and chromosomal aberrations, this last evaluated by scoring micronuclei, nuclear buds and nucleoplasmic bridges.
Currently we are performing comet assay to evaluate primary and oxidative DNA damage induced by titania, and fluorescence in situ hybridization (FISH) to discriminate between clastogenic and aneuploidogenic effects of differently coated TiO2-NPs.
In conclusion, this study indicates that surface coating, among other physico-chemical properties of NPs such as size, surface area and charge, plays a pivotal role in determining the biocompatibility and the safety of NPs, highlighting the importance of the “safe-by-design” concept at work places to minimize the occupational exposure.
Title: Computational Prediction of Nanotoxicity
Authors: Suresh Panneerselvam and Sangdun Choi
Affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea
Abstract: Nanotechnology has emerged as a key player in the field of nanomedicine. The engineered nanoparticles are deluged and the safety assessment is substantial in the therapeutic applications of new nanomaterials. Since the experimental evaluation of nanomaterials is expensive, the computational approaches are promising for predicting the toxicity. With the availability of high computing power the prediction of nanomaterials properties can be helpful to understand their adverse effects. This review highlights the recent works on computational approaches for nanomaterials such as quantitative structure activity relationship (QSAR), molecular dynamics (interaction of nanoparticles with proteins) and bioinformatics (data management). In addition, the examples of system biology approaches to nanomedicine will be addressed.
Title: Carbon Nanotube-Induced Pulmonary Granulomatous Disease: Twist1 and Alveolar Macrophage M1 Activation
Authors: Barbara P. Barna1, Isham Huizar2, Anagha Malur1, Matthew McPeek, Irene Marshall, Mark Jacob, Mani S. Kavuru3, and Mary Jane Thomassen1
Abstract: Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to several environmental risk factors, among which are some that may favor carbon nanotube formation. Using gene array data, we initially observed that bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed significantly elevated mRNA of the transcription factor, Twist1, among many M1-associated genes compared to healthy controls. Based on this observation we hypothesized that Twist1 mRNA and protein expression might become elevated in alveolar macrophages from animals bearing granulomas induced by carbon nanotube instillation. To address this hypothesis, wild-type C57Bl/6 and macrophage-specific PPAR null mice were given oropharyngeal instillation of multiwall carbon nanotubes (MWCNT). BAL cells obtained 60 days later exhibited significantly elevated Twist1 mRNA expression in granuloma-bearing wild-type or PPAR null alveolar macrophages compared to sham controls. Overall, Twist1 expression levels in PPAR null mice were higher than those of wild-type. Concurrently, BAL cells obtained from sarcoidosis patients and healthy controls validated gene array data: qPCR and protein analysis showed significantly elevated Twist1 in sarcoidosis compared to healthy controls. In vitro studies of alveolar macrophages from healthy controls indicated that Twist1 was inducible by classical (M1) macrophage activation stimuli (LPS, TNFα) but not by IL-4, an inducer of alternative (M2) macrophage activation. Findings suggest that Twist1 represents a PPAR-sensitive alveolar macrophage M1 biomarker which is induced by inflammatory granulomatous disease in the MWCNT model and in human sarcoidosis.