A Preliminary Report Regarding the Morphological Changes of Nano-Enabled Pharmaceutical Formulation on Human Lung Carcinoma Monolayer and 3D Bronchial Microtissue
Cătălin Prodan-Bărbulescu,
Claudia-Geanina Watz,
Elena-Alina Moacă,
Alexandra-Corina Faur,
Cristina-Adriana Dehelean,
Flaviu Ionut Faur,
Laura Octavia Grigoriţă,
Anca Laura Maghiari,
Paul Tuţac,
Ciprian Duţă,
Sorin Bolintineanu,
Laura Andreea Ghenciu
Affiliations
Cătălin Prodan-Bărbulescu
Department I—Discipline of Anatomy and Embryology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Claudia-Geanina Watz
Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Elena-Alina Moacă
Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Alexandra-Corina Faur
Department I—Discipline of Anatomy and Embryology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Cristina-Adriana Dehelean
Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Flaviu Ionut Faur
Department X—Discipline of Surgery II, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Laura Octavia Grigoriţă
Department I—Discipline of Anatomy and Embryology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Anca Laura Maghiari
Department I—Discipline of Anatomy and Embryology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Paul Tuţac
Toxicology and Molecular Biology Department, “Pius Brinzeu” Clinical Emergency County Hospital, RO-300723 Timisoara, Romania
Ciprian Duţă
Department X—Discipline of Surgery II, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Sorin Bolintineanu
Department I—Discipline of Anatomy and Embryology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Laura Andreea Ghenciu
Department I—Discipline of Anatomy and Embryology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, RO-300041 Timisoara, Romania
Background and Objectives: Nowadays, the development of enabled pharmaceutical nanoparticles of solid lipid type is continuously growing, because they have the potential to be used for targeted drug release leading to an increased effect of chemotherapy, being used in lung cancer nano-diagnosis and nano-therapy. The current study reports the preliminary results obtained regarding the biological effect of a new nano-enabled pharmaceutical formulation in terms of its cytotoxic and biosafety profile. Materials and Methods: The pharmaceutical formulations consist of solid lipid nanoparticles (SLN) obtained via the emulsification–diffusion method by loading green iron oxide nanoparticles (green-IONPs) with a pentacyclic triterpene (oleanolic acid—OA). Further, a complex biological assessment was performed, employing three-dimensional (3D) bronchial microtissues (EpiAirwayTM) to determine the biosafety profile of the SLN samples. The cytotoxic potential of the samples was evaluated on human lung carcinoma, using an in vitro model (A549 human lung carcinoma monolayer). Results: The data revealed that the A549 cell line was strongly affected after treatment with SLN samples, especially those that contained OA-loaded green-IONPs obtained with Ocimum basilicum extract (under 30% viability rates). The biosafety profile investigation of the 3D normal in vitro bronchial model showed that all the SLN samples negatively affected the viability of the bronchial microtissues (below 50%). As regards the morphological changes, all the samples induce major changes such as loss of the surface epithelium integrity, loss of epithelial junctions, loss of cilia, hyperkeratosis, and cell death caused by apoptosis. Conclusions: In summary, the culprit for the negative impact on viability and morphology of 3D normal bronchial microtissues could be the too-high dose (500 µg/mL) of the SLN sample used. Nevertheless, further adjustments in the SLN synthesis process and another complex in vitro evaluation will be considered for future research.
