Cosmin Mihai
Research Scientist II - Biologie Experimentală și Aplicată
Publications
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article
Comparative In Vitro Study Between Biocompatible Chitosan-Based Magnetic Nanocapsules And Liposome Formulations With Potential Application In Anti-Inflammatory Therapy |
Vochita Gabriela; Cadinoiu Anca Niculina; Rata Delia-Mihaela; Atanase Leonard Ionut; Popa Marcel; Mahdieh Athar; Mihai Cosmin-Teodor; Stache Alexandru-Bogdan; Moldovan Cristina-Veronica; Bacaita Elena Simona; Condriuc Iustina Petra; Gherghel Daniela | International Journal Of Molecular Sciences, 2024 | |
AbstractThis study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 mu g/mL) and 76.37% (OCNPM-1, 25 mu g/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 mu g/mL) and 75.15% (OCNPM-3, 25 mu g/mL) at the highest dose (25 mu g/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 mu g/mL) and 58.20% (CLDMM2CP-1 1.25 mu g/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy. |
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article
In vitro cytophysiological response induced by three food additives on some mammalian cell line models |
Gherghel D., Mihai C.-T., Vochita G., Rosu C. M. | Journal of Experimental and Molecular Biology, 2024 | |
AbstractThis research is focused on cellular response to sodium metabisulphite (E223), sodium benzoate (E211), and sodium nitrite (E250) application on two normal mammalian cells, namely MCF-12A (ATCC CRL-3598) and Vero (ATCC CCL-81). The monitored parameters were cell viability (MTT assay), cell morphology (optical microscopy) and cell survival (clonogenic assay). The treatment was applied in doses of 12.5; 25; 50 and 100 µg/mL. According to all tests assessed, our results proved a dose-response relationship, the most sensibility presented the MCF-12A cell line. |
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article
Peptide-Functionalized Chitosan-Based Microcapsules For Dual Active Targeted Treatment Of Lung Infections |
Rata Delia Mihaela; Cadinoiu Anca Niculina; Atanase Leonard Ionut; Popa Marcel; Mihai Cosmin Teodor; Vochita Gabriela | International Journal Of Biological Macromolecules, 2024 | |
AbstractLung infections, such as: pneumonia, chronic obstructive cystic fibrosis, tuberculosis are generally caused by viruses, bacteria and fungi. As these infections are very difficult to treat, new therapeutic approaches are investigated in order to maximize the efficiency of the treatment and to reduce the major complications that can occur. The main objective of this study was focused on the preparation of drug-loaded peptides-functionalized microcapsules, obtained by a double emulsion, based on carboxylated chitosan (CMCS), poly(vinyl alcohol) (PVA) and an activator [4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride] (DMT-MM), for the dual active targeting and treatment of pulmonary infections. The microcapsules were functionalized on the surface with both CGSPGWVRC and indolicidin (IN) peptides, as effective ligands for the active targeting of both alveolar capillary endothelial cells and bacterial cells. FTIR spectroscopy confirmed the formation of ester and amide bonds into the structure of prepared microcapsules. Microcapsules diameter varied between 893 and 965 nm. The swelling degree in PBS, at pH 7.4, ranged between 1760 %- 2100 %. All the analyzed samples showed hemolysis degrees lower than 2 %, which demonstrated their non-hemolytic character. Evaluation of the impact of microcapsules on WI-38 normal human lung cells and RAW 264.7 mouse macrophages revealed a non-toxic or slightly cytotoxic effect. Internalization assay proved that microcapsules were localized at intracellular level. |
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article
Α-Chitosan And Β-Oligochitosan Mixtures-Based Formula For In Vitro Assessment Of Melanocyte Cells Response |
Schroder Verginica; Gherghel Daniela; Apetroaei Manuela Rossemary; Gijiu Cristiana Luminita; Isopescu Raluca; Dinculescu Daniel; Apetroaei Miruna-Maria; Enache Laura Elena; Mihai Cosmin-Teodor; Rau Ileana; Vochita Gabriela | International Journal Of Molecular Sciences, 2024 | |
AbstractChitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma, and indicates that these molecules can open new perspectives on antiproliferative action and anticancer therapy. This study analyzes how different chitosan conformations, such as alpha-chitosan (CH) or beta-oligochitosan (CO), with various degrees of deacetylation (DDA) and molar mass (MM), both in different concentrations and in CH-CO mixtures, influence the cellular processes of SK-MEL-28 melanocytes, to estimate the reactivity of these cells to the applied treatments. The in vitro evaluation was carried out, aiming at the cellular metabolism (MTT assay), cellular morphology, and chitinase-like glycoprotein YKL-40 expression. The in vitro effect of the CH-CO mixture application on melanocytes is obvious at low concentrations of alpha-chitosan/beta-oligochitosan (1:2 ratio), with the cell's response supporting the hypothesis that beta-oligo-chitosan amplifies the effect. This oligochitosan mixture, favored by the beta conformation and its small size, penetrates faster into the cells, being more reactive when interacting with some cellular components. Morphological effects expressed by the loss of cell adhesion and the depletion of YKL-40 synthesis are significant responses of melanocytes. beta-oligochitosan (1.5 kDa) induces an extension of cytophysiological effects and limits the cell viability compared to alpha-chitosan (400-900 kDa). Statistical analysis using multivariate techniques showed differences between the CH samples and CH-CO mixtures. |
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article
Cold Atmospheric Plasma, Platelet-Rich Plasma, And Nitric Oxide Synthesis Inhibitor: Effects Investigation On An Experimental Model On Rats |
Caba Bogdan; Gardikiotis Ioannis; Topala Ionut; Mihaila Ilarion; Mihai Cosmin Teodor; Luca Catalina; Pasca Sorin; Caba Ioana Cezara; Dimitriu Gabriel; Huzum Bogdan; Serban Ionela Lacramioara | Applied Sciences-Basel, 2022 | |
AbstractFeatured Application Potential use in flap surgery, towards growing flap viability, diminishing marginal, or partial flap necrosis, as well as shortening the waiting period for angiogenesis in pedicled or tubulised flaps before second stage reconstruction. The evolution of reconstructive methods for defects of the human body cannot yet replace the use of flap surgery. Research is still preoccupied with the ideal techniques for offering the best chances of survival of the flaps. In our study, we investigated the effects of cold atmospheric plasma (CAP), N-nitro-L-arginine methyl ester (L-NAME), and platelet-rich plasma (PRP) injectable solutions on flap survival using an in vivo model. Twenty-four Wistar rats (four groups) had the McFarlane flap raised and CAP, L-NAME, and PRP substances tested through a single dose subcutaneous injection. The control group had only a saline solution injected. To the best of our knowledge, this is the first study that evaluated a CAP activated solution through injection on flaps. The flap survival rate was determined by clinical examination (photography documented), hematology, thermography, and anatomopathological tests. The image digital analysis performed on the flaps showed that the necrosis area (control-49.64%) was significantly lower for the groups with the three investigated solutions: CAP (14.47%), L-NAME (18.2%), and PRP (23.85%). Thermography exploration revealed less ischemia than the control group on the CAP, L-NAME, and PRP groups as well. Anatomopathological data noted the best degree of angiogenesis on the CAP group, with similar findings on the L-NAME and PRP treated flaps. The blood work did not indicate infection or a strong inflammatory process in any of the subjects. Overall, the study shows that the CAP activated solution has a similar (better) impact on the necrosis rate (compared with other solutions with known effects) when injected on the modified dorsal rat skin flap, and on top of that it can be obtained fast, in unlimited quantities, non-invasively, and through a standardized process. |
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article
Biotinylated Chitosan Macromolecule Based Nanosystems: A Review From Chemical Design To Biological Targets |
Balan V.; Dodi G.; Mihai C. T.; Serban A. M.; Ursachi V. C. | International Journal Of Biological Macromolecules, 2021 | |
AbstractWorld Health Organization estimates that 30-50% of cancers are preventable by healthy lifestyle choices, early detection and adequate therapy. When the conventional therapeutic strategies are still regulated by the lack of selectivity, multidrug resistance and severe toxic side effects, nanotechnology grants a new frontier for cancer management since it targets cancer cells and spares healthy tissues. This review highlights recent studies using biotin molecule combined with functional nanomaterials used in biomedical applications, with a particular attention on biotinylated chitosan-based nanosystems. Succinctly, this review focuses on five areas of recent advances in biotin engineering: (a) biotin features, (b) biotinylation approaches, (c) biotin functionalized chitosan based nanosystems for drug and gene delivery functions, (d) diagnostic and theranostic perspectives, and (e) author's inputs to the biotin-chitosan based tumour-targeting drug delivery structures. Precisely engineered biotinylated-chitosan macromolecules shaped into nanosystems are anticipated to emerge as next-generation platforms for treatment and molecular imaging modalities applications. |
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article
Cytotoxic Effect Of Chloroform Extracts From Tanacetum Vulgare, T. Macrophyllum And T. Corymbosum On Hela, A375 And V79 Cell Lines |
Ivanescu Bianca; Pop Carmen Elena; Vlase Laurian; Corciova Andreia; Gherghel Daniela; Vochita Gabriela; Tuchilus Cristina; Mardari Constantin; Teodor Cosmin Mihai | Farmacia, 2021 | |
AbstractThe effect of Tanacetum extracts on cell viability was assessed by MTT method on HeLa (human cervical epithelioid carcinoma), A375 (human malignant melanoma) and V79 (Chinese hamster pulmonary fibroblasts). Apoptosis, cell cycle analysis, and genotoxicity tests were performed to identify the possible mechanism of action. Also, the antimicrobial activity was investigated, and LC-MS analysis of extracts was carried out. Tanacetum extracts substantially reduced the viability of all tested cells, normal cells being more sensitive than cancer cells. T. vulgare and T. macrophyllum extracts induced apoptosis in normal cells V79, while none of the extracts induced apoptosis on HeLa or A375 neoplastic cells. T. vulgare extract arrested cell cycle progression of V79 and A375 cells at the G(2)/M phase and exhibited mild genotoxicity on melanoma cells A375. All extracts showed moderate antimicrobial activity against tested Gram-positive bacteria and fungi. |
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article
Cytotoxic activity of Pinus cembra L. needle extract: A preliminary study on HeLa cell line. |
Lungu C., Mihai C.-T., Vochita G., Gherghel D., Miron S.-D., Aprotosoaie A.C., Miron A. | Romanian Journal of Pharmaceutical Practice, 2021 | |
AbstractThe aim of this study was to investigate the cytotoxic effects of a hydromethanolic extract obtained from cembran pine needles in HeLa cell line. In this respect, the effects of needle extract on protein synthesis, viability, proliferation and cell cycle in HeLa cells were evaluated after 48 h treatment. Cembran pine needle extract dose-dependently decreased protein synthesis in HeLa cells causing 44.26% reduction in protein synthesis at 100µg/ml. At 25, 50 and 100µg/ml, it increased cell death in comparison with the control (20.99%, 21.49% and 23.63%, respectively vs. 9.83%). In addition, at 100µg/ ml, cembran pine needle extract showed a remarkable antiproliferative effect whereas at 25 and 50µg/ml, it induced sub-G1 phase cells accumulation (11.68 ± 0.81% and 14.69 ± 0.56%, respectively in comparison with control, 6.03 ± 0.55%), an indicator of proapoptotic effects. Taken together, these results indicate that cembran pine needles are a source of compounds with antitumor potential which needs to be further investigated and exploited |
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article
Formulations Based On Drug Loaded Aptamer-Conjugated Liposomes As A Viable Strategy For The Topical Treatment Of Basal Cell Carcinoma-In Vitro Tests |
Cadinoiu Anca N.; Rata Delia M.; Atanase Leonard I.; Mihai Cosmin T.; Bacaita Simona E.; Popa Marcel | Pharmaceutics, 2021 | |
AbstractTopical liposomal drug formulations containing AS1411-aptamer conjugated liposomes were designed to deliver in a sustained way the 5-fluorouracil to the tumor site but also to increase the compliance of patients with basal cell carcinoma. The 5-fluorouracil penetrability efficiency through the Strat-M membrane and the skin irritation potential of the obtained topical liposomal formulations were evaluated in vitro and the Korsmeyer Peppas equation was considered as the most appropriate to model the drug release. Additionally, the efficiency of cytostatic activity for targeted antitumor therapy and the hemolytic capacity were performed in vitro. The obtained results showed that the optimal liposomal formulation is a crosslinked gel based on sodium alginate and hyaluronic acid containing AS1411-aptamer conjugated liposomes loaded with 5-fluorouracil, which appeared to have favorable biosafety effects and may be used as a new therapeutic approach for the topical treatment of basal cell carcinoma. |
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article
In Vitro Anticancer Activity And Oxidative Stress Biomarkers Status Determined By Usnea Barbata (L.) Fh Wigg. Dry Extracts |
Popovici Violeta; Bucur Laura; Vochita Gabriela; Gherghel Daniela; Mihai Cosmin Teodor; Rambu Dan; Calcan Suzana Ioana; Costache Teodor; Cucolea Iulia Elena; Matei Elena; Badea Florin Ciprian; Caraiane Aureliana; Badea Victoria | Antioxidants, 2021 | |
AbstractLichens represent an important resource for common traditional medicines due to their numerous metabolites that can exert diverse pharmacological activities including anticancer effects. To find new anticancer compounds with fewer side effects and low tumor resistance, a bioprospective study of Usnea barbata (L.) F.H. Wigg. (U. barbata), a lichen from the Calimani Mountains (Suceava county, Romania) was performed. The aim of this research was to investigate the anticancer potential, morphologic changes, wound healing property, clonogenesis, and oxidative stress biomarker status of four extracts of U. barbata in different solvents (methanol, ethanol, acetone, and ethyl acetate), and also of usnic acid (UA) as a positive control on the CAL-27 (ATCC(R) CRL-2095 (TM)) oral squamous carcinoma (OSCC) cell line and V79 (ATCC(R) CCL-93 (TM)) lung fibroblasts as normal cells. Using the MTT assay and according to IC50 values, it was found that the most potent anticancer property was displayed by acetone and ethyl acetate extracts. All U. barbata extracts determined morphological modifications (losing adhesion capacity, membrane shrinkage, formation of abnormal cellular wrinkles, and vacuolization) with higher intensity in tumor cells than in normal ones. The most intense anti-migration effect was established in the acetone extract treatment. The clonogenic assay showed that some U. barbata extracts decreased the ability of cancer cells to form colonies compared to untreated cells, suggesting a potential anti-tumorigenic property of the tested extracts. Therefore, all the U. barbata extracts manifest anticancer activity of different intensity, based, at least partially, on an imbalance in antioxidant defense mechanisms, causing oxidative stress. |
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