Current Organizations / Institutes

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Alina Stefanache has a total of 131 co-authors. Here are the top co-authors by number of shared publications:


Latest Publications

  • Open Access

    Design and Characterization of Cu(II), Ni(II), and Co(II) Complexes with 5-Carboxy-2-Thiouracil: Spectroscopic, Antimicrobial and Cytotoxic Studies

    by Miroslava Strandzheva, Petya Marinova, Dimitar Stoitsov, Alina Stefanache, Nikola Burdzhiev, Denica Blazheva, Aleksandar Slavchev, Evelina Varbanova, Ionut-Iulian Lungu, Yana Feodorova, et al.

    In this paper, we describe and verify the structures and biological activity of novel metal complexes derived from 5-carboxy-2-thiouracil. We outline a synthesis method and assess the antimicrobial activity of newly formed Cu(II), Ni(II) and Co(II) complexes. Several syntheses were carried out with and without NaOH. The structures were verified using melting point analysis, MP-AES for Cu, Ni and Co and ICP-OES for sulfur, UV-Vis, ATR, solid-state and solution 1H NMR, 13C NMR spectroscopy. In addition, the antimicrobial activity of these complexes and the free ligand were assessed against both Gram-positive and Gram-negative bacteria, as well as yeasts. The HCT-116 colorectal cell line (ATCC) was used for a cytotoxic assay. Only two Ni(II) complexes showed reduction in the number of viable tumor cells. None of the other compounds led to a significant reduction in the number of viable cells, as determined by one-way ANOVA statistical analysis.

  • Open Access

    Design and Characterization of Cu(II), Ni(II), and Co(II) Complexes with 5-Carboxy-2-Thiouracil: Spectroscopic, Antimicrobial and Cytotoxic Studies

    by Miroslava Strandzheva, Petya Marinova, Dimitar Stoitsov, Alina Stefanache, Nikola Burdzhiev, Denica Blazheva, Aleksandar Slavchev, Evelina Varbanova, Ionut Iulian Lungu, Yana Feodorova, et al.

    The aim of this paper is to obtain and verify the structures and the biological activity of novel metal complexes derived from 5-carboxy-2-thiouracil. The paper outlines a synthesis method and assesses the antimicrobial activity of newly formed Cu(II), Ni(II) and Co(II) complexes. Several syntheses were carried out with and without NaOH. The structural were verified by melting point analysis, ICP-OES for Cu, Ni and Co, UV-Vis, ATR, solid state and solution 1H NMR, 13C NMR spectroscopy. In addition, the antimi-crobial activity of these complexes and the free ligand are assessed against both Gram-positive and Gram-negative bacteria, as well as yeasts. For the cytotoxic assay we were used the HCT-116 colorectal cell line (ATCC). Only two Ni(II) complexes show reduction in the number of viable tumor cells. All the other compounds did not lead to a significant reduction in the number of viable cells as determined by one-way ANOVA statistical analysis.

  • Open Access

    Advanced Chitosan Biomacromolecular Platforms for Dental Biomedical Applications: A Bibliometric and Narrative Review of Chemical Functionalization, Bioactivity, and Therapeutic Potential

    by Mihnea Costescu, Liliana Gabriela Halitchi, Doina Spaiuc, Nicu Ovidiu Lungu, Alina Mitocaru, Andra Chelaru, Olga Odetta Duma, Carmen Stadoleanu, Delia Cristina Bahrim, Gabriela Calin, et al.

    Chitosan is a linear polysaccharide obtained by deacetylation of chitin, which is naturally present in the exoskeletons of crustaceans, insect cuticles, and the cell walls of certain fungi. Its favorable biological properties, combined with a highly adaptable chemical structure, have made it one of the most promising polymers for biomedical use. These attributes have enabled the development of diverse biomaterial platforms, including hydrogels, nanoparticles, nanofibers, scaffolds, membranes, implant coatings, and drug delivery systems tailored for oral and dental applications. The objective of this review is to highlight recent advances in chitosan-based biomaterials for modern dentistry by combining bibliometric analysis with insights into molecular engineering, chemical functionalization, and biomaterial fabrication. The literature search was conducted in the Scopus database using the query “chitosan AND dent”, with the bibliometric analysis covering publications indexed from 1989 to 2025. It examines how structural modifications influence the physicochemical and biological properties of chitosan, with particular emphasis on antimicrobial activity, biofilm management, tissue regeneration, osseointegration, remineralization, and controlled drug release. The discussion covers current applications in implantology, periodontics, endodontics, restorative dentistry, oral wound healing, and localized therapy. The bibliometric analysis revealed a marked increase in scientific output, particularly in recent years, alongside growing interest in multifunctional chitosan-based platforms for antimicrobial therapy, tissue regeneration, remineralization, and localized drug delivery. Future studies should prioritize standardized material characterization and manufacturing, long-term in vivo validation, and well-designed clinical trials to facilitate clinical translation. By integrating recent advances in chemical functionalization, biomaterial engineering, and oral biomedical applications, this review offers a comprehensive overview of advanced chitosan-based platforms and highlights current strategies for designing multifunctional biomaterials that enhance therapeutic performance.

  • Open Access

    Nanoformulations for Ocular Drug Delivery in Glaucoma: From Metal-Based Nanoparticles to Advanced Nanocarriers

    by Ionut Iulian Lungu, Liviu Stafie, Alina Stefanache, David-Constantin Stefan, Andreea Lungu, Georgiana-Elena Sarbu, Liliana Savin, Andreea Guraliuc, Francesca Cristiana Dohotariu, Nicoleta Anton

    Glaucoma is a chronic and progressive optic neuropathy in which sustained intraocular pressure (IOP) reduction remains the main therapeutic objective, while increasing attention is being directed toward neuroprotective strategies and improved ocular drug delivery. Conventional topical therapies are frequently limited by short precorneal residence time, poor ocular bioavailability, and the need for frequent administration. This narrative review examines nanoformulation-based strategies investigated for ocular drug delivery in glaucoma, ranging from metal-based nanoparticles, including gold, silver, zinc-, copper-, and iron-based systems, to advanced nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanosuspensions, dendrimers, cyclodextrin-based systems, and hydrogels. Particular attention is given to the relationship between nanocarrier composition, physicochemical characteristics, drug-loading and release properties, ocular retention and penetration, therapeutic effects, and the level of experimental evidence. The review further compares metal-based nanoparticles with non-metal-based nanocarriers, highlighting their respective advantages and limitations in terms of drug delivery, sustained ocular exposure, therapeutic potential, biocompatibility, toxicity, and translational relevance. Although several nanoformulation platforms have demonstrated promising results in preclinical studies, the available evidence remains heterogeneous and predominantly preclinical. Further research is needed to establish long-term ocular safety, optimize formulation characteristics, standardize evaluation methods, and determine the clinical relevance of these emerging delivery systems.

  • Open Access

    A Recent Review of the Therapeutic Potential of Gold, Platinum, and Ruthenium Complexes Combined with Certain Organic Compounds

    by Petya Marinova, Miroslava Strandzheva, Denica Blazheva, Ionut Iulian Lungu, Oana Cioanca, Monica Hancianu, Alina Stefanache

    The synthesis and systematic investigation of inorganic and organic compounds are fundamental to medicinal and pharmaceutical chemistry, particularly for developing novel therapeutic agents. Transition-metal complexes and bioactive organic compounds have shown significant potential to modulate cellular pathways, yielding anticancer, antimicrobial, and anti-inflammatory effects. This review summarizes recent advances in the synthesis, structural characterization, and therapeutic evaluation of gold (Au), platinum (Pt), and ruthenium (Ru) complexes, as well as selected organic compounds, with an emphasis on their biological activities and potential clinical relevance. The integration of synthetic chemistry with biological evaluation underscores the therapeutic potential of gold (Au), platinum (Pt), and ruthenium (Ru) complexes, as well as organic compounds. Au(I/III), Pt(II/IV), and Ru(II/III) complexes demonstrated notable in vivo anticancer activity, while selected organic derivatives exhibited promising bioactive properties. This review aims to support researchers and clinicians in the ongoing development of novel compounds with clinical relevance for anticancer, antimicrobial, and anti-inflammatory applications.

  • Open Access

    Dietary exposure to food additives in ultra-processed foods: implications for gut microbiome, metabolic health, and risk assessment

    by Corina Dalia Toderescu, Elena Narcisa Narcisa Pogurschi, Alina Stefanache, Melania Florina Munteanu, Svetlana Trifunschi, Alexandru Oancea, Meda-Ada Bugi, Iulia Cresneac

    Background: The increasing consumption of ultra-processed foods has led to a substantial rise in dietary exposure to food additives, making them a consistent component of modern dietary patterns. While food additives are generally considered safe within established regulatory limits, their long-term health effects remain a subject of growing scientific interest, particularly from a nutritional epidemiology perspective. Methods: This narrative review, conducted following PRISMA-informed principles, synthesizes recent experimental, clinical, and epidemiological evidence on the health effects of major food additive categories, including emulsifiers, non-nutritive sweeteners, preservatives, and synthetic colorants. Literature searches were performed in Web of Science, Scopus, and PubMed, covering studies published between 2010 and 2024. A qualitative assessment of study quality was performed based on study design, sample size, and potential sources of bias. The results of this assessment are summarized in Table 2 . Results: Dietary exposure to food additives through ultra-processed foods has been associated with changes in the gut microbiome, metabolic function, and low-grade inflammation. Experimental studies consistently report biological effects, particularly for emulsifiers and artificial sweeteners, whereas epidemiological findings remain heterogeneous and influenced by overall dietary patterns. Conclusion: Current evidence supports the need to evaluate food additives within the context of dietary patterns rather than as isolated compounds. While most approved additives remain safe at regulated intake levels, emerging data suggest that cumulative exposure and diet–microbiome interactions may not be fully captured by existing risk assessment frameworks. Integrating nutritional context into future safety evaluations may improve their relevance for public health.


  • Open Access

    Natural Polymers in Tissue Engineering and Regeneration: Material–Cell Mechanotransduction, Biofabrication Strategies, and Clinical Translation

    by Gabriela Calin, Mihnea Costescu, Marcela Nour, Camer Salim, Nicu Ovidiu Lungu, Alina Stefanache, Roman Rusnac, Elena Costescu, Mihai Cozmin, Petruta Iuliana Moraru, et al.

    Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make current grafting techniques less effective. Biomaterials that come from nature, like collagen, gelatin, chitosan, alginate, hyaluronic acid (HA), and silk fibroin, have become promising scaffolds because they are bioactive, mimic the extracellular matrix (ECM), and can be broken down by enzymes. Crosslinking and composite reinforcement can greatly change how well they work. For example, collagen scaffolds that are highly crosslinked with glutaraldehyde keep up to 51.9% of their tensile strength after being exposed to enzymes, while non-crosslinked scaffolds only keep 12% of their strength. Chitosan–hydroxyapatite matrices, on the other hand, can reach compressive strengths of 2–12 MPa, which is close to the strength of cancellous bone. Additive manufacturing and 4D printing allow for precise control of structures and the ability to change their shape over time, which helps with vascularization and mechanical adaptation. Injectable and in situ-forming hydrogels show clinically important results, such as filling 85% of osteochondral defects in rabbits, improving left ventricular ejection fraction by up to 9% in large-animal cardiac models, and speeding up healing by 25–40% in chronic wounds. Even with these improvements, it is still hard to get batch consistency, a standardized way to test mechanical properties, and production that meets GMP (Good Manufacturing Practices) standards and can be scaled up.


  • Top Cited Papers
    Open Access

    Green-Synthesized Copper and Copper Oxide Nanoparticles: Structural Characterization and Evaluation of Biological Activity

    by Ionut Iulian Lungu, Alina Stefanache, Nicoleta Anton, Andreea Lungu, Vera-Maria Platon, Andreea-Maria Mitran, Oana Cioanca, Cornelia Mircea, Monica Hancianu

    Copper-based nanoparticles, especially metallic copper (Cu NPs) and copper oxide (CuO NPs), have attracted increasing attention due to their redox activity, biological efficacy, and technological applications. However, conventional chemical synthesis often involves toxic reagents, limiting their biomedical applicability. In this context, plant-mediated green synthesis has evolved and has become a sustainable and cost-effective alternative. This review provides a comprehensive overview of recent advances in the biosynthesis of Cu and CuO nanoparticles using plant extracts. The main synthesis pathways are examined, with emphasis on the role of phytochemicals as reducing, stabilizing, and capping agents, as well as the influence of reaction parameters on nanoparticle yield. The review highlights the diversity of plant species and extract types used and clarifies their effects on nanoparticle size, morphology, oxidation state, and surface chemistry. Key physicochemical characterization techniques (ultraviolet–visible (UV–Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), electron microscopy, and zeta potential analysis) are systematically discussed. Moreover, a summary of in vitro and in vivo biological activities is provided, including antimicrobial, antioxidant, cytotoxic, anticancer, wound-healing, and plant-growth-promoting effects. Overall, plant-mediated copper-based nanoparticles demonstrate significant potential as biofunctional nanomaterials. Nevertheless, challenges concerning reproducibility, mechanistic understanding, standardization and toxicological evaluation must be addressed to facilitate reliable translation into biomedical applications.


  • Open Access

    Intranasal Drug Delivery in Neuropharmacology: Advances in Brain-Targeted Therapies and Bioethical Challenges

    by Simona Irina Damian, Sofia Mihaela David, Marcela Nour, Gabriela Liliana Halitchi, Sorina Alexandra Ciurlea, Alina Stefanache, Olga-Odetta Duma, Gabriela Calin, Doina Spaiuc

    Intranasal drug delivery represents a transformative “backdoor” to the brain, bypassing the blood–brain barrier (BBB) that bars 98% of small molecules and nearly all large biopharmaceuticals. By harnessing the unique anatomy of the olfactory and trigeminal nerves, therapeutics can travel directly from the nasal cavity to the central nervous system, achieving therapeutic concentrations without the systemic toxicity of traditional routes. Clinical and preclinical evidence highlight the efficacy of intranasal insulin (INI) in treating Alzheimer’s disease (AD) and delirium, with studies showing significant improvements in cognitive scores and reduced hospital stays (7.9 vs. 12.9 days; p = 0.014). Additionally, other peptides can be administered intranasally like oxytocin, neuropeptide Y, and novel metabolic modulators for neuroprotection and affective disorders (AD, autism, Down syndrome). Despite these promises, critical translational gaps remain, including anatomical differences between macrosmatic rodents and microsmatic humans, and significant sex-based dosing dimorphism. The ease of intranasal administration introduces profound bioethical dilemmas regarding neuroenhancement, authenticity, and informed consent in vulnerable populations. The current literature concludes that realizing the full potential of nose-to-brain (N2B) therapy requires a commitment to precision medicine, utilizing specialized delivery devices and objective biomarkers to ensure safe and equitable clinical application.


  • Top Cited Papers
    Open Access

    Dietary Polyphenols as Modulators of Bifidobacterium in the Human Gut Microbiota

    by Corina Dalia Toderescu, Mohamudha Parveen, Svetlana Trifunschi, Alexandru Oancea, Gentiana Camelia Ciubuc (Jurj), Iulia Gabriela Cresneac, Melania Florina Munteanu, Ioana Ciopanoiu, Casiana Boru, Elena Narcisa Pogurschi, et al.

    Background: Polyphenols—bioactive compounds abundant in plant-based foods—are increasingly recognised for their capacity to modulate the gut microbiota. As the gut microbiome plays a central role in metabolic regulation, immune function, and disease prevention, understanding how specific polyphenol subclasses influence microbial diversity and functionality remains essential. Despite growing evidence of their benefits, the precise effects of flavonoids, phenolic acids, and anthocyanins on gut microbial composition are not yet fully clarified. Objective: This study aimed to evaluate the impact of dietary polyphenols on gut microbiota composition and function, with a particular focus on the abundance of Bifidobacterium, a key beneficial genus associated with metabolic and immune health. It was hypothesised that polyphenol-rich interventions were associated with increases in Bifidobacterium abundance and enhance overall microbial diversity. Design: A systematic review and meta-analysis were conducted following PRISMA guidelines. Human intervention studies published between January 2015 and February 2025 were retrieved from PubMed, Scopus, and Web of Science. A predefined PICO framework guided study selection. Twenty-two studies were synthesised using thematic analysis, and four of these were eligible for quantitative meta-analysis. The meta-analysis was performed in R (version 4.4.1) using the metafor and meta packages, calculating standardised mean differences (SMD) under a random-effects model to account for heterogeneity. Extracted data included study design, population characteristics, polyphenol subclass, intervention type, microbiome assessment method, and key outcomes. Results: Across the 22 reviewed studies, polyphenols—particularly flavonoids and phenolic acids from foods such as berries, grape pomace, and green tea—consistently increased beneficial microbial taxa including Bifidobacterium, Faecalibacterium, and Lactobacillus. These microbial shifts were associated with improved metabolic markers, reduced inflammation, and enhancements in gut barrier integrity. Polyphenol-rich dietary patterns also showed benefits in conditions such as NAFLD, prediabetes, and depression. However, findings were influenced by interindividual variability, short intervention durations, and inconsistent methodologies. The meta-analysis revealed a significant positive effect of polyphenol intake on Bifidobacterium abundance (SMD = 0.81; 95% CI: 0.18–1.44; p = 0.0114), corresponding to a moderate-to-large effect size. Substantial heterogeneity (I2 = 77.4%) suggested considerable variation in intervention types, dosage, study design, and microbiome analysis methods. Conclusions: Polyphenol-rich diets were associated with increased Bifidobacterium abundance and favourable modulation of gut microbiota composition, supporting their potential as a nutritional strategy to enhance gut and metabolic health. However, interstudy variability highlights the need for more standardised, long-term, and mechanistically focused human trials. Future research should incorporate multi-omics approaches, personalised nutrition frameworks, and consistent microbiome analysis methods to better understand the pathways linking polyphenol intake and host health outcomes.