BrainMap

Mr. Ioan Tomuta

PhD

Professor - UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Researcher | Teaching staff | Scientific reviewer | Consultant | PhD supervisor

Web of Science ResearcherID: B-8433-2011

Curriculum Vitae (16/04/2024)

Expertise & keywords

Expert System based on Artificial Neural Network for 3D-Printability Prediction of Tailored Release Oral Dosage Forms Call name: P 4 - Proiecte de cercetare exploratorie - PCE-2021
PN-III-P4-PCE-2021-1119 2022 - 2024

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://www.expertsystem.3dprinting-drugs.com

Abstract:

This project aims to create an expert system based on artificial intelligence for predicting the printing capacity of active substances, in order to prepare personalized pharmaceutical products by 3D printing (3DP). The expert system relies on a database consisting of the characteristics of active substances from different biopharmaceutical classes, the characteristics of the extruded filaments with different API loads and of the printed products. The polymer chosen for printing is polyvinyl alcohol, as such or in combination with plasticizers. Briefly, the substances selected upon a rigorous molecular and physical-chemical characterization will be used for the hot-melt extrusion of polymeric filaments, and after characterization, the filaments will be subjected to printing by fused deposition modelling, followed by the evaluation of the prints. The Design of Experiments method will be used for the study of filaments and prints, multivariate analysis to create multivariate correlations between input and output variables, followed by modelling of algorithms by artificial neural networks (ANNs) capable of predicting the printing capacity of other drugs based on the obtained models. The ANN trained algorithms further integrated into a user-friendly web interface (the Drug3DPrintExpert) will be validated on new active substances and made available for the scientific community and drug producers interested in preparing pharmaceutical drug products by 3DP.

Pharmaceutical development of a gastroretentive floating drug delivery system manufactured by 3D printing Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2021-3370 2022 - 2024

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://www.3dp-grfdds.3dprinting-drugs.com

Abstract:

The three dimensional printing (3DP) technology integration into the pharmaceutical field was taken into consideration in the pursuit to improve quality with the concomitant enabling of therapy personalization. The notion of 3DP includes a wide variety of technologies, fused deposition modelling (FDM) constituting a preferred representative of the group, due to its versatility and cost-effectiveness.

The integration of 3DP-FDM in pharmaceutics, up to this point, shows promising results. The technology besides material and process considerations, introduces the notion of design in the overall quality equation. By enabling design modulation, dissolution may be adapted achieving personalization and also production may be simplified for products with special design needs, like low density reliant gastro-retentive drug delivery systems (GRDDS).

The scope of the project will be to produce 3D printed gastroretentive floating drug delivery system (3DP-GRFDDS). Complex products will be aimed that combine the particularities of immediate release (IR) and prolonged release (PR) within the same dosage form by employing two different drug delivery mechanisms. The sustained release profile will be achieved through material and design considerations, by having an IR compartment with rapid disintegration and a PR floating compartment with prolonged gastric retention. Biopharmaceutically challenged active pharmaceutical ingredients (APIs) will be selected, that benefit from both sustained release and gastric retention. Due to the novelty of the methodology, the development will be done based on the quality by design premises, ultimately aiming to explain the combined and individual effects of material, technology and design considerations on 3DP product quality.

Development of siRNA pharmaceutical nanosystems for colonic gene silencing Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-0736 2022 - 2024

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://devrnanscoldh.wordpress.com

Abstract:

The main objective of this project is to develop a nanometric pharmaceutical system with the ability to improve the efficiency of siRNA in colonic inflammation. In inflammatory bowel disease (IBD), there is a high expression of pro-inflammatory cytokines and recent advances in the molecular pathogenesis of this disease have caused a shift towards novel biological approaches, including therapeutic gene silencing by RNAi, namely the use of siRNA against pro-inflammatory cytokines. However, gene silencing in IBD still needs improvement, therefore the co-delivery of siRNA with an antioxidant, as ascorbic acid, could significantly enhance therapeutic efficacy in the management of IBD. Also, the use of siRNA in colon diseases therapy is limited by its rapid clearance, high enzymatic degradation susceptibility of siRNA in biological media, high negative charge of the phosphate backbone and high molecular weight which contribute to its poor cellular uptake. The nanometric system proposed in this project has the ability to protect the encapsulated therapeutic agent, to prolong the time of action and to ensure its efficient intracellular delivery. The approach of formulating and developing the nanoparticles is by the quality by design concept, which is a promising tool to understand the sources of variability in a product formulation and to develop a product with improved characteristics following risk assessment techniques, therefore, it will ensure the development of an optimum formulation. Following formulation development, the nanometric system will be characterized in vitro, by evaluating gene silencing in cell cultures, and in vivo, by evaluating the activity of the system and gene silencing in murine induced colitis. Demonstrating that the developed delivery system allows increasing cell penetration and reduces inflammation by colonic gene silencing would have a significant impact on the progress of the development and applicability of RNA-based therapies.

Towards the enhancement of antitumor activity against cancer by co-delivery of combination chemotherapy in targeted drug delivery nanosystems Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-0781 2020 - 2022

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://combchemothernano.wpcomstaging.com/

Abstract:

Colorectal cancer (CRC) is deemed one of the leading causes of cancer-related deaths. Conventional chemotherapy for CRC involves a combination of multiple drugs, mainly containing 5-fluorouracil. Chemotherapy efficiency is often limited by a small sub-population of cells, named cancer stem cells (CSC) which show an increased tumorigenic potential, due to their ability to promote the progression of tumors. It is hypothesized that CSC are responsible for the formation of metastases and chemotherapy resistance. Therefore, a novel therapeutic approach, in order to enhance the efficacy of current chemotherapy, would be to specifically eliminate CSC. Salinomycin has recently been appraised as a potential anticancer drug selectively targeting CSC. Combination therapy is a cornerstone in cancer therapy. An ideal chemotherapy strategy would be to associate a cytotoxic drug which reduces the bulk of tumor to a drug that specifically eradicates CSC. However, most therapeutic approaches lack selectivity for tumor cells. Also, because the accessibility of the anticancer agents to tumor cells is limited, larger doses of cytotoxic drugs are needed, resulting in toxicity to healthy cells and increased risk of drug resistance. This highlights the need to find alternative ways of managing cancer, such as tumor-targeted drug delivery via nanocarriers. This project aims at developing PEGylated liposomes co-encapsulating a conventional cytotoxic drug such as 5-fluorouracil or gemcitabine together with salinomycin, as targeted drug delivery systems for CCR therapy. The advantage of co-delivery via nanocarriers is that they can deliver the two drugs in the same vesicle, thus allowing the possibility of synergism against the tumor cells, reducing the toxicity to normal cells, reversing drug resistance and enhancing the efficiency of chemotherapy.

Development of novel milk-based oral lyophilisates: focus on pediatric therapy Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-0795 2020 - 2022

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://lyokids.wordpress.com/home/

Abstract:

The objective of this study is to develop a new pharmaceutical form of pediatric use, oral lyophilisates having milk as a unique excipient. The implementation of the project will begin with a phase of bibliographic research and dosage form design, during which the behavior of milk as a freeze-dried matrix forming agent, thermal behavior during lyophilization and structure of lyophilized form will be studied. At the same stage, the quality profile of the oral lyophilisates and the critical quality characteristics, as well as the methods of evaluating them, will be established.

The study will continue with a phase in which, based on a design of experiments, the formulation and process factors that can influence the critical quality characteristics of oral lyophilisates will be optimized. Several types of milk will be studied and the results will be compared. At the end of this stage, the optimal factors will be identified that lead to a product with desired quality characteristics.

In the next stages, the oral lyophilisates will be loaded with different pharmaceutical substances, loratadine and ibuprofen and the effects of adding the substance on the properties of the finished product will be studied. A bioavailability study on rats will finally assess the in vivo performance of the new products.

: Increasing the competitiveness of AC HELCOR by implementing the QbD concept and process analytical technology, for the development of new medicinal products Call name: P 2 - SP 2.1 - Proiect de transfer la operatorul economic
PN-III-P2-2.1-PTE-2019-0445 2020 - 2022

Role in this project: Partner team leader

Coordinating institution: AC HELCOR SRL

Project partners: AC HELCOR SRL (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://www.achelcor.ro/increasing-competitiveness-ac-helcor-implementing-qbd-concept/

Abstract:

The objective of this project is to implement the concepts of quality by design (QbD) and process analytical technology (PAT) at AC HELCOR Pharmaceutical Company, in order to develop and place to the market a new pharmaceutical product. The application of these two modern concepts in the development of the new product will be possible through the collaboration between the academic environment, UMF Iuliu Hațieganu, and the pharmaceutical company AC HELCOR, by transfering in the economic environment the previous results and the expertise of the UMF group, with an impact on the competitiveness of the company on the pharmaceutical market at national and international level. According to the guidelines published by the regulatory agencies in the field of medicine (European Medicines Agency - EMA, Food and Drug Administration - FDA), the entire process of pharmaceutical development must be carried out based on scientific methods, combining risk assessment / management methods. , statistical experimental plans and methods enabling real-time monitoring of the manufacturing process. All these tools contribute to the development of robust products and processes, ensuring the reduction of failed manufacturing series and the constant production of a product that meets the established quality profile. This is made possible by identifying and controlling all input factors that exert an influence on the critical quality attributes of the product, respectively by real-time monitoring of these properties. The project involves the pharmaceutical development of a product of interest for the economic agent by applying these two concepts, the transposition on the technological manufacturing line followed by bioequivalence studies. The results obtained from these stages will represent a solid scientific support for the elaboration of the documentation necessary to authorize the marketing of the developed drug.

Implementation the Quality by Design concept in drug manufacture. Knowledge transfer UMF Cluj - Laropharm Call name: P 2 - SP 2.1 - Transfer de cunoaștere la agentul economic „Bridge Grant”
PN-III-P2-2.1-BG-2016-0201 2016 - 2018

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca (RO); LAROPHARM SRL (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca (RO)

Project website: https://qbdbridgeumfcjlph.wordpress.com/

Abstract:

The objective of the project is knowledge transfer concerning the Quality by Design (QbD) concept to the Laropharm company. Industrial practice showed that the raw materials present small variations in terms of their properties within the accepted pharmacopoeia requirements, and these small variations often lead to a poor quality of finished product, because the process is fixed and inflexible. Given in fact that the input variables (variations in the characteristics of raw materials) are not removable, the only way that the outcome remain fixed (the quality of pharmaceutical product) is to develop a robust process, very well known, in deep understood and flexible to input variables. Basically this means a new approach in drug production that means implementing Process Analytical Technology (PAT) in manufacturing and the development of the manufacturing process according to QbD concept. The project involves development the manufacturing process of a medicinal product of interest for the company, based on the two principles and to implement them on the company production line. Based on the obtained experimental data in both stage, technological and analytical development, but also during the technological transfer on production line the documentation required for the company to obtain the marketing authorization for the medicinal product will be done. The project responds to the current requirements of medical regulatory agencies from US and Europe (Administration Food and Drug Administration - FDA, European Medicines Agency - EMA) regarding to use the science and technology not only at new drugs discovery but also in their manufacturing in order to obtain high quality medicinal products.

Knowledge transfer to Vim Spectrum in the field of bioanalytical methods, pharmacokinetic analysis and biopharmaceutics Call name: P 2 - SP 2.1 - Transfer de cunoaștere la agentul economic „Bridge Grant”
PN-III-P2-2.1-BG-2016-0249 2016 - 2018

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca (RO); VIM SPECTRUM SRL (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca (RO)

Project website: https://113bg.wordpress.com/

Abstract:

The project aims knowledge transfer in the field of bioanalytical methods, pharmacokinetic analysis and biopharmacy from the Laboratory of Bioequivalence of UMF Iuliu Haţieganu Cluj-Napoca (LBUMF), with 18 years of activity, towards the Centre for Clinical and Analytical Research (CCCA) created in 2012 within Vim Spectrum pharmaceutical company from Târgu Mureș. Despite its 4 years of functioning and its modern and complete infrastructure, CCCA lacks the essential elements to achieve its objectives: lack of knowledge in the development and validation of bioanalytical methods for determination of drug substances in body fluids by analytical techniques like LC/MS, analysis of pharmacokinetics, biopharmacy and practical methodology to achieve bioequivalence studies and calculations with software for bioequivalence. These drawbacks got more acute in 2014, when the staff of the CCCA changed, the new staff members being unfamiliar with the mentioned issues, most of them being graduates of medicine, pharmacy and chemistry faculties. The transfer of knowledge from LBUMF to CCCA is based on: a) the broad and consistent experience of the research team from the LBUMF in bioanalytics, biopharmacy, pharmacokinetics and bioequivalence studies for drugs; b) the infrastructure, performance and quality of existing equipment at both partners which allows the methodologies developed with the infrastructure of LBUMF to be transferred and implemented at CCCA; c) together with training and knowledge transfer, a number of 9 bioanalytical methods will be developed and transferred to CCCA from the LBUMF, which is necessary for products under (re) authorization plan of Vim Spectrum. The theme of this project is consistent with the approved activities under the program BRIDGE Grant and legislation on scientific research and technological development or training human resources of high professionalism.

Quality by Design approach and development of Process Analytical Technology for a matrix type sustained–release product. Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-1862 2015 - 2017

Role in this project:

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca (RO)

Project website: https://qbdpatmatrixrs.wordpress.com/

Abstract:

The aim of the current proposal is to apply the Quality by Design (QbD) approach in development of the manufacturing technological process of matrix type sustained–release products and to use near infrared spectroscopy (NIRs) in association with chemometry as an adequate tool for Process Analytical Technology (PAT). The main factors affecting the release of drugs from hydrophilic matrix systems are related to drug characteristics (particle size, polymorphism), polymer (type, substituents of the side chain, particle size, intrinsic viscosity, percentage), formulation factors (other excipients, air trapped in the porosity, resistance to breakage) and technological factors (homogeneity of powder blend, compression force). Currently those factors are not monitored during the manufacturing process and variability affects product consistency (drug’s release profile/bioavailability) with consequences on quality of the final product. The project propose a scientific approach to overcome this difficulty by applying QbD order to define the Design Space in granulation, mixing and compression septs and development and validation NIRs methods for on-line monitoring of these steps. Therefore, the proposed project aims to find solutions for overcoming the problems of manufacturing high quality sustained release products by developing the innovative solution of applying enhanced process understanding via QbD in product development and NIRs as PAT tool for continuous process monitoring.

Development and preclinical evaluation of nanoparticulate drug delivery systems for targeted antitumor therapy of colorectal cancer Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-1060 2012 - 2016

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca (RO); UNIVERSITATEA BABES BOLYAI (RO); BIOTEHNOS SA (RO); UNIVERSITATEA DE STIINTE AGRICOLE SI MEDICINA VETERINARA CLUJ-NAPOCA (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE (U.M.F) Cluj-Napoca (RO)

Project website: https://pcca1060.wordpress.com/

Abstract:

The colorectal cancer remains a major health problem being the second cause of death by cancer in the world. Chemotherapy as major therapeutic approach for the treatment of cancer involves a high patient risk because of lack of tumor specificity of the cytotoxic drugs. Moreover the inefficiency and side effects of chemotherapy have been primarily associated with the formulation and biodistribution of the drug, toxicity to normal cells and the acquisition of drug resistance in the cancer cells. In order to overcome chemotherapy drawbacks, therapeutic bionanotechnologies based on the drug targeting concept might be a promise approach for cancer treatment.

Recent studies have shown the active involvement of inflammatory cells infiltrating the tumor, in tumor development by stimulating and supporting tumor angiogenesis. Tumor angiogenesis induced by the inflammatory pathways seems to be a central force in tumor growth and expansion. Inflammatory cell-targeting by using nanoparticulate delivery systems for certain drugs with primary or secondary anti-inflammatory effects in combination with nanoparticulate systems to deliver cytotoxic drugs to tumor cells might be a promise for the antitumor therapy.

Based on this approach, the aim of this proposal is to develop a successfull targeting strategy of two key cell players in tumor development, tumor and inflammatory cells. This aim will be accomplished by two main objectives: to develop suitable nanoparticulate drug delivery systems for selected drugs in the classes mentioned above and to assess their antitumor efficacy. The novelty of the proposal is to use a tumor targeting strategy for both processes vital for tumor progression, tumor cell proliferation and tumor-associated inflammation. Taking into account our premises, development of targeted antitumor nanosystems would have a significant impact on future anticancer therapy.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects