Customized photodynamic protocol with innovative porphyrins and redox modulators in premalignant cutaneous disorders - preclinical demonstration

PORPHYDERM

Project code: PN-III-P2-2.1-PED-2021-0360

Contract no: 637PED/2022

Programme: Proiect Experimental Demonstrativ (PED)

Domain: 1.3 - Biotehnology

Project duration: 28.06.2022 – 27.06.2024 (24 months)

Partner institutions

Proiectul este implementat de un consortiu multidisciplinar care are o lungă istorie de colaborare și expertiză în dezvoltarea preclinică de porfirine noi pentru PDT, precum și în medicina și terapia redox.

  • • Coordinator: Institutul Național de Cercetare - Dezvoltare în Domeniul Patologiei și Științelor Biomedicale „Victor Babeș”, project director: Dr. Gina MANDA
  • • Partner 1: Universitatea de Medicină și Farmacie “Carol Davila”, partner responsible: Prof. Rica BOSCENCU
  • • Partner 2: Biotehnos SA, partner responsible: Dr. Laura OLARIU

Budget

  • • From the national budget: 598.795 RON
  • • Own contribution: 53.895 RON
  • • Total value: 652.690 RON

ABSTRACT

The main objective is the development at preclinical level of a customized photodynamic therapy (PDT) protocol using smartly formulated porphyrinic photosensitizers and redox modulators for the treatment of premalignant cutaneous disorders such as actinic keratosis (AK). The project is in line with the call topic Bioeconomy - Biotehnology.

The medical application will be demonstrated in cells and mouse models by addressing both therapeutic efficacy and toxicological issues related to PDT on skin. We will start TLR 2 – technology/product concept formulated, with a portofolio of six patents and expertise in experimental PDT and in redox medicine. We will advance through TRL 3 – experimental proof of concept by performing in vitro and ex vivo studies using skin-relevant cells and animal skin explants. TRL 4 – technology/method validated in laboratory is expected to be reached by testing in animal models a customized procedure of keratolytic PDT in AK, using innovative photosensitizers and redox modulators. The activities will be organized in 5 work packages.

OBJECTIVES

Main objectives

The main objective is the development at preclinical level of a customized photodynamic therapy (PDT) protocol using smartly formulated porphyrinic photosensitizers and redox modulators for the treatment of premalignant cutaneous disorders such as actinic keratosis (AK). The project is in line with the call topic Bioeconomy - Biotehnology.

The medical application will be demonstrated in cells and mouse models by addressing both therapeutic efficacy and toxicological issues related to PDT on skin. We will start TLR 2 – technology/product concept formulated, with a portofolio of six patents and expertise in experimental PDT and in redox medicine. We will advance through TRL 3 – experimental proof of concept by performing in vitro and ex vivo studies using skin-relevant cells and animal skin explants. TRL 4 – technology/method validated in laboratory is expected to be reached by testing in animal models a customized procedure of keratolytic PDT in AK, using innovative photosensitizers and redox modulators. The activities will be organized in 5 work packages.

Secondary objectives

The main objective is the development at preclinical level of a customized photodynamic therapy (PDT) protocol using smartly formulated porphyrinic photosensitizers and redox modulators for the treatment of premalignant cutaneous disorders such as actinic keratosis (AK). The project is in line with the call topic Bioeconomy - Biotehnology.

The medical application will be demonstrated in cells and mouse models by addressing both therapeutic efficacy and toxicological issues related to PDT on skin. We will start TLR 2 – technology/product concept formulated, with a portofolio of six patents and expertise in experimental PDT and in redox medicine. We will advance through TRL 3 – experimental proof of concept by performing in vitro and ex vivo studies using skin-relevant cells and animal skin explants. TRL 4 – technology/method validated in laboratory is expected to be reached by testing in animal models a customized procedure of keratolytic PDT in AK, using innovative photosensitizers and redox modulators. The activities will be organized in 5 work packages.

STUDY DESIGN

PROJECTED RESULTS

1) At least 2 new porphyrinic compounds with improved properties as compared to commercial photosensitizers for the treatment of actinic keratosis (AK). Improvements are expected in terms of amphiphilicity, fluorescence for in vivo imaging, significant singlet oxygen yield for PDT and good stability / preservation of photodynamic properties in the topical formulation.

2) Technical specifications for all formulated porphyrinic compounds and phytochemicals, as well as for the selected PDT protocol and its outcome in AK mice.

3) Documentation for at least 3 patent requests, submitted to the Romanian Patent and Trademark Office.

4) Two porphyrinic compounds registered at the European Chemicals Agency.

5) At least 2 publications in journals with impact factor > 4, and at least 2 communications at relevant congresses in the field of dermatology, toxicology and redox biology (we take into consideration that patent-associated results should not be previously published).

6) A workshop organized at the end of the project for presenting results to stakeholders (academia, dermatologists and pharmaceutical SMEs).

7) New research services on preclinical testing of new PDT strategies in dermatology, to be implemented at: IVB (PDT on tumor cells and small laboratory animals), and at BTH (in vitro PDT on skin-relevant cells, technological process for formulation of porhyrins and redox-modulating phytochamicals), to be published in eERIS.

8) Detailed development and market strategy, taking also advantage of the COST Action CA20121 which creates the collaboration frame with pharmaceutical SMEs in redox medicine and pharmaceutics.

9) Dedicated web page and social media channels for promoting the knowledge generated in the project towards specialists, pharmaceutical industry and the general public.

SUMMARY OF STAGE I /2022

Synthesis and preliminary characterization of new porphyrin compounds

Recent statistics highlight cancer as the leading cause of death worldwide, predicting an increase in the number of cases compared to 2020 by 47% by 2040 [1,2]. For these reasons, the development of innovative strategies regarding the dissemination of preventive measures and the supply of active substances with antitumor potential are essential for fighting cancer worldwide. Non-melanoma lesions (actinic keratoses, squamous and basal cell carcinoma, cutaneous lymphoma, Kaposi's sarcoma, angiosarcoma) are among the most common forms of cancer. The development of a non-melanoma cancer is determined by genetic factors, history of HPV infection, history of chronic inflammatory skin conditions, exposure to toxic substances, sun, immunosuppression, skin phototypes I and II, PUVA as previous therapy [3, 4]. Actinic keratoses are described in the literature as "carcinoma in situ" (due to dysplastic keratinocytes similar to squamous cell carcinoma) or as a premalignant lesion [5]. The therapeutic approach in the case of actinic keratosis must aim at reducing the risk of malignancy and an early diagnosis of malignant formations that may appear in a field of actinic keratosis. Porphyrins, through their structural and spectral profile, have potential in the identification and therapy of malignant skin manifestations [6]. In addition, the major advantage of these heme-like structural types is the selectivity for tumor cells and their versatility, the possibility of structural modeling by attaching substituents with different degrees of polarity, to obtain an optimal hydrophilic/lipophilic ratio for cellular internalization.

In this context, the main objective of the project is to develop a protocol for photodynamic therapy (PDT) of actinic keratosis, using new porphyrinic derivatives. The activities within the project include the evaluation of the marker and antitumor agent potential of some porphyrinic compounds with asymmetric molecular architecture and appropriate spectral profile. A first stage of the project envisages obtaining new porphyrinic structures, through ecological synthesis techniques that respected the current requirements in the field of drug synthesis. It was aimed to obtain a set of data associated with the synthesis procedures and the parameters that define the structural profile of the new photosensitizers.

As part of Activity I.1 carried out by UMF, the following porphyrinic compounds were obtained:

  • • with asymmetric structures:
  •  5-(2,4-dihydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (P4.2)
  •  5-(2-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl)porphyrin (P 5.2)
  • • with symmetric structures (reference for asymmetric derivatives in in vitro studies)
  •  5,10,15,20-meso-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P4.1 P2.1)
  •  5, 10,15,20-tris-(4-carboxymethylphenyl) porphyrin (P 5.1)

The structural and spectral evaluation of the synthesized compounds was carried out in Activity I.1 by NMR, FTIR, UV-Vis and fluorescence analysis. Correlation of the obtained data confirmed the structures of the porphyrinic compounds synthesized at this stage. In conclusion, the preliminary studies led to obtaining, with good yields, 4 porphyrinic compounds by approaching a modern and ecological synthesis method.

In Activity I.2, 3 types of formulations for topical applications of porphyrinic compounds and modulators were analyzed, in the first stage the gel method was selected and detailed.

The in vitro study carried out in Activity I.3 showed that all porphyrinic compounds analyzed, evaluated in vitro on normal and tumor-specific skin cells (normal human keratinocytes HaCaT, human dermal fibroblasts HS27 and mouse melanoma cells B16F10) had good biocompatibility with normal and tumor skin cells. However, the following aspects are worth noting: 1) compound P5.2 can inhibit the multiplication of keratinocytes, which has therapeutic relevance in the case of actinic keratosis characterized by the hyper-proliferation of these cells, if temporary photosensitization of the skin is avoided; b) compounds P2.1 and P5.2, but not the porphyrinic derivative P4.2, increase LDH release by dermal fibroblasts, possibly due to undesirable effects that disrupt the membrane integrity of dermal fibroblasts.

All analyzed porphyrinic compounds incorporated into normal and tumor skin cells investigated, it is true with different intensities, thus proving fluorescent marker properties. The porphyrinic compounds P2.1 and P4.2 can be considered as candidates for fluorescence imaging in dermatology, and for PDT in dermatology oncology.

For the visibility of the project and its achievements, in Activity I.4 the web page of the project was created, which can be found at

https://www.ivb.ro/porphyderm

In Activity I.5, coordinated by UMF, the patent application with the title "Porphyrinic compound with fluorescent marker potential in dermato-oncology" was developed, in which all partners participated. The technical documentation of the patent application claims novel elements corresponding to the obtaining, spectral and biological evaluation of the compound 5-(2-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl) porphyrin (P5.2) . The patent application was registered at OSIM.

The objective and activities of phase I were 100% achieved.

SUMMARY OF STAGE II /2023

Intermediate preclinical study

STAGE II ACTIVITIES

Activity

Partener

Activitatea II.1

Synthesis and characterization of some porphyrinic compounds for preclinical studies

UMF (P1)

Activitatea II.2

Obtaining, formulating and characterizing some phytocompounds

BTH (P2)

Activitatea II.3

In vitro biological study

IVB (CO)

Activitatea II.4

Formulation of porphyrinic compounds and redox modulators for topical application

BTH (P2)

Activitatea II.5

Ex vivo biological study on skin explants

BTH (P2)

Activitatea II.6

Preliminary in vivo study in animal model

IVB (CO)

Activitatea II.7

Studiu preliminar in vivo in model animal

IVB (CO)

Activitatea II.8

Evaluation of skin homeostasis in an animal model of actinic keratosis with various treatments

BTH (P2)

Activitatea II.9

Dissemination of results: web page update, articles, communications, international partnership

IVB (CO)

UMF (P1)

 

 

 

STAGE II RESULTS

Projected results

Achieved results

2 selected porphyrin compounds

intermediate technical specifications

3 porphyrinic compounds with technical specifications: P2.1, P2.2 and P4.2

2 phytocompounds with their technical specifications

2 phytocompounds with technical specifications

1 final in vitro biological study report

Preliminary in vitro study report. The results are presented in the article sent for publication in an ISI journal.

1 interim study report on skin explants

The method of obtaining and testing skin explants for vertical diffusion studies of topical and transdermal preparations;

• HPLC method for porphyrinic compounds; 

• Protocol for performing PDT on skin explants.

2 porphyrinic compounds and 2 phytocompounds formulated for topical application

Variants of gels for the topical formulation of photosensitizers and phytocompounds for PDT on the skin.

1 ex vivo PDT protocol on skin explants

Ex vivo PDT protocol on skin explants

2 animal models of actinic keratosis

2 characterized animal models (repeated exposure to UVB, transplantable tumors of human skin carcinoma cells with squamous cells in immunosuppressed nude mice);

A third model is in progress (chemically induced carcinogenesis in FAV mice).

1 preliminary in vivo study report

Preliminary in vivo study report on C57BL/6 mice repeatedly exposed to increasing doses of UVB and treated in vivo with phytocompounds.

NRF2 target genes panel

Panel of target genes of NRF2, relevant for photodynamic therapy

1 protocol of combined PDT therapy and redox modulation in a preclinical model

1 protocol of combined PDT therapy and redox modulation in preclinical model

1 in vivo skin investigation procedure

In vivo skin investigation procedure

Updated web page

PORPHYDERM – National Institute of Pathology Victor Babeş – Bucharest (ivb.ro)

2 scientific communications

 

• 1 scientific communication at the Autumn Scientific Conference of AOSR 2023 with the title "Science for a healthy society", organized between 21-23.09.2023 OVIDIUS University of Constanța;

• 1 oral presentation in the field of the transcription factor NRF2 in cancer at the "NRF2 in Noncommunicable Diseases: from Bench to Bedside" Course, organized within the COST Action CA20121 between 26-30.06.2023 at Smolenice Castle, Slovakia.

2 published scientific articles

• 1 article published in 2023 in Molecules magazine (ISI, impact factor 2023 4.927);

1 article submitted for publication in Pharmaceuticals magazine (ISI, impact factor 5.215).

• 3 patent requests submitted at OSIM and 1 national patent granted

• 1 patent application was submitted to OSIM with no. of registration A/00775/28.11.2022 and with the title "Porphyrin compound with fluorescent marker potential in dermato-oncology" (submission reported in advance in stage I);

• For one of the compounds tested during this stage, patent No. 132752 B1 was granted, published in RO-BOPI, 11 of 29.11.2023, with the title "Porphyrin derivative for theranostic use", authors: Rica Boscencu, Gina Manda, Radu Petre Socoteanu, Mihail Eugen Hinescu, Ionela Victoria Neagoe, Laura Olariu, Brandusa Dumitriu.

1 patent application in progress

1 patent application is being developed regarding the formulation of the photosensitizers selected in stages 1 and 2 of the project for topical application in PDT.

2 collaboration protocols with experts from abroad

3 collaboration protocols with experts from abroad

 

 

SUMMARY OF STAGE III/2024

Preclinical validation study

STAGE III ACTIVITIES

Activity

Partener

Activity III.1

Synthesis and characterization of porphyrinic compounds selected for the validation study

 

UMF (P1)

Activity III.2

Obtaining, formulation and characterization of the porphyrinic compound and the phytocompound selected for validation

 

BTH (P2)

UMF (P1)

Activitatea III.3

Biologic ex vivo study on the combined photodynamic therapy and redox modulation on skin explants from mice with actinic keratosis

 

BTH (P2)

IVB (CO)

Activitatea III.4

Biologic in vivo validation study of the combined photodynamic therapy and redox modulation in mice with actinic keratosis

 

IVB (CO)

Activitatea III.5

Dissemination of results

IVB (CO)

UMF (P1)

Activitatea III.5.1

Website update, technologic transfer protocol, demonstrative workshop

 

IVB (CO)

Activitatea III.5.2

Final documentation of the preclinical validation study and its dissemination

 

UMF (P1)

 

 

 

STAGE 3 RESULTS

Projected results

Achieved results

1 compus porfirinic validat

si specificatia sa tehnica finala

• Porphyrinic compound P2.2 validate in vitro and in animal model of chemically-induced carcinomatosis

Porphyrinic compounds P2.1 and P4.2 validated in vitro

Technical specifications of the compounds P2.1, P2.2 and P4.2;

1 compus porfirinic formulat

• 2 porphyrinic compounds (P2.1 and P2.2) formulated in gels for topical applications (chitosan and hydroxypropyl methylcellulose );

2 patent documentations of gels with porphyrin

1 fitocompus formulat si specificatia sa tehnica

• 1 formulated phytocompound and its technical specification

1 raport de studiu de validare ex vivo

• 1 report on the in vivo study in animal model of mice chronically exposed to UVB

• Database with skin parameters evaluated by non-invasive methods in mice chronically exposed to UVB and treated by PDT and/or with redox modulators;

1 protocol de investigare ex vivo a pielii

• Protocol of ex vivo skin investigations

1 studiu biologic de validare in vivo

• In vivo validation of the P2.2 porphyrinic compound in an animal model of chemically-induced carcinogenesis and in an animal model of chronic exposure to UVB

1 portofoliu de metode experimentale

• Synthesis and characterization of porphyrinic compounds

o Physico-chemical and pharmaco-technic characterization of gels with porphyrins

o Photodynamic therapy in vitro and in vivo in mouse models

·       PDT in vitro si in vivo

o Non-invasive in vivo characterization of mice skin

1 pagina web actualizata

PORPHYDERM – National Institute of Pathology Victor Babeş – Bucharest (ivb.ro)

1 protocol de transfer tehnologic intre parteneri

• Know-how transfer from IVB (CO) to BTH (P2) regarding the in vitro investigation of photosensitizers for photodynamic therapy

1 cerere de brevet depusa la OSIM

• 3 patent requests submitted at OSIM and 1 national patent granted

·      Cerere de brevet A00567 din 23.09.2024 Porfirină asimetrică în matrice de hidroxipropilmetilceluloză pentru tratamentul afecțiunilor cutanate premaligne. Autori: Emma Adriana Ozon, Andreea Mihaela Burloiu, Rica Boscencu, Gina Manda, Valentina Anuta, Cristina Elena Dinu Pirvu, Dumitru Lupuliasa, Neagoe Ionela Victoria, Adina Magdalena Musuc, Mihai Anastasescu, Radu Petre Socoteanu.

·      Cerere de brevet A00630 din 23.10.2024 Hidrogel cu porfirina in asociere cu chitosan pentru potentiale aplicatii in dermato-oncologie. Autori: Olariu Laura, Boscencu Rica, Manda Gina, Serbu Sabina, Burloiu Andreea-Mihaela, Mihai Dragoș-Paul, Ene Manuela Diana.

Brevet obtinut

Derivat porfirinic pentru utilizare în teranostică. Autori:  Rica Boscencu, Gina Manda, Radu Socoteanu Mihail Eugen Hinescu, Ionela Victoria Neagoe Laura Olariu, Brandusa Dumitriu. RO132752 (A0) 2018-08-30, RO132752 (B1) 2023-11-29.

2 compusi porfirinici inregistrati la European Agency of Chemicals

Este in curs de pregatire documentatia de inscriere a 2 compusi porfirinici (P2.1 si P2.2), pentru care insa trebuie realizat un studiu toxicologic mai amplu, neprevazut in proiect.

Acest livrabil, care nu a fost definitivat in proiect, este compensat de 2 publicatii ISI suplimentare.

1 workshop demonstrativ

• Demonstrative workshop organized by IVB (CO) on 8.10.2024

o PORPHYDERM at a glance (Gina Manda, IVB)

o In silico analysis of porphyrinic compounds (Dragos Mihai, UMF)

o Innovative porphyrinic compounds for photodynamic therapy in non-malignat skin pathology (Rica Boscencu, UMF)

o Patent on the porphyrinic compound P4.2 –Gold medal at E U R O I N V E N T 2024 (Laura Olariu, BTH)

o Innovative porphyrinic compounds for photodynamic therapy in non-malignat skin pathology (Rica Boscencu, UMF)

o Discussion and future plans.

Rezultate suplimentare

• 3 published articles

1. Assessment of some unsymmetrical porphyrins as promising molecules for photodynamic therapy of cutaneous disorders. Burloiu, A.M., Manda, G., Lupuliasa, D., Socoteanu, R.P., Mihai, D.P., Neagoe, I.V., Anghelache, L.I., Surcel, M., Anastasescu, M., Olariu, L., Gîrd, C.E., Barbuceanu, S.F., Ferreira, L.F.V., Boscencu, R. Pharmaceuticals, 17(1), 62, 2024 (F.I.=4.3, Q1). This research was supported by the Romanian Ministry of Research, Innovation and Digitalization through the grant 637PED/2022 and the Nucleu grant PN 23.16.02.01/2023.

2. In silico and in vitro studies on an asymmetrical porphyrin derivative with therapeutic potential in skin disorders. Burloiu, A.M., Mihai, D.P., Manda, G., Lupuliasa, D., Neagoe, I.V., Socoteanu, R.P., Surcel, M., Anghelache, L.I., Olariu, L., Gîrd, C.E., Boscencu, R. Pharmaceuticals, 17(6), 688, 2024 (F.I.=4.3, Q1). This research was supported by the Romanian Ministry of Research, Innovation and Digitalization through the grant 637PED/2022, the Nucleu grant PN 23.16.02.01/2023, and by “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania.

3.  Porphyrin photosensitizers into polysaccharide-based biopolymer hydrogels for topical Photodynamic Therapy: Physicochemical and pharmacotechnical assessments. Burloiu, A.M., Ozon, E.A., Musuc A.M., Anastasescu M., Socoteanu R.P., Atkinson, I., Culita D., Anuta, V., Popescu, I.A., Lupuliasa, D., Mihai, D.P., Gîrd, C.E., Boscencu, R. Gels, 2024, 10, 499. (F.I.=5, Q1). This research was supported by the Romanian Ministry of Research, Innovation and Digitization.

2 lucrari comunicate:

·      16th European Exhibition of Creativity and Innovation Iasi, Romania, 6-8 June 2024: Porphyrynic Derivative for Theranostics Use Patent No. 132752 B1 published in RO-BOPI, 11 from 29 November 2023, Laura Olariu, Rica Boscencu, Gina Manda, Radu Socoteanu, Mihail Eugen Hinescu, Ionela Victoria Neagoe, Brandusa Dumitriu. Comunicare poster care a primit Medalie de aur.

·      23rd Romanian International Conference on Chemistry and Chemical Engineering (RICCCE), Mamaia – Constanța, Romania, 4-7 September, 2024: Morphological and spectral assessment of an unsymmetrical porphyrinic complex with biomedical potential, Elena Christen Creanga, Rica Boscencu, Roxana Trusca, Adina Magdalena Musuc, Radu Socoteanu, Mihai Anastasescu.

 

 

Diseminare in proiectul PORPHYDERM

• Website: PORPHYDERM – National Institute of Pathology Victor Babeş – Bucharest (ivb.ro)
• 3 national patent requests submitted at OSIM:

  • 3 cereri de brevet depuse la OSIM:
  1. Porphyrinic compound with potential as fluorescent marker in dermato-oncology. Burloiu Andreea Mihaela, Manda Gina, Boscencu Rica, Neagoe Ionela Victoria, Lupuliasa Dumitru, Surcel Mihaela, Olariu Laura, Mihai Dragos Paul. Patent 202200775, published in RO-BOPI 5/30.05.2023.
  2. Assymetric porphyrin in hydroxypropyl methylcellulose for the treatment of premalignant skin pathology. Emma Adriana Ozon, Andreea Mihaela Burloiu, Rica Boscencu, Gina Manda, Valentina Anuta, Cristina Elena Dinu Pirvu, Dumitru Lupuliasa, Neagoe Ionela Victoria, Adina Magdalena Musuc, Mihai Anastasescu, Radu Petre Socoteanu. Patent request A00567 from 23.09.2024.
  3. Hydrogel with porphyrin in association with chitosan for dermato-oncology applications. Olariu Laura, Boscencu Rica, Manda Gina, Serbu Sabina, Burloiu Andreea-Mihaela, Mihai Dragoș-Paul, Ene Manuela Diana. Patent request A00630 from 23.10.2024.
  • • 4 articles published in ISI journals, 3 in Q1 and 1 in Q2:
    1. Porphyrin macrocycles: general properties and theranostic potential. Boscencu, R., Radulea, N., Manda, G., Machado, I.F., Socoteanu, R.P., Lupuliasa, D., Burloiu, A.M., Mihai, D.P., Ferreira, L.F.V. Molecules, 28(3), 11492023, 2023 (F.I.=4.2, Q2). The research was supported by the Ministry of Research, Innovation and Digitalization, Romania, through PORPHYDERM project (ctr. no. 637PED/2022) and the Nucleu project PN 23.16.02.01/2022.
    2. 2. Assessment of some unsymmetrical porphyrins as promising molecules for photodynamic therapy of cutaneous disorders. Burloiu, A.M., Manda, G., Lupuliasa, D., Socoteanu, R.P., Mihai, D.P., Neagoe, I.V., Anghelache, L.I., Surcel, M., Anastasescu, M., Olariu, L., Gîrd, C.E., Barbuceanu, S.F., Ferreira, L.F.V., Boscencu, R. Pharmaceuticals, 17(1), 62, 2024 (F.I.=4.3, Q1). This research was supported by the Romanian Ministry of Research, Innovation and Digitalization through the grant 637PED/2022 and the Nucleu grant PN 23.16.02.01/2023.
    3. In silico and in vitro studies on an asymmetrical porphyrin derivative with therapeutic potential in skin disorders. Burloiu, A.M., Mihai, D.P., Manda, G., Lupuliasa, D., Neagoe, I.V., Socoteanu, R.P., Surcel, M., Anghelache, L.I., Olariu, L., Gîrd, C.E., Boscencu, R. Pharmaceuticals, 17(6), 688, 2024 (F.I.=4.3, Q1). This research was supported by the Romanian Ministry of Research, Innovation and Digitalization through the grant 637PED/2022, the Nucleu grant PN 23.16.02.01/2023, and by “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania.
    4. Porphyrin photosensitizers into polysaccharide-based biopolymer hydrogels for topical Photodynamic Therapy: Physicochemical and pharmacotechnical assessments. Burloiu, A.M., Ozon, E.A., Musuc A.M., Anastasescu M., Socoteanu R.P., Atkinson, I., Culita D., Anuta, V., Popescu, I.A., Lupuliasa, D., Mihai, D.P., Gîrd, C.E., Boscencu, R. Gels, 2024, 10, 499. (F.I.=5, Q1). This research was supported by the Romanian Ministry of Research, Innovation and Digitization.

 

  • • Communications

Oral presentations

Autumn Scientific Conference of AOSR 2023 ”science for a healthy society”, organized on la 21-23.09.2023 at OVIDIUS University Constanța, Romania;

COST CA20121 „NRF2 in Noncommunicable Diseases: from Bench to Bedside”, 26-30 June 2023, Smolenice Castle, Slovacia, NRF2 in cancer and radiotherapy, Gina Manda.

 

Poster presentations

  1. 16th European Exhibition of Creativity and Innovation Iasi, Romania, 6-8 June 2024. Porphyrynic Derivative for Theranostics Use Patent No. 132752 B1 published in RO-BOPI, 11 from 29 November 2023, Laura Olariu, Rica Boscencu, Gina Manda, Radu Socoteanu, Mihail Eugen Hinescu, Ionela Victoria Neagoe, Brandusa Dumitriu. Medalie de aur
  2. 23rdRomanian International Conference on Chemistry and Chemical Engineering (RICCCE), Mamaia – Constanța, Romania, 4-7 septembrie 2024. Morphological and spectral assessment of an unsymmetrical porphyrinic complex with biomedical potential, Elena Christen Creanga, Rica, Boscencu, Roxana Trusca, Adina Magdalena Musuc, Radu Socoteanu, Mihai Anastasescu.

 

  • 3 collaboration letters

Prof. Antonio Cuadrado, Faculty of Medicine, University Autonoma of Madrid & Institute of Biomedical Research, Ciudad Universitaria de Cantoblanco, 28049 Madrid, Spain & C. de Arturo Duperier, 4, 28029 Madrid, Spain, email: antonio.cuadrado@uam.es.

Devrim Pesen Okvur, Izmir Institute of Technology, Gülbahçe, İzmir Yüksek Teknoloji Enstitüsü, 35433 Urla/İzmir, Turkey, email: devrimpesen@iyte.edu.tr in vitro a terapiei fotodinamice.

Prof. Prof. Luís Filipe Vieira Ferreira, Universidade de Lisboa, Centro de Química-Física Molecular, Complexo Interdisciplinar, Instituto Superior Técnico, Av. Rovisco Pais 1049-001, Lisboa, Portugal Email: LuisFilipeVF@ist.utl.pt, Tel: 351-21 84 19 252 / 246 / 039.

  • • European networks

COST Action CA20121 „Bench to Bedside transition for Pharmacological regulation of NRF2 in noncommunicable diseases”, acronim BenBedPhar, 2021-2025, Chair: Prof. Antonio Cuadrado, Autonomous University of Madrid, Spania, Vice-chair: Gina Manda (PED coordinator), Grant Holder: INCD ”Victor Babeș”, Romania

  • • Defended PhD theses
  1. Metalic nanosystems functionalized for theranostic in cancer, 2023. PhD student Laurențiu-Iliuță Anghelache, PhD coordinator Prof. Univ. Dr. Maria Crivineanu (USAMVB);
  2. Interdisciplinary studies on some tetrapyrrholyc with potential application in oncologic dermatology, 2024. PhD student: Andreea Mihaela Burloiu, PhD coordinator: Prof. Dr. Dumitru Lupuliasa (UMF „Carol Davila”).
  • • PhD students

Serbu Sabina (P2): studies for obtaining and characterizing hydrogels with application in the pathology of epithelial tissues – Scientific coordinator: Prof. Dr. Rica Boscencu (P1).

 

 

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