Dynamic platforms based on oligo/polysaccharides networks obtained through thiol-ene coupling for biomedical applications (THIOLENET)

The THIOLENET project objective is the development, preparation, and optimization of innovative biomaterials based on chitosan and cyclodextrin through radical addition thiol-ene covalent crosslinking reaction.

Project concept and specific objectives:

WP1. Synthesis, and characterization of precursors for thiol-ene coupling reactions

A1.1. Synthesis and characterization of chitosan modified with alkene moieties;

A1.2. Synthesis and characterization of chitosan modified with thiol moieties;

A1.3. Synthesis and characterization of cyclodextrins modified with alkene moieties;

A1.4. Synthesis and characterization of cyclodextrins modified with thiol moieties.

WP2. Preparation and characterization of hydrogels and submicron particles through thiol-ene covalent crosslinking reaction

A2.1. Development of methods for hydrogel preparation using the already selected precursors;

A2.2. Development of methods for submicron particle preparation using the already selected precursors;

A2.3. Influence of crosslinking reaction parameters on the physicochemical properties of the obtained hydrogels/particles studies

WP3. Demonstration of applicative potential of the new biomaterials

A3.1. Toxicity studies

A3.2. Drug encapsulation and release in relation to variable crosslinking reaction parameters studies

THIOLENET novel features are:

Synthesis of chitosan/cyclodextrin materials with improved drug absorption/delivery kinetics; the thiol-ene coupling between chitosan and cyclodextrin derivatives with a controlled amount of functionalities available for the thiol-ene reaction will be used for the first time. In addition, a systematic study of the structural factors that are influencing covalent crosslinking will be performed.

Estimated results:

New research directions will be issued by modifying the crosslinking reaction parameters: new biomaterials will be developed starting with chemically modified components having modulable drug release kinetics while maintaining low toxicity and adjustable properties in terms of size (for particles), rheological properties (for hydrogels), pores size (for hydrogels and particles), hydrophilicity/hydrophobicity. The current project will provide the tools for further development in this particular scientific area. At the fundamental level, the approach of synthesis of chitosan network crosslinked with cyclodextrins by thiol-ene reaction represents a new and valuable concept for this class of compounds, thus expanding the applicability of thiol-ene coupling. In addition, by studying the influence of reaction parameters on the final physical-chemical properties of the hydrogel/particle, important fundamental information will be achieved which in turn will allow further expansion of the scientific field. The envisaged systematic studies will allow better control over the preparation methods thus enabling their possible application in the pharmaceutical industry.

Project Dissemination:

• 5 articles published in ISI-ranked journals;
• 1 patent application;
• 2 presentations at international conferences/per year;
• 3 scientific reports.

Details regarding the exploitation and dissemination of results at the project level (2022-2024)

Achieved indicators:

• Publication of 6 ISI papers (Q1/Q2) - 100% Achieved;
• Participation with scientific papers at 12 international conferences - 100% Achieved
• 1 patent application - 100% Achieved
• Writing of annual research reports and final research report - 100% Achieved
• Project website - 100% Achieved

Published ISI articles

1. Logigan, C.-L.; Delaite, C.; Tiron, C.-E.; Peptu, C.; Popa, M.; Peptu, C.A. Chitosan Grafted Poly (Ethylene Glycol) Methyl Ether Acrylate Particulate Hydrogels for Drug Delivery Applications. Gels 2022, 8, 494, Impact factor: 5,0
2. Cristian Peptu, Diana-Andreea Blaj, Mihaela Balan-Porcarasu, Catalina A. Peptu, Valeria Harabagiu. Custom-modified oligolactide-cyclodextrin derivatives for electrospun drug formulations. European Polymer Journal, Volume 196, 2023, 112234, Impact factor: 3.862
3. Diaconu A-D, Logigan C-L, Peptu CA, Ibanescu C, Harabagiu V, Peptu C. Polyurethane Degradable Hydrogels Based on Cyclodextrin-Oligocaprolactone Derivatives. Gels. 2023; 9(9):755, Impact factor: 4,6
4. Corina-Lenuța Logigan, Christelle Delaite, Marcel Popa, Elena Simona Bacaita, Crina Elena Tiron, Cristian Peptu and Catalina Anișoara Peptu. Poly(ethylene glycol) methyl ether acrylate grafted chitosan based micro and nanoparticles as a drug delivery system for antibiotics. Polymers, Impact factor: 5,0
5. T Bibire, R DANILA, Corina-Lenuța Logigan, Catalina Anisoara PEPTU, RS Cozma, Cristina Mihaela Ghiciuc. Chitosan-gelatin micro/nanoparticles as a controlled delivery of dexketoprofen trometamol for topical applications in wound care.i Med. Surg. J. –Rev. Med. Chir. Soc. Med. Nat., Iaşi2024, 128(2):411-421, doi: 10.22551/MSJ.2024.02.21, Impact factor: 1,044
6. Blaj DA, Peptu CA, Danu M, Harabagiu V, Peptu C, Bujor A, Ochiuz L, Tuchiluș CG. Enrofloxacin Pharmaceutical Formulations through the Polymer-Free Electrospinning of β-Cyclodextrin-oligolactide Derivatives. Pharmaceutics. 2024 Jul 5;16(7):903. doi: 10.3390/pharmaceutics16070903. PMID: 39065598; PMCID: PMC11279624, Impact factor: 5,4

ISI articles in progress

1. Corina-Lenuta Logigan, Cristian Peptu, Mihaela Balan-Porcarasu, Maricel Danu, Catalina-Anisoara Peptu. Development of Novel Gels Based on Cyclodextrin Functionalized with Double Bonds and Thiolated Chitosan via Thiol-Ene Coupling
2. Corina-Lenuta Logigan, Cristian Peptu, Catalina-Anisoara Peptu. Innovative Nanoparticulate Polymer Supports via Thiol–Ene Polymer Conjugation for Enhanced Drug Delivery

Published book chapter

2. Corina L. Logigan, Cristian Peptu, Catalina A. Peptu. Chapter 17 - Liposomes for delivery of substances for other (non-therapeutic) applications, Editor(s): Sophia G. Antimisiaris, Liposomes in Drug Delivery, Academic Press, 2024, Pages 435-460, ISBN 9780443154911, https://doi.org/10.1016/B978-0-443-15491-1.00014-6.

Patent application submitted to OSIM

2. Patent application no. A00651 /30.10.2024 with title ,,Preparation process of micro/nanoparticles from cyclodextrin and chitosan derivatives by photoinduced nanoprecipitation ”

Participation at international conferences

1. NanoMedicine International Conference - NanoMed 2022
Chitosan grafted poly (ethylene glycol) methyl ether acrylate based micro/nanocarriers for biomedical applications.
Authors: Peptu, C.A.; Logigan, C.-L.; Delaite, C.; Tiron, C.-E.; Peptu, C.; Popa, M.
2. NanoMedicine International Conference - NanoMed 2022
Nanoparticles based on chitosan grafted with PEG derivative as carriers for antibiotics.
Authors: Logigan, C.-L.; Peptu, C.A.; Delaite, C.; Tiron, C.-E.; Peptu, C.; Popa, M.
3. 6th International Conference on Chemical Engineering – ICCE 2022
Cyto- and hemocompatible nanoparticles based chitosan grafted poly (ethylene glycol) methyl ether acrylate as a novel drug delivery system.
Authors: Logigan, C.-L.; Peptu, C.A.; Delaite, C.; Tiron, C.-E.; Peptu, C.; Popa, M.
4. Congresul Internațional al Universității „Apollonia” din Iași, Pregătim viitorul promovând excelența, Ediția a XXXIII-a , 2 - 5 Martie, IAȘI, ROMANIA
Chitosan Grafted Poly (Ethylene Glycol) Methyl Ether Acrylate Nanoparticles: Synthesis, Characterization, and Use as Drug Delivery System.
Authors: Peptu, C.A.; Logigan, C.-L.; Delaite, C.; Tiron, C.-E.; Peptu, C.; Popa, M.
5. Progress in Organic and Macromolecular Compounds, 29th Edition, Iasi, Romania, October 4 - 6
Design and synthesis of particles based on chitosan grafted poly(ethyleneglycol) methylether acrylate as carriers for antibiotics.
Authors:Peptu, C.A; Logigan, C.-L.; Delaite, C.; Tiron, C.-E.; Peptu, C.; Popa, M.
6. 2nd International Conference on Advanced Nanomaterials and Nanotechnology, 20-21 November, Viena, Austria
Chitosan grafted poly(ethylene glycol) methyl ether acrylate nanoparticles as drug delivery system.
Authors: : Peptu, C.A.; Logigan, C.-L.; Delaite, C.; Tiron, C.-E.; Peptu, C.; Popa, M.
7. 2nd International Conference on Advanced Nanomaterials and Nanotechnology, 20-21 November, Viena, Austria
Design of innovative gels based on thiolated chitosan and double bonds functionalized cyclodextrin formed via thiol-ene coupling.
Authors: Logigan, C.-L.; Peptu, C.; Peptu, C.A
8. Congresul Internațional al Universității „Apollonia” din Iași, Pregătim viitorul promovând excelența, Ediția a XXXIV-a , 29 februarie - 3 martie 2024, IAȘI, ROMANIA.
Synthesis and Characterization of New Films Comprising Cyclodextrin Functionalized with Double Bonds and Thiolated Chitosan Through Thiol-Ene Coupling.
Authors: Logigan, C.-L.; Peptu, C.; Peptu, C.A.
9. 40th Informal Meeeting on Mass Spectrometry 2024.
MALDI MS quantification of transesterification reactions in the ring-opening polymerization of lactides.
Authors: Blaj D., Peptu, C.
10. 26th International Conference, 15-18 August 2024, Burgas, Bulgaria.
Gels Derived from Chitosan and Cyclodextrin via Thiol-Ene Coupling.
Authors: Peptu, C.A.
11. Nanomed International Conference and Exhibition, 23-25 October 2024 Barcelona, Spania.
Innovative Nanoparticulate Polymer Supports via Thiol–Ene Polymer Conjugation for En-hanced Drug Delivery.
Authors: Logigan, C.-L.; Peptu, C.; Peptu, C.A.
12. Nanomed International Conference and Exhibition, 23-25 October 2024 Barcelona, Spania.
Advanced Gel Networks from Thiolated Chitosan and Cyclodextrin via Thiol-Ene Coupling.
Authors: Peptu, C.A.; Logigan, C.-L.; Delaite, C.; Tiron, C.-E.; Peptu, C.; Popa, M.