Exploratory Project funded by Fundação para a Ciência e a Tecnologia
Bioinspired materials in nanosolutions to tackle atopic dermatitis
Abstract | EXPL/BTM-MAT/0112/2021
BIOMATNANO4AD
THE STARTING POINT
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Atopic dermatitis (AD) is the biggest threat among skin conditions in terms of causing patients’ disability and its prevalence is still rising every day. A hallmark of AD is the epidermal barrier dysfunction due to abnormal lipid metabolism causing alterations in the ceramides and fatty acid profiles. Gold standard approaches to treat AD include the daily administration of topical emollients together with the reactive administration of glucocorticoids (GC) during the crisis. This therapeutic approach is farfrom ideal due to corticophobia and the safety issues of GC therapy. In this context, the proactive regimen is gaining more and more followers, comprising the long-term and low-dose administration of GC and emollients in pre-lesional areas. Sustainable technological approaches are hot topics in R&D&I and in current European Union and UnitedNations development policies. Europe needs locally produced biomaterials as the basis for innovative formulations, among which Hermetia illucens larvae oil seems to be particularlypromising to tackle AD due to its fatty acid composition. Moreover, biobased ionic liquids are recognized as green functional materials with great potential to be applied in drugdelivery systems. Lipid-based nanocarriers seem to be the most suitable platform, due to skin compatibility, to combine these biomaterials with barrier enhancingceramides in order to ultimately deliver emollients and low-dose GC in a cutting-edge formulation to tackle AD.
THE STRATEGY FOR INNOVATION
BIOMATNANO4AD aims to fulfil thecurrent needs in AD management through a bioinspired, nanotechnological, and sustainable approach combining multifunctional biomaterials in lipid-based nanocarriers that cansynergically perform as GC delivery systems and topical emollients. The pentagonal coalition of ceramides, insect oil, ionic liquids, nanotechnology, and glucocorticoids in aninnovative multifunctional nanoformulation will allow overcoming existing therapeutic limitations of AD. The product development strategy will be based on the initial optimizationand characterization of lipid-based nanocarriers, followed by enhancement of nanosystem performance using biobased ionic liquids. The optimized nanosystems by quality-by-design (QbD) strategies will then proceed to in vitro and in vivo safety assessments. Finally, the efficacy of biocompatible nanoformulations will be tested through in vitro and in vivomethodologies. At the end of BIOMATNANO4AD, it is expected that at least one nanoformulation will have reached a preclinical stage, with potential to make a significantcontribution towards a cost-effective treatment to ultimately upgrade the quality of life for AD patients.
THE RIGHT KNOW-HOW
The accomplishment of the ambitious objectives of BIOMATNANO4AD will be ensured by the know-how of a multidisciplinary team of CBIOS researchers and by the strategic collaborations with a biotech company (EntoGreen) and leading scientific institutions (LAQV and Vienna University). Expertise in the optimization of nanoformulations following a QbD approach decreases the risk and increases thecapacity to obtain a nanosystem with optimal stability characteristics, and an adequate safety and efficacy performance. Proficiency in taking full advantage of bioinspired products will be useful in the application of ceramides, insect oil, and ionic liquids in skin formulations. Finally, the advanced skills of the research team also enable the successful invitro and in vivo assessment of the cytotoxicity and bioactivity performances of the innovative formulations. Meticulously planned collaborations with partners ofexcellence have been established to further boost product development. This befitting team will also be dedicated to dissemination and communication activities so that the majorbreakthroughs of BIOMATNANO4AD can be shortly available for the scientific community, academia, pharmaceutical industry, patients’ associations, and general society.
Research
Team
Catarina Pereira Leite
Principal Investigator
ORCID: 0000-0001-5407-3983
Catarina Rosado
Co-Principal Investigator
ORCID: 0000-0002-6429-6213
Nuno Saraiva
Research Team Member
ORCID: 0000-0003-1333-9137
Ana Júlio
Research Team Member
ORCID: 0000-0002-3129-6495
Rossana Roque
First Stage Researcher
CIÊNCIA ID: D814-ABE2-CEAF
Cíntia
Almeida
PhD Student
ORCID: 0000-0002-9101-618
João
Vieira
PhD Student
ORCID: 0000-0002-8718-2083
Scientific outputs
List of publications
1. Almeida, C., Filipe, P., Rosado, C., & Pereira-Leite, C. (2022). Nanodelivery Strategies for Skin Diseases with Barrier Impairment: Focusing on Ceramides and Glucocorticoids. Nanomaterials, 12(2), 275. doi:10.3390/nano12020275
2. Vieira, J., Castelo, J., Martins, M., Saraiva, N., Rosado, C., & Pereira-Leite, C. (2023). Mixed Edge Activators in Ibuprofen-Loaded Transfersomes: An Innovative Optimization Strategy Using Box-Behnken Factorial Design. Pharmaceutics, 15(4), 1209. doi:10.3390/pharmaceutics15041209
3. Pereira-Leite, C., Bom, M., Ribeiro, A., Almeida, C., & Rosado, C. (2023). Exploring Stearic-Acid-Based Nanoparticles for Skin Applications - Focusing on Stability and Cosmetic Benefits. Cosmetics, 10(4), 99. doi:10.3390/cosmetics10040099
List of communications
Communications in international scientific meetings:
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1. Pereira-Leite, C. Nano-inovação em veiculação transcutânea. Congresso Farmacêutico de São Paulo. November 13th 2021 (virtual). Oral communication.
2. Almeida, C., Filipe, M. S., Rijo, P., Pereira-Leite, C., Rosado, C. Using lipids extracted from black soldier fly larvae for nanoparticles development - Preliminary studies. II Bio.Natural – Bioactive Natural Products Research Meeting. November 18-19th 2021 (virtual). Poster.
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3. Júlio, A., Costa, J.G., Pereira-Leite, C., Santos de Almeida, T. Ionic liquids as a bridge to develop new TransfersomILs systems. Global Conference on Nanotechnology. June 21-24th 2022 (virtual). Oral communication.
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4. Júlio, A., Costa, J.G., Pereira-Leite, C., Santos de Almeida, T. TransfersomILs: an innovative combination between Transfersomes and Ionic Liquids. InnovDelivery’22 - I Lusophone Meeting on Innovative Delivery Systems. June 30th 2022 (virtual). Oral communication.
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5. Almeida, C. Rosado, C. Pereira-Leite, C. Development of lipid nanoparticles from Hermetia illucens larvae extract for dexamethasone delivery for topical application. InnovDelivery’22 - I Lusophone Meeting on Innovative Delivery Systems. June 30th 2022 (virtual). Oral communication.
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6. Júlio, A., Reis, A., Martins, I., Pereira-Leite, C., Santos de Almeida, T. Impact of the loaded phytochemical on TransfersomILs performance. InnovDelivery’22 - I Lusophone Meeting on Innovative Delivery Systems. June 30th 2022 (virtual). Poster.
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7. Vieira, J., Castelo, J., Martins, M., Saraiva, N. Optimization of Ibuprofen-loaded Transfersomes for Transcutaneous Delivery. InnovDelivery’22 - I Lusophone Meeting on Innovative Delivery Systems. June 30th 2022 (virtual). Oral communication.
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8. Pereira-Leite, C., Almeida, C., Júlio, A., Vieira, J., Costa, J.G., Santos de Almeida, T., Rosado, C. From sustainable materials to innovative lipid nanocarriers. Global Virtual Summit on Nanoscience & Nanotechnology. July 1-2nd 2022 (virtual). Oral communication.
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9. Almeida, C. Rosado, C. Pereira-Leite, C. Nanodelivery strategies based on lipids obtained from larvae biomass for skin diseases related with barrier impairment. 3rd EpiLipidNET general Action meeting - Pan-European Network in Lipidomics and EpiLipidomics. September 21-23rd 2022. Aveiro, Portugal. Oral communication.
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10. Júlio, A., Almeida, C., Vieira, J., Roque, R., Rosado, C., Pereira-Leite, C. Improving the performance of SLNs - combining lipids extracted from larvae biomass and choline-based ILs. 5º Encontro de Biotecnologia Medicinal/2nd Iberian Congress on Medicinal Biotechnology. October 21st 2022. Escola Superior de Saúde do Instituto Politécnico do Porto, Porto, Portugal. Poster.
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11. Júlio, A., Roque, R., Vieira, J., Almeida, C., Reis, A., Costa J.G., Saraiva, N., Santos de Almeida, T., Rosado, C., Pereira-Leite, C. Boosting the lipid-based nanosystems performance using ionic liquids. 2nd Global Virtual Summit on Nanoscience & Nanotechnology. November 11-12nd 2022 (Virtual). Oral communication.
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12. Júlio, A., Roque, R., Martins, M., Martinho, M.T., Saraiva, N., Costa, J.G., Rosado, C., Pereira-Leite, C. Exploring the innovative TransfersomILs for the cutaneous delivery of hydroxycinnamic acids. 4th SPLC-CRS Young Scientists Meeting. February 6-7th 2023. i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal. Poster.
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13. Vieira, J., Rosado, C., Pereira-Leite, C. Optimization of rutin-loaded cerosomes: a step forward for the management of dermatological conditions. 4th SPLC-CRS Young Scientists Meeting. February 6-7th 2023. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. Poster.
14. Júlio, A., Roque, R., Martins, M., Martinho, T., Costa, J.G., Saraiva, N., Rosado, C., Pereira-Leite, C. TransfersomILs: an innovative nanosystem for the cutaneous delivery of hydroxycinnamic acids. NanoMed Europe 2023. June 19-22nd 2023. University of Liverpool, Liverpool, Reino Unido. Poster.
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15. Júlio, A., Roque, R., Almeida, C., Vieira, J., Saraiva, N., Rosado, C., Pereira-Leite, C. Combining lipids extracted from larvae biomass and biobased ionic liquids to boost skin nanodelivery. NanoMed Europe 2023. June 19-22nd 2023. University of Liverpool, Liverpool, Reino Unido. Poster.
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16. Pereira-Leite, C., Almeida, C., Roque, R., Júlio, A., Santos, C., Gingado, M., Saraiva, N., Rosado, C. From insect larvae biomass to lipid-based nanocarriers: an advanced approach for the management of atopic dermatitis. NanoMed Europe 2023. June 19-22nd 2023. University of Liverpool, Liverpool, Reino Unido. Poster.
17. Júlio, A., Roque, R., Martins, M., Martinho, T., Costa, J.G., Saraiva, N., Rosado, C., Pereira-Leite, C. TransfersomILs: a biobased strategy for the skin delivery of hydroxycinnamic acids. III Bio.Natural – Bioactive Natural Products Research Conference. July 13-14th 2023. Universidade Lusófona, Lisboa, Portugal. Oral Communication.
18. Pereira-Leite, C., Roque, R., Almeida, C., Júlio, A., Vieira, J., Martins, M., Guerreiro, I., Fernandes, A.S., Saraiva, N., Rosado, C. Cell-based models to study the safety of lipid nanoparticles - surfactant location matters? 2nd NETSKINMODELS Meeting, CA21108, September 13-15th 2023. Porto, Portugal. Oral communication.
19. Pereira-Leite, C., Almeida, C., Roque, R., Júlio, A., Saraiva, N., Rosado, C. Lipidic nanocarriers based on insect biomass to tackle atopic dermatitis. APGI Skin & Formulation. 6th Symposium. October 2-3rd 2023. Nantes, France. Oral communication.
20. Pereira-Leite, C., Almeida, C., Roque, R., Júlio, A., Saraiva, N., Rosado, C. Insect oil: a high value excipient for lipid-based nanocarriers to tackle atopic dermatitis. X Congresso Iberoamericano de Ciências Farmacêuticas, October 26-28th 2023. Coimbra, Portugal. Oral communication.
21. Júlio, A., Sultane, A., Viana, A.S., Rosado, C., Costa, J.G., Mota, J.P., Santos de Almeida, T., Pereira-Leite, C. Ionic liquids: game changers for the development of controlled delivery systems? 9th International Electronic Conference on Medicinal Chemistry. November 1-30th 2023. (Virtual). Oral communication.
22. Vieira, J., Castelo, J., Guerreiro, Í., Martins, M., Rodrigues, M., Fernandes, A.S., Saraiva, N., Rosado, C., Pereira-Leite, C. Single or Mixed edge activators: a shift in transfersomes properties? 9th International Electronic Conference on Medicinal Chemistry. November 1-30th 2023. (Virtual). Oral communication.
23. Almeida, C.; Murta, D.; Nunes, R.; Baby, A.; Fernandes, A..; Barros, L.; Rijo, P.; Pereira-Leite, C.; Rosado, C. On the path to innovative nanotechnological formulations for skin diseases associated with barrier impairment. 9th International Electronic Conference on Medicinal Chemistry. November 1-30th 2023. (virtual). Poster.
24. Júlio, A., Roque, R., Sultane, A., Reis, A., Martins, I.*, Martins, M.*, Martinho, T.*, Viana, A.S., Saraiva, N., Costa, J.G., Rosado, C., Mota, J.P., Santos de Almeida, T., Pereira-Leite, C. Are ionic liquids key materials in the development of controlled drug delivery systems? 7th International Conference on Ionic Liquid-based Materials - ILMAT, November 21-24th 2023. Instituto de Pernambuco, Porto, Portugal. Oral communication.
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Communications in national scientific meetings:
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1. Pereira-Leite, C., Bom, M., Ribeiro, A., Almeida, C., Rosado, C. Stratum corneum lipids as the basis of nanoparticles for epidermal regeneration. COSMETINNOV - V Congresso da Sociedade Portuguesa de Ciências Cosmetológicas. March 10-11th 2022, Lisboa, Portugal. Poster.
2. Almeida, C., Pereira-Leite, C., Rosado, C. Development of lipid nanoparticles based on insect larvae biomass for skin delivery. COSMETINNOV - V Congresso da Sociedade Portuguesa de Ciências Cosmetológicas. March 10-11th 2022, Lisboa, Portugal. Poster.
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3. Almeida, C., Pereira-Leite, C., Rosado, C. Lipid nanoparticles based on insect larvae biomass for skin application. Encontro Ciência’22. May 16-18th 2022, Centro de Congressos de Lisboa, Lisboa, Portugal. Poster.
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4. Almeida, C., Rosado, C., Pereira-Leite, C. Bio-based lipid nanoparticles obtained from insect larvae biomass extract for skin diseases with barrier impairment. 2ª edição do Sunset Skin Summit: Sustentabilidade no Tratamento e Cuidado da Pele. October 26-27th 2022 (virtual). Oral communication.
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5. Almeida C, Roque R, Saraiva N, Pereira-Leite C, Rosado C. New perspectives in the approach to skin barrier dysfunction - using lipid nanoparticles based on insect biomass to improve dexamethasone delivery. 2nd International Meeting of the Portuguese Society of Physiology. November 11-12nd 2022. Coimbra, Portugal. Poster.
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6. Júlio, A., Reis, A., Roque, R., Saraiva, N., Costa, J.G., Rosado, C., Santos de Almeida, T., Pereira-Leite, C. Probing the impact of TransferomILs containing rutin in skin physiology - cytotoxicity studies. 2nd International Meeting of the Portuguese Society of Physiology. November 11-12nd 2022. Escola Superior de Tecnologia da Saúde do Politécnico de Coimbra, Coimbra, Portugal. Poster.
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7. Júlio, A., Roque, R., Saraiva, N., Rosado, C., Costa, J.G., Santos de Almeida, T., Pereira-Leite, C. Exploring the possibilities of TransfersomILs in sparingly soluble drugs - the case of rutin. 53rd Meeting of the Portuguese Society of Pharmacology. 41st Meeting of Clinical Pharmacology and 22nd Meeting of Toxicology - SPF 2023. February 1-3rd 2023. Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal. Oral communication.
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8. Roque, R., Almeida, C., Fernandes, A.F., Rosado, C., Pereira-Leite, C., Saraiva, N. Cytotoxicity assessment of innovative topical nanodelivery systems for atopic dermatitis. 53rd Meeting of the Portuguese Society of Pharmacology. 41st Meeting of Clinical Pharmacology and 22nd Meeting of Toxicology – SPF 2023. February 1-3rd 2023. Coimbra, Portugal. Oral communication.
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9. Pereira-Leite, C., Almeida, C., Roque, R., Júlio, A., Vieira, J., Santos, C., Gingado, M., Saraiva, N., Rosado, C. The BIOMATNANO4AD project: How long a way have we come? CBIOS Science Sessions. April 11th 2023. Lusófona University, Lisboa, Portugal. Oral communication.
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10. Roque, R., Almeida, C., Júlio, A., Santos, C., Gingado, M., Saraiva, N., Rosado, C., Pereira-Leite, C. Using insect larvae biomass to produce innovative lipid nanoparticles: a bioinspired and sustainable approach to tackle atopic dermatitis. Ciência 2023, July 5-7th 2023 (virtual). Poster.
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11. Pereira-Leite, C., Almeida, C., Júlio, A., Vieira, J., Roque, R., Turiel, C., Saraiva, N., Rosado, C. On the trail of biomaterial-based nanosolutions for skin health. V Jornadas CBIOS. November 10th 2023. Centro Universitário de Lisboa - Universidade Lusófona, Lisboa, Portugal. Oral communication.
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12. Almeida, C., Gingado, M., Santos, C., Pereira-Leite, C., Rosado, C. Further Exploring Solid Lipid Nanoparticles Based on the Lipid Fraction From Larvae Biomass Extract - In Vivo Safety and Efficacy Assays. V Jornadas CBIOS. November 10th 2023. Centro Universitário de Lisboa - Universidade Lusófona, Lisboa, Portugal. Oral communication.
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13. Martins, M., Martinho, T., Júlio, A., Pereira-Leite, C., Rosado, C. TransfersomILs loading caffeic or p-coumaric acids: An innovative approach for cutaneous delivery. V Jornadas CBIOS. November 10th 2023. Centro Universitário de Lisboa - Universidade Lusófona, Lisboa, Portugal. Poster.
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14. Júlio, A., Rosado, C., Pereira-Leite, C. TransfersomILs for the skin delivery of ferulic acid: impact on permeation assays? V Jornadas CBIOS. November 10th 2023. Centro Universitário de Lisboa - Universidade Lusófona, Lisboa, Portugal. Poster.
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15. Santos, C., Gingado, M., Pereira-Leite, C., Rosado, C. Development of gels incorporating nanoemulsions based on Hermetia illucens larvae extract: stability and skin compatibility studies. V Jornadas CBIOS. November 10th 2023. Centro Universitário de Lisboa - Universidade Lusófona, Lisboa, Portugal. Poster.
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Acknowledgements
This project was funded by Fundação para a Ciência e a Tecnologia (http://doi.org/10.54499/EXPL/BTM-MAT/0112/2021).