A group of researchers from the Center for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC) has elaborated a novel formulation for the delivery of molecules that may be highly useful for the treatment of acute skin lesions.
In the last years, some strategies for drug delivery have been coming using non-coding RNA sequences – tiny sequences from the human genetic code with a regulatory role in our organism – for the treatment of various skin diseases. However, these strategies have had high difficulties, attending to the sensitive characteristics of these molecules and their difficulty to enter our skin cells.
“We wanted to develop a formulation that could deliver non-coding RNA in a more efficient manner. There is a wide class for new therapies that haven’t been working: first, there are enzymes in our skin that degrade external genetic material; second, molecules as big as these have difficulty to penetrate skin cells, and to act, they have to be integrated. A tool that makes this delivery possible is needed”, refers Josephine Blersch, CNC-UC researcher and first author of the study.
“Other FDA-approved formulations have high toxicity and a strong immunological response. Therefore, it is need that this tool has fast absorption and efficacy, without promoting unwanted responses. This way, we decided to develop a formulation that could sensitive to light, allowing control on the location and time of the delivery”, explain the researcher.
The study, published on Angewandte Chemie International, a German science journal in the field of chemistry, demonstrated the development of an innovative platform for the delivery of these sequences, better than the ones currently existent in the market, for application on skin diseases. To accomplish this, the researchers looked for formulations based on nanoparticles, that would be biodegradable, organic, and would cause low-to-none toxicity. This way, they started with the development of a nanoparticles library that would have these features, and would be activated by light, meaning, would release the carrying materials within cells, before they would be expelled by them.
“Firstly, we looked to develop a nanoparticle library with a physical and chemical diversity. Then, we wanted to filter the best formulations, using automatized microscopy, machine-learning algorithms, among other high throughput methods”, add Vítor Francisco, also CNC researcher and study author.
“We identified around 160 formulations, whose action would be controlled by light. We observed that 6 of these formulations were pretty faster and more efficient that a great fraction of the current formulations available on the market”, refers.
Initially, researchers tested these different formulations in skin cells, and observed a fast delivery and entry of the ARN molecule they were carrying after light stimulation. Then, with a ARN with an innovative active principle, they observed an acceleration of the wound healing in animal models with severe skin lesions. In the future, the group of researchers would like to test these same formulations on other contexts of acute skin lesions.
“This material has presented highly promisor with a local and topical application on the skin, or other tissue where light blue can be used a stimulus. This type of formulation might be highly useful in the treatment of severe skin lesions, associated to other types of diseases with a high world prevalence, such as type 2 diabetes, psoriasis, or other inflammatory pathologies. We would like to test in animal models of these disease”, affirms Josephine Blersch.
“With this study we wanted to develop formulations that could be controlled in order to diminish possible collateral effects and that, at the same time, increase the intracellular efficacy of the released material. It is the big advantage of this study: we both release their content, but also control this release. It could have a big impact in the future”, concludes Vítor Francisco.
Other than Josephine Blersch and Vítor Francisco, this study was coordinated by Lino Ferreira, CNC group leader, and had the participation of Catarina Rebelo, Adrian Jiménez-Balsa, Helena Antunes, Sandra Ponto and Susana Simões, also CNC researchers.
The work was financed by the Marie Curie Actions, through the International Training Network (ITN) NanoDrug, by the ERA Chair project, by the Foundation for Science and Technology, and by the Foundation for Regional Development (FEDER) through the project LIghtBRARY. The study, entitled “A light-triggerable nanoparticle library for the controlled release of non-coding RNAs”, may be consulted in http://dx.doi.org/10.1002/anie.201911398
Credits: Cristina Pinto, João Cardoso, Josephine Blersch, Lino Ferreira and Vítor Francisco