“The cover image represents a topical treatment of an open wound by spraying a suspension of nanoconjugates of a recombinant human epidermal growth factor (rhEGF) and nanovesicles, called Quatsomes, with the mission of completely and efficiently closing such an open wound with a painless therapy.” – Jaume Veciana

ICMAB Researcher Jaume Veciana from the Molecular Nanoscience and Organic Materials (NANOMOL) Group is one of the authors of this article that showcases a potential nanomedicine for the topical treatment of complex wounds based on nanoconjugates with the appropriate physicochemical properties as well as antimicrobial activity that aids in the prevention of infections. This nanomedicine is created through a soft, reliable, and scalable method based on compressed CO₂ for obtaining nanoconjugates of recombinant human epidermal growth factors and nanovesicles.

The cover

 Front cover in “Advanced Therapeutics” for the article “Recombinant Human Epidermal Growth Factor/Quatsome Nanoconjugates: A Robust Topical Delivery System for Complex Wound Healing”.

This novel nanomedicine presents many interesting attributes, like controlled and narrow nanoscopic particle size distribution, long-term stability, drug loading, drug release, drug protection, targeting ability, and bioactivity. A key aspect of how it works resides in its triple action, according to Jaume Veciana:

“1) An inbuilt antimicrobial activity preventing infections which are very frequent during the healing of open wounds, 2) Promoting the regeneration of granulation tissue and re-epithelialization with complete closure of complex wounds, and 3) Enabling a topical administration of the nanomedicine instead of using the infiltration painful treatments of rhEGF currently used.”

This medicine aims to aid in the reparation of chronic wounds which have an 80 % chance of bacterial colonization. Cases like diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), and pressure ulcers (PUs) strongly correlate with amputation and increased mortality. The objective of this treatment is to face the cases that fail to respond to reparative drug stimuli:

“Despite the benefits demonstrated by treatments based on biological molecules, like proteins, in improving small-sized and uncomplicated neuropathic ulcers, finding effective therapies that could reduce amputations in ischemic and complicated forms of neuropathic wounds like DFUs remains a challenge”, says Jaume Veciana. “The properties of the reported nanoconjugates in this article may overcome this challenge since the high topical effectiveness exhibited by the nanoconjugates in a few compassionate patients which were treatment with irrigation of a rhEGF@Quatsome dispersion on the ulcers significantly increased the incidence of a complete or higher than 80 % healing with only mild-to-moderate side-effects and remarkably no patient exhibited incidence of wound infection related adverse events associated with the ulcer.

In conclusion, such nanoconjugates fulfill the basic requirements, related to their production, storage stability, patient compliance, and high efficacy with minimal side effects, to be considered as a potential nanomedicine to enter in future clinical assays for the treatment of DFUs and presumably also of VLUs and PUs.”

The results hereby presented are the conclusion of the work of a very interdisciplinary team:

"We would like to stress that the research reported in this article was made by a large multidisciplinary team with experts on materials science, biology, pharmacology, medicine, physics, and chemical engineering belonging to two research centers, two private companies, one technological center, and one hospital who have performed all necessary efforts to develop a novel nanomedicine from the very beginning using a technology developed entirely at the ICMAB which soon may enter in clinical trials.”

Abstract of the paper

A multitude of microparticles and nanoparticles is developed to improve the delivery of different small drugs and large biomolecules, which are subject to several hindering biological barriers that limit their optimal biodistribution and therapeutic effects. Here, a soft, reliable, and scalable method based on compressed CO₂ is reported for obtaining nanoconjugates of recombinant human epidermal growth factor and nanovesicles called quatsomes, where the latter consists of cholesterol and cetyltrimethylammonium bromide.

These nanoconjugates exhibit appropriate values of the major critical quality attributes of colloidal nanomedicines, such as controlled and narrow nanoscopic particle size distribution (which play important roles in determining their stability), drug loading, drug release, drug protection, targeting ability, and bioactivity. Also, they exhibit a dual action by 1) inbuilt antimicrobial activity preventing infections and 2) promoting regeneration of granulation tissue and re-epithelialization with complete closure of complex wounds. Therefore, such nanoconjugates are a potential nanomedicine for the topical treatment of complex wounds, particularly diabetic foot ulcers and venous leg ulcers.

Reference:

Recombinant Human Epidermal Growth Factor/Quatsome Nanoconjugates: A Robust Topical Delivery System for Complex Wound Healing
Lidia Ferrer-Tasies, Hector Santana, Ingrid Cabrera-Puig, Elisabet González-Mira, Lídia Ballell-Hosa, Carla Castellar-Álvarez, Alba Córdoba, Josep Merlo-Mas, Haydee Gerónimo, Glay Chinea, Viviana Falcón, Evelyn Moreno-Calvo, Jan Skov Pedersen, Jessica Romero, Claudia Navarro-Requena, Calixto Valdés, Miladys Limonta, Jorge Berlanga, Santiago Sala, Eduardo Martínez, Jaume Veciana, Nora Ventosa
Advanced Therapeutics 2021, 4, 6, 2000260, 10.1002/adtp.202000260

On the Topic:

ICMAB Researcher Lídia Ballell from the Molecular Nanoscience and Organic Materials (NANOMOL) Group discussed this topic on her talk about the power of nanovesicles in the framework of the 10alamenos9 VI Nanoscience and Nanotechnology Festival "Vermú de nanociencia":