Chronic wounds, defined as those skin lesions exhibiting a delayed or impaired healing, represent a silent epidemic that affects a wide portion of the population. Thus, such wounds result in a major challenge to the public health and a significant economic burden. In this regard, the administration of growth factors (GF), such as epidermal growth factor (EGF), results a promising strategy for the treatment of chronic wounds. nevertheless, due to the low stability these proteins have shown at the wound area, the administration of GF involved in the healing process has shown limited success. bearing this in mind, the main objectives of this doctoral thesis is the development of a novel drug delivery system for the EGF, based on micro and nanoformulations, in order to improve the effectiveness of the commercialised Heberprot (a lyophilised powder containing 75 ug of Free rhEGF, administered 3 times weekly by intralesional injections).

The specific goals of thr present piece of work are the following:

-To design and optimise rhEGF-loaded biodegradable PLGA-Alginate microspheres and to assess their effectives in a full-thickness diabetised Wistar rats after their single intralesional administration.

-To develop rhEGF-loaded lipid nanoparticles for topical administration and to asses their effectiveness in healing impaired db/db mice.

- To test the effectiveness of the rhEGF-loaded optimised nanoformulations nanostructured lipid carriers (rhEGF-NLC) in a more relevant preclinical model, large white pigs.

-To design an integrated wound dressing-delivery systems using different vehicles, in order to make easier the topical administration of the developed rhEGF-loaded lipid nanoparticles, and to study the performance of theses dressings in an ex vivo pig skin model.