4 different macroemulsifiers with different stimuli responsiveness were designed: non-, pH-, enzyme- and dual-responsive. The same macroemulsifiers were used to encapsulate either hydrophilic (dipotassium glycyrrhizate or hyaluronic acid) or lipophilic actives (curcuma extract, ceramide and retinyl palmitate). Because the success of the nanoencapsulation technology, a PCT patent was submitted to protect it. Nanocapsules demonstrated the suitability to efficiently protect sensible active ingredients; retinyl palmitate degradation under UV light and oxygen was delayed from few days to several weeks. Stimuli responsiveness was also demonstrated. pH-responsive nanocapsules suffered a complete burst at pH values close to 7.4 while enzyme-responsive nanocapsules were destroyed in the presence of MMP2 or MMP9 metalloproteinases. Both macroemulsifier production and encapsulation processes were validated at pilot scale. Two competitive processes were studied for nanocapsules production: high pressure homogenizer (HPH) and tubular flow membrane contractor (TMC). Because the higher economic viability and maturity, HPH was finally selected. However, the novelty of TMC process to produce any type of nanoemulsions was demonstrated and disseminated in two articles (one published, one accepted). A Pilot Plant working under GMP (checked by means or an external audit) was established at the coordinator’s facilities. Nanocapsules penetration was studied in healthy and damaged skin models. It was demonstrated that the macroemulsifier and the encapsulated actives remained in the epidermis. None of the capsules produced showed skin irritation. The efficacy of nanocapsules in the treatment of damaged skin was demonstrated for three different skin conditions. Technology was able to reduce cellular damage by at least 30% and encapsulation increased up to 4 fold actives anti-inflammatory effect. Other actives such as ceramide presented unexpected anti-inflammatory properties. Safety of macroemulsifiers and nanocapsules was demonstrated by means of several toxicity and ecotoxicity experiments. All the new products developed were demonstrated to be safe. Characterization gaps having certain relation with nanomaterials safety were identified, such as limitations when characterizing nanomaterials dispersed in a non-aqueous media. Different protocols were proposed for size and toxicity measurements under those conditions. An in silico model now available in CORAL website was developed for toxicological prediction. The software was further adapted for the risk assessment of any type of organic/polymer based nanoparticles. 18 papers/books related with the model were published in open-access. The project was further disseminated via website and events (15 scientific conferences and 1 professional). With the aim of commercializing the technology a new brand identity was created: EMISSARY, first presented in the industrial show In-Cosmetic Global 2018. According to the business plan, the best way of exploitation of the technology was the creation of a spin-off company, EMISSARY Cosmetics, which is expected to start its activity by 2019. The company will offer on-the-shelf products and individualized encapsulation services who own their ingredient to encapsulate.
