Modified microemulsions (MEs), termed by us nanodomains (NDs), seem to be suitable vehicles for dermal drug delivery due to their high surface area and the interface enriched with membrane recognizing agents, penetration enhancers, and other components. However, liquid nanodomains do not provide a controlled release of the bioactive through the skin. Therefore, the main goal of our present study is to develop a film polymeric platform embedded with liquid nanovehicles for the controlled release of drugs. This study provides a fundamental understanding of the main challenges of the preparation of special films capable of embedding nanodomains without destroying them. We describe film formation from & ldquo;nanodomains destructive polymers & rdquo; causing coalescence of the nanodroplets followed by structural failure compared to the formation from & ldquo;constructive polymer & rdquo; leading to the homogeneous, transparent films with a high loading capacity of nanodomains (up to 90 wt%). Using various fundamental structural techniques, we found that the film-forming process and its redissolution suggest the reconstitution of nanodomains with original structure and similar droplet size diameter ca. 12 nm. Additionally, thermal behavior studies demonstrated that the film does not have & ldquo;free & rdquo; or & ldquo;bulk & rdquo; water compared to welldefined free water peaks in liquid nanodomains systems. The embedded film with drug-loaded nanodomains offers a significant advantage as a drug delivery platform for controlled release long-term therapy. CO 2021 Elsevier Inc. All rights reserved.