Tailoring Microemulsification Techniques for the Encapsulation of Diverse Cargo: A Systematic Analysis of Poly...

Cargo encapsulation through emulsion-based methods has been pondered over the years. Although several microemulsification techniques have been employed for the microcapsule's synthesis, there are still no clear guidelines regarding the suitability of one technique over the others or the impacts on the morphological and physicochemical stability of the final particles. Therefore, in this systematic study, we investigated the influence of synthesis parameters on the fabrication of emulsion-based microcapsules concerning morphological and physicochemical properties. Using poly(urea-formaldehyde) (PUF) microcapsules as a model system, and after determining the optimal core/shell ratio, we tested three different microemulsification techniques (magnetic stirring, ultrasonication, and mechanical stirring) and two different cargo types (100% TEGDMA (Triethylene glycol dimethacrylate) and 80% TEGDMA + 20% DMAM (N,N-Dimethylacrylamide)). The resulting microcapsules were characterized via optical and scanning electron microscopies, followed by size distribution analysis. The encapsulation efficiency was obtained through the extraction method, and the percentage reaction yield was calculated. Physicochemical properties were assessed by incubating the microcapsules under different osmotic pressures for 1 day and 1, 2, or 4 weeks. The data were analyzed statistically with one-way ANOVA and Tukey's tests (α = 0.05). Overall, the mechanical stirring resulted in the most homogeneous and stable microcapsules, with an increased reaction yield from 100% to 50% in comparison with ultrasonication and magnetic methods, respectively. The average microcapsule diameter ranged from 5 to 450 µm, with the smallest ones in the ultrasonication and the largest ones in the magnetic stirring groups. The water affinities of the encapsulated cargo influenced the microcapsule formation and stability, with the incorporation of DMAM leading to more homogeneous and stable microcapsules. Environmental osmotic pressure led to cargo loss or the selective swelling of the shells. In summary, this systematic investigation provides insights and highlights commonly overlooked factors that can influence microcapsule fabrication and guide the choice based on a diligent analysis of therapeutic niche requirements.