Designing self-nanoemulsifying delivery systems to enhance bioaccessibility of hydrophobic bioactives (nobiletin): Influence of hydroxypropyl methylcellulose and thermal processing

Emulsion-based delivery systems are widely utilized for encapsulation of hydrophobic bioactive compounds. However, they must be carefully designed to retain and stabilize the encapsulated components during storage, and to release them after ingestion. In the present work, the influence of hydroxypropyl methylcellulose (HPMC) addition and heat treatment on the retention and release of a model hydrophobic nutraceutical (nobiletin) in nanoemulsions prepared by self-emulsification was investigated. Physical stability was assessed by measuring nobiletin retention, crystal morphology, and droplet size during storage. Further, the bioaccessibility of nobiletin was evaluated using a simulated gastrointestinal model. The results indicated that the presence of HPMC in the aqueous phase improved the retention of nobiletin in the nanoemulsions, without promoting any physical instability. The saturation concentration of nobiletin in the nanoemulsions increased from 4.5 to 6.0 mg/mL in the presence of HPMC. Heating the nanoemulsions promoted rapid droplet coalescence above a critical temperature. The combination of HPMC addition and heat treatment increased the retention time of nobiletin in nanoemulsions. Neither HPMC addition nor heat treatment affected the bioaccessibility (around 85%) of nobiletin when it was fully dissolved in the nanoemulsions. However, when nobiletin was not fully dissolved in the nanoemulsions, HPMC addition (from 52 to 59% without heat treatment) and heat treatment (from 52% to 82% without HPMC and from 59% to 84% with HPMC) increased the bioaccessibility. These findings are useful for the rational design and fabrication of nanoemulsion-based delivery systems with high loading efficiency and good release characteristics.