Fabrication of a Polysaccharide-Protein/Protein Complex Stabilized Oral Nanoemulsion to Facilitate the Therapeutic Effects of 1,8-Cineole on Atherosclerosis

Atherosclerosis (AS) is a systemic disease characterizedby lipiddeposition in the blood vessel wall that urgently requires effectiveand safe therapeutic drugs for long-term treatment. An essential oilmonomer-1,8-cineole (CIN) with ameliorative effects on vascular injurieshas considerable potential for preventing the progression of AS becauseof its antioxidant, anti-inflammation, and cholesterol regulatoryeffects. However, the high volatility and instability of CIN resultin low oral bioavailability and a short half-life, thereby limitingits clinical application. We formulated a nanoemulsion using a polysaccharide-protein/proteincomplex (dextran-bovine serum albumin/protamine, DEX5k-BSA/PTM)as an emulsifier, with vitamin B12 (VB12) as the ligandto facilitate the transportation across the small intestine. An emulsionpreparation method using a microjet followed by ultraviolet irradiationwas developed to obtain the CIN-loaded oral nanoemulsion CIN@DEX5k-BSA/PTM/VB12. The nanoemulsion improved the stabilityof CIN both in vitro and in vivo, prolonged the retention time in the gastrointestinal tract (GIT),and enhanced the permeability across the mucus layer and intestinalepithelial cells to increase oral bioavailability and plaque accumulationof CIN. Validated in an AS mouse model, CIN@DEX5k-BSA/PTM/VB12 achieved prominent therapeutic efficacy combating AS. Thisstudy highlights the advantages of DEX5k-BSA/PTM and VB12 in the development of nanoemulsions for CIN and providesa promising oral nanoplatform for the delivery of essential oils.