Development of a Multi-Compartmental Oral Vaccine Delivery System

Background: There is significant interest in the development of oral vaccine delivery systems, with the opportunity to access the body’s immune system. Recently, the use of multi-compartmental systems to deliver vaccines has been investigated. Objective: Here, we report on the development of a lipid-based multicompartmental system for oral vaccine delivery. Specifically, the system is based on a water-in-oil-in-water (W1/O/W2) double emulsion (DE) prepared with triglyceride oil. Method: The W1/O/W2 double emulsion (DE) was prepared using a 2-stage homogenization process, with nanostructured (hydrogel or liposome) carriers loaded into the internal (W1) phase along with model antigen, ovalbumin. Physicochemical characterization of the multicompartmental system included particle size, zeta potential, confocal microscopy, along with in vitro ovalbumin release studies. In vivo studies were undertaken using 6-8 week old female OT-I and OT-II mice (C57Bl/6J). Results: The DE formulation was optimized with respect to the internal (W1) phase stability as well as demonstrating the multi-compartmental structure of the system (confocal and cryo-SEM and in vitro release studies). Finally, the delivery system performance was determined in vivo, following oral vaccination of C57Bl/6 mice with model antigen (ovalbumin) and adjuvants, with the induction of a humoral immune response observed. Conclusion: A double emulsion-based multi-compartmental subunit vaccine delivery system has been successfully prepared and characterized, and demonstrated induction of an immune response following oral delivery.