Poster W17 - Engineered MCM-48 nanoparticles as potential carriers for oral vaccine delivery

Saturday, October 26, 2024

10:00 AM - 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Chang Hee Min, PhD (he/him/his)

Researcher
Department of Biomedical Engineering, Seoul National University College of Medicine
Seoul, Republic of Korea

Co-Author(s)

SK

Se-Na Kim, PhD

Researcher
Department of Biomedical Engineering, Seoul National University College of Medicine, United States

Primary Investigator(s)

Young Bin Choy, PhD

Professor
Department of Biomedical Engineering, Seoul National University College of Medicine, Republic of Korea

Co-Author(s)

JH

Jooli Han, PhD

Assistant Professor
Department of Biomedical Engineering, Seoul National University College of Medicine, Republic of Korea
HK

Hongki Kang, PhD

Associate Professor
Department of Biomedical Engineering, Seoul National University College of Medicine, Republic of Korea

Introduction: Oral vaccination has been considered as a convenient strategy compared to other conventional methods such as injection. However, this approach poses some problems, such as low antigen stability through the gastrointestinal tract and low targeting efficiency to the action site. To overcome the limitations of oral vaccines, we employed and modified the pore-expanded MCM-48 nanoparticles (i.e. MCM-48-EP) as oral vaccine delivery carriers. To enhance for mucopenetration and improve delivery into the M cells, the active site of the oral vaccine, polyethylene glycol (PEG) was grafted onto the surface of the MCM-48-EP (i.e. the PEG-MCM-48-EP). To evaluate the performance of the PEG-MCM-48-EPs, ovalbumin (OVA) was used as a model antigen and loaded in the prepared particles (i.e., OVA@PEG-MCM-48-EP).

Materials and

Methods: MCM-48 was synthesized according to the modified stöber method, where the pores of the MCM-48 nanoparticle were expanded using dimethylhexadecylamine (DMHA). Then, PEG was grafted on the surface of particles. The PEG-coated particles were then loaded with OVA. The in vitro antigen release study was performed in the simulated gastrointestinal environment. In vivo immunogenicity experiments were conducted with eight-week-old female BALB/c mice. After an initial antigen administration, two additional doses were given at two-week intervals. Blood samples were collected ten weeks after the first administration to compare antibody (IgG, IgA) titers in the plasma. The M cell targeting efficacy was assessed under in vivo environments using the fluorescein-labelled PEG-MCM-48-EPs.

Results, Conclusions, and Discussions: The X-ray diffraction analysis results with the MCM-48 displayed a well-resolved pattern as previously reported. The nitrogen absorption/desorption data show that the surface area, pore volume, and average pore diameter indeed increased when the pores were expanded with DMHA. In case of OVA@PEG-MCM-48-EP, surface area, pore volume, and pore diameter is decrease, indicating that OVA was well-encapsulated within the pore structure. Fourier-transform infrared spectroscopy analysis showed that the C-H asymmetric peak of the methylene group was observed in both PEG-MCM-48-EP and PEG but not in the MCM-48-EP, confirming that PEG was coated on the particle surface. In vitro OVA release experiments indicated that OVA@PEG-MCM-48-EP retained over 75% of the antigen after the initial 2 hours and released the encapsulated antigen gradually over the next 48 hours. To evaluate the efficacy of the developed particles as oral vaccine delivery carriers, in vivo immunogenicity experiments were conducted on BALB/c mice. The group orally administered with OVA@PEG-MCM-48-EP showed IgG antibody titers similar to the group subcutaneously injected with OVA solution and significantly higher titers compared to the no treatment, orally administered OVA solution, and orally administered OVA@MCM-48-EP groups. For IgA antibody titers, indicating mucosal immune response, the group orally administered with OVA@PEG-MCM-48-EP showed significantly higher antibody titers than the other groups. The confocal microscopy image of mice Peyer’s patches revealed that the PEG-MCM-48-EP could be penetrated mucosal layer of gut wall and well localized in M cells.
Pore expanded MCM-48 was successfully synthesized, and the surface could be functionalized with PEG. The PEG-MCM-48-EP possessed a mucopenetration property, enhancing the likelihood of M cell internalization. Oral administration of OVA@PEG-MCM-48-EP facilitates effective antigen exposure to M cells, resulting in both systemic and mucosal immunization comparable to subcutaneous injections. Therefore, we conclude that the PEG-MCM-48-EP is a potential carrier for oral vaccine delivery.

Acknowledgements (Optional): This research was supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2021R1A2B5B03001914)