# Electrosprayed Core-Shell Microparticles as a Pulsatile Vaccine Delivery Platform

> **NIH NIH R03** · RICE UNIVERSITY · 2021 · $72,948

## Abstract

PROJECT SUMMARY/ABSTRACT
Every year an estimated 19.4 million children do not receive the set of vaccines recommended by the World
Health Organization, leading to 1.5 million vaccine-preventable deaths.1,2 A majority of undervaccinated children
live in low- and middle-income countries and often have limited access to healthcare.2,3 Nearly 6 million of these
children receive at least one vaccine dose, but remain at risk because they have not completed the full dosing
regimen.4,5 A vaccination method that delivers all doses of a vaccine, or multiple vaccines, in a single injection
would enable children with even one-time access to healthcare to be fully protected from the corresponding
infectious disease. Unfortunately, most controlled-release drug delivery systems exhibit continuous release
kinetics, which is vastly different from traditional soluble vaccines administered in multiple discrete doses over a
course of months. One recent study has described the development of biodegradable microparticle platform with
a polymer shell encapsulating a vaccine-loaded core that exhibits delayed, pulsatile release after a period
determined by the polymer degradation rate.6 By injecting patients with a mixed population of particles with
different degradation rates, vaccine can be released as discrete pulses, thereby mimicking traditional vaccination
schedules known to be safe and effective. Unfortunately, the original microparticle production method negatively
affects antigen stability, requires the use of large-gauge needles, and is low-throughput. This project seeks to
overcome these challenges by preparing microparticles using coaxial electrospraying, a single-step fabrication
process that can produce a single aqueous, vaccine-loaded core surrounded by a shell of polymer. This proposal
first aims to create small core-shell microparticles with dense polymeric shells that demonstrate the delayed,
pulsatile release of macromolecules in vitro and in vivo. Fluorescently tagged proteins will be used as model
vaccines to study the effects of particle size, shell density, relative wall thickness, and post-processing on release
kinetics. After identifying formulations that achieve pulsatile release, we will then optimize processing conditions
to maximize encapsulated antigen stability. An enzymatic reporter and a pH-sensitive dye will be added to the
core and tested at several stages of the particle life cycle to monitor microenvironmental conditions during
fabrication, storage, and release. Electrospraying materials and parameters will be adjusted to minimize changes
to protein conformation that could result from solvent interactions, thermal instability, and particle acidification,
which may affect the immune system's ability to create neutralizing antibodies. Although further optimization will
be required to fine-tune conditions for specific vaccines, this project will provide a framework for quickly
developing controlled-release vaccine formulations. Ultimatel...

## Key facts

- **NIH application ID:** 10195135
- **Project number:** 1R03EB031495-01
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Kevin James McHugh
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $72,948
- **Award type:** 1
- **Project period:** 2021-03-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195135

## Citation

> US National Institutes of Health, RePORTER application 10195135, Electrosprayed Core-Shell Microparticles as a Pulsatile Vaccine Delivery Platform (1R03EB031495-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10195135. Licensed CC0.

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