Immunostimulatory biodegradable implants containing the adjuvant Quil-A--Part I: Physicochemical characterisation

Area of Science:

• Biomaterials Science
• Vaccine Technology
• Nanotechnology

Background:

• Repeated vaccine dosing presents challenges in vaccine administration and patient compliance.
• Sustained-release vaccine formulations aim to improve efficacy and reduce dosing frequency.
• Lipid-based delivery systems offer a promising platform for controlled antigen release.

Purpose of the Study:

• To develop and characterize sustained-release lipid implants for vaccine delivery.
• To investigate the release of immunogenic, self-assembling colloidal particles from these implants.
• To evaluate the potential of these implants for subunit vaccine delivery.

Main Methods:

• Formulation of lipid implants using cholesterol (CHOL), phosphatidylcholine (PC), Quil-A (QA) adjuvant, and ovalbumin (OVA) model antigen.
• Transmission electron microscopy (TEM) to visualize colloidal particle release.
• Fluorescent tagging of OVA and fluorospectrophotometry to quantify antigen release and incorporation.
• Scanning electron microscopy (SEM) for surface analysis of implants.

Main Results:

• Lipid implants successfully released self-assembling colloidal structures over time.
• The nature of released colloidal particles varied based on the QA:CHOL:PC ratio.
• Antigen release was modulated by CHOL content and antigen hydrophobicity, with increased incorporation of hydrophobic antigens.
• Implant surface morphology was characterized by SEM.

Conclusions:

• Developed lipid implants demonstrate sustained release of immunogenic colloidal particles.
• Formulation parameters, including lipid ratios and antigen properties, significantly influence release kinetics and particle characteristics.
• These lipid implants show potential as a delivery system for subunit vaccines, reducing the need for frequent administration.