TY - JOUR
T1 - Immunostimulatory biodegradable implants containing the adjuvant Quil-A--Part I
T2 - Physicochemical characterisation
AU - Myschik, Julia
AU - Eberhardt, Friederike
AU - Rades, Thomas
AU - Hook, Sarah
PY - 2008
Y1 - 2008
N2 - Sustained-release vaccines offer the potential to reduce, or obviate, the need for repeated dosing of vaccines. In this study, we report the development and characterisation of sustained-release lipid implants that release immunogenic, self-assembling colloidal particles. Lipid implants consisting of cholesterol (CHOL), phosphatidylcholine (PC), the adjuvant Quil-A (QA) and the model antigen ovalbumin (OVA) were formulated and investigated using a variety of techniques. Transmission electron microscopy was utilised to demonstrate the release of colloidal structures from these implants over time. The nature of the colloidal particles varied depending on the ratio of QA:CHOL:PC. The release of the model antigen as well as its incorporation into the colloidal particles was investigated using a fluorescent tag covalently coupled to OVA and quantified using fluorospectrophotometry. The antigen release was modified by the incorporation of excess CHOL into the formulation and was not only dependent on the ratio of QA:CHOL:PC but also on the nature of the model antigen. Alteration of the hydrophobicity of the model antigen resulted in an increased incorporation into the colloidal structures. Surface changes of the implants were analysed using scanning electron microscopy. The implant formulations investigated in this study show a potential for the delivery of subunit vaccines.
AB - Sustained-release vaccines offer the potential to reduce, or obviate, the need for repeated dosing of vaccines. In this study, we report the development and characterisation of sustained-release lipid implants that release immunogenic, self-assembling colloidal particles. Lipid implants consisting of cholesterol (CHOL), phosphatidylcholine (PC), the adjuvant Quil-A (QA) and the model antigen ovalbumin (OVA) were formulated and investigated using a variety of techniques. Transmission electron microscopy was utilised to demonstrate the release of colloidal structures from these implants over time. The nature of the colloidal particles varied depending on the ratio of QA:CHOL:PC. The release of the model antigen as well as its incorporation into the colloidal particles was investigated using a fluorescent tag covalently coupled to OVA and quantified using fluorospectrophotometry. The antigen release was modified by the incorporation of excess CHOL into the formulation and was not only dependent on the ratio of QA:CHOL:PC but also on the nature of the model antigen. Alteration of the hydrophobicity of the model antigen resulted in an increased incorporation into the colloidal structures. Surface changes of the implants were analysed using scanning electron microscopy. The implant formulations investigated in this study show a potential for the delivery of subunit vaccines.
U2 - 10.1080/10611860701848860
DO - 10.1080/10611860701848860
M3 - Journal article
C2 - 18365883
VL - 16
SP - 213
EP - 223
JO - Journal of Drug Targeting
JF - Journal of Drug Targeting
SN - 1061-186X
IS - 3
ER -