Formulation and evaluation of particulate systems for targeted delivery of vaccines

Abstract

The thesis introduction includes a literature survey of various conventional and experimental vaccination concepts including DNA vaccines. The unmet challenges to current vaccination approaches are highlighted, and recent formulation approaches to develop future vaccines of improved safety and efficacy are previewed. These include: mucosal vaccination as non-invasive vaccination route, formulation with adjuvants, and particulate vaccine delivery systems with special emphasis on those intended for nasal immunization. The potential and limitations of both lipid based and polymer based particulate delivery systems for vaccines are addressed. The potential improved performance of hybrid lipid-polymer vaccine nanocarriers is introduced.

Aim of the thesis:

The aim of the thesis was to develop cationic lipid-polymer hybrid nanoparticulate carrier for nasal vaccine delivery. The hybrid carrier is intended to combine the benefits of cationic lipids in terms of high Ag/DNA binding capacity and efficient cellular uptake together with the physical and biological stability of PLA polymer based matrices. The use of selected lipids with potential immunoadjuvant effect was attempted in this thesis; namely the cationic cholesterol derivative 3[N­ (N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC) or a novel lipidic polylysine dendron (LLD). The nano-sized carriers are intended to provide better immune responses via the nasal route.