The development of freeze-dries liposome formulations as vaccine delivery systems

• Main Author: Yusuf, Helmy
• Published: Queen's University Belfast 2013
• Subjects: 615.372
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603300

There is interest in the use of freeze-dried liposomes as immunological adjuvants for vaccines. In this thesis the development of a novel freeze-dried liposomal formulation containing antigen that is stable and exhibits enhanced adjuvanting and delivery characteristics compared with conventional liposomes is described. The novel liposomes are comprised of cationic dimethyldioctadecylammonium (DDA), soy-phosphatidylcholine (SPC) and TPGS (D-α tocopherol polyethylene glycol 1000 succinate). DDA and TPGS have prospective advantages as vaccine carrier system as they reportedly enhance immunogenicity. Furthermore, the nature and versatility of well-designed liposomes can also be advantageous, whereas the freeze-dried liposomes potentially fulfil the stability requirements of an ideal vaccine. A systematic study was performed; from pre-formulation to in vivo examination to reveal the potency of the developed vaccine delivery systems. The DDA and SPC with certain concentration of TPGS exhibited good miscibility during dehydration and rehydration . The effect of the presence of the Iyoprotectant trehalose on the observed phase behaviour was also examined. The developed liposomal formulation comprised of these materials demonstrated good stability after freeze-drying process; size, zeta potential, encapsulation efficiency and sustained release profile. The dry products exhibited acceptable Tg and low water content. Further investigations revealed that the novel liposomes demonstrated better permeability across nasal mucosa, interaction with epithelial cells and higher cellular uptake when compared with conventional liposomes. The performed preliminary in vivo study revealed that the novel liposomal formulation induced the highest immune responses in both systemic and mucosal sites with a preference of Th2-type humoral immune response. Together, these data are indicative of the potency of the novel liposomes as vaccine delivery systems; where their freeze-dried form also offers additional benefit in terms of thermal stability that could be efficient in cost and useful in stock piling.