In vivo investigation of twin-screw extruded lipid implants for vaccine delivery.

Sustained release systems have become the focus of attention in vaccine delivery as they may reduce or prevent the need for repeated dosing. In this work, lipid implants were prepared by twin-screw extrusion and investigated as vaccine delivery systems in vivo. The lipid implants consisted of cholesterol, soybean lecithin, and Dynasan 114. Ovalbumin (OVA) was employed as a model antigen and Quil-A (QA) as an adjuvant. In addition, OVA and QA loaded liposomes were prepared by the lipid-film hydration method, freeze-dried and then added to the lipid matrix prior to extrusion. Implants were administered subcutaneously and the kinetics of antigen release as well as the overall immune response stimulated were analysed by measuring CD4(+) and CD8(+) T cell proliferation, OVA-specific IgG production as well as cytokine (IFN-γ and IL4) secretion. Vaccine release from the implants was completed by 14 days. Inclusion of adjuvant into the implants was required for the generation of cellular and humoral immune responses. Inclusion of liposomes into the implant did not enhance the resulting immune responses generated.

Even MP ，Young K ，Winter G ，Hook S ，Engert J ... -  《-》

Immunostimulatory lipid implants containing Quil-A and DC-cholesterol.

Myschik J ，McBurney WT ，Rades T ，Hook S ... -  《INTERNATIONAL JOURNAL OF PHARMACEUTICS》

Chitosan hydrogels containing liposomes and cubosomes as particulate sustained release vaccine delivery systems.

Gordon S ，Young K ，Wilson R ，Rizwan S ，Kemp R ，Rades T ，Hook S ... -  《-》

Impact of implant composition of twin-screw extruded lipid implants on the release behavior.

The development of vaccine delivery systems that will remove or reduce the need for repeated dosing has led to the investigation of sustained release systems. In this context, the duration of antigen release is of great importance as is the requirement for concomitant adjuvant release. In this work, lipid implants consisting of cholesterol (CHOL), soybean lecithin, Dynasan 114 (D114), the model antigen ovalbumin (OVA) and the adjuvant Quil-A (QA) were produced by twin-screw extrusion. The release of antigen and adjuvant was investigated in vitro and we observed complete OVA release over a period of 7 days while QA was released in a linear fashion over a period of up to 12 days. In order to extend OVA release, lipid implants were subjected to post-extrusion curing at 45-55°C. The OVA release could be extended to up to 14 days. Furthermore the influence of the implant composition on the release of the model antigen was investigated. It was shown that the percentage of cholesterol in particular plays an important role in modulating release.

Even MP ，Bobbala S ，Kooi KL ，Hook S ，Winter G ，Engert J ... -  《-》

Immunostimulatory biodegradable implants containing the adjuvant Quil-A--Part II: In vivo evaluation.

Myschik J ，McBurney WT ，Hennessy T ，Phipps-Green A ，Rades T ，Hook S ... -  《-》