Thursday, March 8, 2012

Intravaginal Administration of Clodrosome (Clodronate encapsulated liposomes)

As with the nasal, pulmonary and other mucosal surfaces, the vaginal mucosum must defend the animal from invasion by external pathogens and other foreign particles. Therefore various immune-responsive phagocytic cells are present in order to remove and kill invading pathogens as well as to initiate antibody production to further protect the animal from future attacks whenever possible. Like all other phagocytic cells, vaginal phagocytes identify liposomes as foreign particles and remove them via phagocytosis. Internalized clodronate liposomes kill the phagocytes which will, in turn, release cytokines into the bloodstream thus recruiting new phagocytes to the site of the invasion. This means that the experimental protocol must take into account the fact that the depletion of the local phagocytes is temporary and additional systemic (i.p. or i.v.) clodronate liposome dosing will be necessary if prolonged vaginal phagocyte depletion is the goal.
Direct instillation of clodronate liposomes into the vagina has been reported in only 1 paper and until these results were published, it was only an assumption that local vaginal phagocytes (macrophages and dendritic cells) could be depleted by direct intravaginal instillation of clodronate liposomes. Although not addressed specifically in this paper, it is a further assumption that the phagocyte depletion after intravaginal instillation is limited to the vaginal tissue.
Iijima, et. al. sought to evaluate the contribution of dendritic cells in stimulating memory CD4 T cells to secrete IFN-γ as a defense against vaginal re-challenge by HSV-2 in HSV-2-immune mice. In order to deplete the local phagocyte population, 10 μl of clodronate liposomes was instilled intravaginally (ivag) and 250 μl of clodronate liposomes was injected i.v. on days -4 and -1 prior to intravaginal challenge by HSV-2 on day 0. ~80% of the macrophages and dendritic cells were depleted from the vagina (FACS analysis of vaginal secretions).

Original publication: 

1) N. Iijima, M.M. Linehan, M. Zamora, D. Butkus, R. Dunn, M.R. Kehry, T.M. Laufer, A. Iwasaki, Dendritic cells and B cells maximize mucosal
Th1 memory response to herpes simplex virus, Journal of Experimental Medicine, 205 (2008) 3041–3052.

Figure 1- Extracted data about dosage and liposome composition (one reference)