title: Evaluation of microparticulate ovarian cancer vaccine via transdermal route of delivery.
abstract: Ovarian cancer is the fifth most commonly occurring malignancy in women, with the highest mortality rate among all the gynecological tumors. Microparticulate vaccine can serve as an immunotherapeutic approach with a promising antigenic delivery system without a need for conventional adjuvants. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared by spray drying. Further, the effect of interleukins (ILs) such as IL-2 and IL-12 was evaluated in a separate study group by administering them with vaccine particles to enhance the immune response. The vaccine microparticles were administered to C57BL/6 female mice via transdermal alone and in combination with the oral route. The transdermal vaccine was delivered using a metallic microneedle device, AdminPen™. Orally administered microparticles also included an M-cell targeting ligand, Aleuria aurantia lectin, to enhance the targeted uptake from microfold cells (M-cells) in Peyer's patches of small intestine. In case of combination of routes, mice were given 5 transdermal doses and 5 oral doses administered alternatively, beginning with transdermal dose. At the end of vaccination, mice were challenged with live tumor cells. Vaccine alone resulted in around 1.5 times tumor suppression in case of transdermal and combination of routes at the end of 15th week when compared to controls. Inclusion of interleukins resulted in 3 times tumor suppression when administered with transdermal vaccine and around 9 times tumor suppression for the combination route of delivery in comparison to controls. These results were further potentiated by serum IgG, IgG1 and IgG2a titers. Moreover, CD8+ T-cell, CD4+ T-cell and NK (natural killer) cell populations in splenocytes were elevated in case of vaccinated mice. Thus, vaccine microparticles could trigger humoral as well as cellular immune response when administered transdermally and via combination of route of delivery. However overall, vaccine administered with interleukins, via combination of route, was found to be the most efficacious to suppress the tumor growth and lead to a protective immune response.
authors.affiliation: Akorn Pharmaceuticals, Research and Development, 50 Lakeview Parkway, Suite 112, Vernon Hills, IL 60060, USA. Electronic address: suprita25@gmail.com.
authors.forename: Suprita A
authors.initials: SA
authors.lastname: Tawde
authors.affiliation: Department of Pharmaceutical Sciences, St. John Fisher College, 3690 East Ave, Rochester, NY 14618, USA.
authors.forename: Lipika
authors.initials: L
authors.lastname: Chablani
authors.affiliation: Wil Research Laboratories LLC, 1407 George Rd, Ashland, OH 44805, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Akalkotkar
authors.affiliation: Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Sciences, Mercer University College of Pharmacy and Health Sciences, 3001 Mercer University Drive, Atlanta, GA 30341, USA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: D'Souza
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D018664:Interleukin-12 / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D037102:Lectins / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007376:Interleukin-2; D037102:Lectins; C064549:lectin, Aleuria aurantia; D018664:Interleukin-12
keywords: Microparticles; Ovarian cancer; Spray drying; Transdermal; Vaccine