• Development of Microencapsulated Formulations for Prostate Cancer Vaccine and Live Cells

      Akalkotkar, Archana; College of Pharmacy
      In the current trend, novel particle based platform technology has paved its way to various therapeutic benefits in our lives. In this study, we explored the way of harnessing this technology in order to formulate effective vaccines in the quest for mass immunization in a cost-effective manner. Here we propose a custom formulation of vaccines, which will render effects of sustained release, site specificity and cost-effective delivery of various antigens to enhance the immunity. We used the novel nano-micro technology based of Spray drying as a platform to deliver vaccines against Prostate cancer and encapsulated live cells. In this study, we formulated a whole cell lysate vaccine against prostate cancer via oral and transdermal route of administration. The formulation intended for oral adminstration was optimized for M-cell targeting, The formulation increased the immunogenicity of the vaccine by incorporating the antigen into an albumin matrix having a size of around 0.35-1.2 um that acted as a synthetic adjuvant. The animals were vaccinated with 1 prime and 4 booster doses administered every 14 days over 10 weeks duration, followed by challenge with live tumor cells which showed protection after oral vaccination. Unlike subcutaneous injections, administration-using microneedles is painless and in general can increase the permeability of many compounds ranging in size from small molecules to proteins and microparticles that do not normally penetrate the skin. The mice vaccinated via transdermal route showed promising results in delaying the tumor growth compared to the controls. The study was extrapolated in a therapeutic approach. This would mimic the real clinical scenario where the patient who was diagnosed with prostate cancer would come in the clinic for immunotherapy. The microparticle based delivery system showed protection in vaccinated group compared to the controls. This shows the microparticle based delivery system can be an useful tool for delivery as well as live cells in vivo.
    • Formulation and In Vivo Evaluation of Particulate Breast Cancer Vaccine

      Chablani, Lipika; College of Pharmacy
      Purpose: This research work concentrates on formulating two particulate breast cancer vaccines, which are further evaluated in vivo using two murine breast cancer models. As breast cancer continues to be the most fatal cancer among women throughout the world, there is an immediate need to develop a vaccine to combat it. Considering the potential of particulate delivery vehicles to impart robust systemic as well as mucosal immune response, they have been explored not only against infectious diseases but also against cancer. In this project we take advantage of these micron sized particulate delivery vehicles to target immune cells and to initiate immune response against breast cancer antigens, Also, these particles have been fabricated in such a manner that they can be administered via patient-compliant routes of administration including oral and intraepidermal delivery. Research methodology: We have explored various polymers to optimize two enteric protected particulate delivery systems with desired physical properties making them susceptible to particle uptake and there by leading to anticipated immune response. These particles have been evaluated carefully for their size, charge, surface morphology, release profiles, cyto-toxicity and particle uptake by various in vitro studies. Further the particle uptake of vaccines by the M (microfold) cells in the Peyer's patches of the small intestine when given orally is studied extensively along with characterization of microchannels created to deliver the microparticulate vaccine. Also, the vaccine efficacy was evaluated in vivo in female mice model using the two marine breast cancer cell lines which mimic the progression of breast cancer as seen in humans, The vaccine was administered via oral, intraepidermal and sub-cutaneous routes resulting in immune response against the breast cancer antigens used in the vaccine. Results and Conclusion: The vaccinated animal had sugnificantly smaller tumor volumes than the control animals, as seen after challenging the animal upon termination of treatment. Immune responses in all the animals were monitored to gauge the role of humoral and cellular immunity in generating protection by several in vitro and ex vivo studies. Promising results from these two prophylactic particulate breast cancer vaccine studies have advanced our laboratory to explore a therapeutic breast cancer vaccine. These particulate delivery systems possess the potential of entering the clinical trials and mimicking the real-time situation where patient's own tumor cells extracted after a surgery can serve as the source of antigens for an individualized particulate vaccine.
    • Overian Cancer Microparticulate Vaccines: Effect of Routes of Administration

      Tawde, Suprita Ashok; College of Pharmacy
      Ovarian cancer is the most lethal gynecological cancer in the U.S. First-line treatment for advanced cancer involves surgery followed by chemotherapy. However, cancer relapses within short periods of time even after treatment. Therefore, alternative approach of immunotherapy is being investigated. We studied vaccination with microparticles containing the ovarian cancer antigens can prevent/retard ovarian cancer growth. Oral and transdermal routes are attractive modes of immunization because of their ease of administration and patient compliance. In this project we explored microparticulate system to target immune cells and to initiate response against ovarian cancer antigens via oral, subcutaneous and transdermal delivery. We selected a murine cell line which correlates closely to human cell line in terms of antigen expression and tumor formulation. We prepared the antigenic lysate and characterized it for the presence of a known antigen. We loaded micro-particulate delivery systems with the lysate. These particles were formulated with desired physical properties suitable for particle uptake and for anticipated immune response. In the present study, we demonstrate the efficacy of vaccine formulations wuth was evaluated in vivo in mouse tumor model, using the murine ovarian cancer cell line as a solid tumor model via oral, transdermal, subcutaneous and via combination of oral and transdermal routes. The tumor volumes upon challenge with live tumor cells were monitored in vaccinated animals and control animals. Humoral and cellular immune response in all the animals were monitored to determine the immune mechanism initiated by the vaccine microparticles. Encouraging results from these prophylactic particulate overian cancer studies provided the basis to design therapeutic study to mimic the real-time scenario where patients with residual tumors after a surgery are the recipients of such vaccine therapy. Further, to elucidate the role of M-cells in particle uptake once administered orally, we induced M-cells in murine models and administered microparticles loaded with a model antigen with and without immune adjuvant. The immune response generated via these vaccine particles in mice models with induced M-cells was compared to control animals, to determine whether particles followed the M-cell pathway for their uptake in order to trigger immune cells.