• Formulation and Evaluation of Microparticulate System for the Development of Pneumonia and Influenza Vaccines

      Nagaraja Shastri, Prathap; College of Pharmacy
      In recent years vaccine research has gained a tremendous interest from both industries as well from the academic sectors. There are number of vaccines available in the market and still there is a scope of improvement in most of the marketed vaccines. The antigens used in vaccination are in general large molecules, either protein or polysaccharide based. These antigens can lead to specific antibodies that will protect our body from the infection. Some of the antigens are stable, however majority of them are instable and sensitive resulting in problems during formulation, storage. Formulation of protein or polysaccharide has always been a challenge for scientists due to several characteristics of the antigen and the dosage from itself. Microparticle is on the the dosage forms that have shown promising results in several vaccine studies in the past. In this study we have evaluated microparticle formulations for two infectious diseases namely, Pneumonia and Influenza. Both these are respiratory infections and the vaccinations against these are highly recommended by the Center for Disease Control. In particularly for Influenza the vaccination is recommended every year. In this research we have used two novel approaches to formulate these antigens using microparticles. The pneumococcal polysaccharide antigens are usually less immunogenic in nature and hence to potentiate their immune response the antigens were formulated in a cross linked albumin matrix. In case of Influenza vaccines, we have attempted to vaccinate via oral route of administration after formulating inactivated form of influenza virus in an enteric coated microparticle formulation. Upon formulation both theses vaccines were characterized for their physical properties such as particle size, zeta potential and also the bioactivity of these antigens in microparticles were measured using antigen specific bio assays, Further invivo studies were carried out in mice to evaluate the adaptive immune responce elicited by microparticle based vaccines. The results have been promising with increase in antibody titers for vaccine formulations and also better protection was observed in case of Influenza vaccine, Overall these promising results further emphasize the use of microparticles as a tool to deliver vaccine antigens effectively.
    • 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.
    • Formulation Design and Development of Theranostic Nanoparticles for Tumor Targeted Drug Delivery

      Kolluru, Lakshmi Prasanna; College of Pharmacy
      Cancer is among the leading cause of death in the world, accounting for one in every four deaths in United States. Researchers from academia and industry are working on discovering new drug targets, developing better drug products and enhancing efficacy of drug delivery systems. In spite of the advancements, drug delivery still remains a challenge in the management of cancer. Currently, Chemotherapy (mostly in combination with radiation) is a major therapeutic approach for the treatment of cancer. However several chemotherapeutic drugs lack the ability to differentiate between normal and tumor tissues and suffer from drawbacks such as dose limiting toxicity, low specificity and emergence of multidrug resistance. Major concerns associated with current anti-cancer agents which are gaining wide importance include rapid elimination from kidney and non-specific biodistribution. In addition, the rapid clearance of the drug from the body might require administration of larger doses which can cause toxic effects. One approach to reduce the systemic toxicity and enhance the efficacy of the drugs us to administer through selective drug delivery carriers. Polymeric nanoparticles offer promise for targeted drug delivery as they have the potential for passive targeting of drugs by Enhanced Permeable and Retention (EPR) effect, controlled/sustained release of drug, reduced clearance and ability for surface fuctionalization with tumor targeting ligands. In this studym we have successfully fabricated polymeric nanoparticles for the delivery of diagnostic and therapeutic agents using Bovine Serum Albumin (BSA) polymeric nanoparticles. Near Infrared dye, Indocyanine green and anti-cancer drug, Doxorubicin are used as model diagnostic and therapeutic agents respectively. Folic acid and cyclic RGD are used as tumor targeting ligands to target tumor microenvironment and tumor cells. This project focuses on the preformulation, formulation development, in vitro characterization and in vivo evaluation of the drug-dye loaded nanoparticles and evaluation of the active targeting potential is proposed. Spray drying and Nanoprecipitation techniques are evaluated and nanoprecipotation technique is used in final preparation. Nanoparticle suspension was then subjected to lyophilization. The formulation is further extensively characterized in vitro by Dynamic light scattering (DLS), Release Studies, Differential SCanning Calorimetry (DSC) and MTS Cytotoxicity Assey. In addition, the formulation is also evaluated in vivo for its tumor targeting potential by monitoring the biodistribution of entrapped near infrared dye using whole body non-invasive imaging technique. Results of our work demonstrated that diagnostic and therapeutic agents can be effectively delivered in a single delivery system. Our work further emphasizes that nanoparticle based system can enhance localization of diagnostic (or therapeutic agents) into the tumor, thereby contributing to reduces side effects and enhanced efficacy.
    • Formulation Develoment and Characaterization of Polycaprolacton/Pluronic F108 NanoParticles for Targeted Breast Cancer Therapy

      Chandran, Thripthy; College of Pharmacy
      Breast Cancer ranks first among cancer deaths for women after malignant lung cancer in the United States. Despite the major advancements in the treatment of breast cancer, it still poses a major challenge. While chemotherapeutic intervention remains the major treatment approach fr cancer, they suffer from several drawbacks including dose limiting toxicity, non-specific biodistribution, and emergence of resistance in solid tumors, thus posing a risk of relapse. Furthermore, the excipients used for the administration of the anticancer agents also cause several undesirable systemic effects such as nephrotoxicity, neurotoxicity, and hypersensitivity reactions when given intravenously. Biodegradable polymeric nanoparticles have emerged as promising targeted drug delivery systems for the delivery of anticancer drug owing to their size characteristics., their ability to passively accumulate by Enhanced Permeability and Retention (EPR) effect in the tumors, ability to protect the active ingredients from degradation, providing a controlled/sustained release of the active ingredients and b tunable for the attachment of active ligands according to a patient's tumor profile and thus provide a personalized therapy. In this study, we designed polymeric nanoparticles for the delivery of anticancer agent docetaxel using poly-e-caprolactone (PCL), which forms the core of the the nanopartilces. Pluronic polymer F108 is used as an emulsifying agent/stabilizer for the PCL nanoparticles, providing a hydrophilic PEG coating thus stealth properties to the nanoparticles. The passive targeting ability of the nanoparticles is evaluated using a near infrared carbocyanine dye (Dir). Trastuzmab is used as an active targeting ligand to target the HER-2 receptors present on the human breast cancer BT-474 cells. Thus, this project focuses on the formulation development, in vitro characterization of docetaxel loaded nanoparticles and finally the characterization of trastuzumab conjugated nanoparticles.
    • Freirean Pedagogical Love In P-12 Education: A Theory-to-practice Investigation

      Smith-Campbell, Charmaine Joan
      ABSTRACT This theory-to-practice qualitative narrative study uses Freire’s (2005, 2011) ideas of pedagogical love to create a Freirean critical social justice approach (FCSJEA). This approach serves as a framework for comparisons, analysis, and discussions of emic themes from the study’s eight participants’ narratives, to etic elements of the study’s Freirean model. The purpose of these comparisons are to determine whether or not, and to what extent, parallels, areas of conversion, or areas of divergence exist between both as well as for identifying possibilities for theory-to-practice applications for this model in P-12 curriculum development, instruction, and learning in contemporary U.S. settings. The study utilizes a methodological bricolage that blends Stake’s (1995) qualitative instrumental design with the qualitative narrative approach found in Clandinin and Connolly (2000) and others. A criterion-based purposeful sampling determined selection of included participants. Findings indicate that the Freirean model offers a useful theory-to-practice approach for transformative P-12 education. There are two sets of recommendations. The first involves a need for scholarly theory-to-practice research similar to this study. This should include diverse participant pools and multiple voices including students, parents and caregivers, teachers, policymakers, school leaders, as well as all other interested parties. The second set of recommendations calls for teachers, all educators, curriculum workers, and education policy makers to utilize Freire’s language of humanization education as starting points for transformative P-12 educational actions. These recommendations call on each of us to become morphogenetic change agents as described by Freire, this study, and Archer’s (1995, 2013a, 2013b, 2016) change process. These are the possibilities hoped for by Freire and the faith upon which this study stands. Keywords: Freirean pedagogical love, Dewey, morphogenesis, postmodern theory, Freirean critical social justice educational approach (FCSJEA), dehumanization/ humanization, transformative education, equity, justice, bricolage, instrumental-narrative design, pre-kindergarten to 12 grades (P-12), emic themes and elements, etic themes and elements.
    • From Disorientation To Reorientation: Introducing Theological Worlds To Enhance The Sense Of Spiritual Support Among Selected Students At Landmark Christian School

      Hamaker, Trevor Tyson
      Adolescence is often a time of disruption in teenager’s lives. For many Christian teenagers, this disruption affects their faith, creating a period of disorientation. Previously, these young people assumed the faith of their parents, but adolescence opens the door to rethink and reassess those commitments. Unless they sense a personal, vital connection to their faith, they will likely move away from it in the future. This study introduced a group of twelfth-grade students at Landmark Christian School to W. Paul Jones’ concept of Theological Worlds. The researcher expected to learn what difference it makes for Christian adolescents who are experiencing a time of transition in their religious lives to consider which Theological Worlds they and others inhabit. The students were selected based upon their designation as “Transitional�? by the Spiritual Experience Index – Revised (SEI-R). The project consisted of six weekly meetings with the group of thirteen participants. During each forty-five-minute meeting, different aspects of each Theological World were introduced through scripture, songs, and videos. Participants then recorded their reflections about what they had seen and heard. After finishing the six meetings, participants completed the SEI-R again to measure if any difference was made. Eleven out of the thirteen participants indicated an increased sense of support related to their faith. The average sense of support among the entire group of participants had risen by almost nine percent. Follow-up interviews with the participants confirmed the accuracy of the data and brought further clarity to the factors that contributed to the increased scores. Among those factors was the sense that they were not alone in the ways they experience and express their faith, as well as the focused attention that was given to the topic for the duration of the study. This thesis concludes by suggesting several ways that these findings can be applied both at and beyond Landmark Christian School to help adolescents move from disorientation to reorientation around the topic of faith.