• 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 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.