Pharmacy and Pharmaceutical Sciences Commons^™

Characterization Of The Hepatotoxicity Of Rifampicin And Isoniazid, Christopher T. Brewer

Theses and Dissertations (ETD)

In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase of protoporphyrin ix (PPIX), the penultimate heme precursor. Excess PPIX is believed to bind to bile acids, precipitate in bile canaliculi, and form bile plugs leading to cholestasis fol owed by liver injury. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to up-regulate Alas1 but down-regulate Fech protein levels in mice; however the mechanism of isoniazid mediated heme synthesis …

Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley

Theses and Dissertations (ETD)

Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - …

Rheological Studies Of Injectable Thermoresponsive Biodegradable Hydrogels And Porcine Ocular Tissues, Chandana Reddy Damera

Theses and Dissertations (ETD)

This research has evaluated the rheological properties of two types of materials which include (i) semi-synthetic polymer-based injectable hydrogels [P(NIPAAm-co-DEX-Lactate HEMA) and P(NIPAAm-co-HA-AEMA)], and (ii) biological tissues (porcine ocular tissues).

A series of thermoresponsive and biodegradable in situ hydrogel based on N-isopropyacrylamide (NIPAAm) monomer and hydrolytically degradable oligolactate Dextran-lactate-HEMA or Hyaluronic acid (HA)-AEMA macromer were investigated as encapsulation matrices (scaffolds) for DPSCs/ADSCs and assess their applicability in dental/retinal tissue engineering. The rheological properties of the hydrogels were strongly dependent on the reaction conditions and composition of the hydrogels. Both the hydrogels exhibited linear viscoelasticity, and the values of storage moludus …

Discovery Of Novel Tubulin Inhibitors And Selective Survivin Inhibitors For Advanced Melanoma And Total Synthesis Of Bioactive 20s-Hydroxyvitamin D3, Qinghui Wang

Theses and Dissertations (ETD)

According to the statistics from American Cancer Society, the 5-year survival rate for patients with advanced melanoma is as low as 5%. Treatment of advanced melanoma, therefore, represents an unmet medical need. In this dissertation, I will show the effort to develop new generations of bioavailable tubulin inhibitors targeting the colchicine binding site and selective small-molecule survivin inhibitors for treating advanced melanoma. Extensive structure-activity relationship (SAR) studies of lead molecules ABI-231 and UC-112 have been performed.

Chapter 1 will introduce the current situation of advanced or metastatic melanoma, its clinical drug treatments, as well as problems in current drug treatments. …

Translational Pharmacokinetic-Pharmacodynamic Modeling And Simulation In The Development Of Spectinamides, A Novel Class Of Anti-Tuberculosis Agents, Chetan Rathi

Theses and Dissertations (ETD)

New chemotherapeutic agents are urgently needed to control the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of tuberculosis, which still remains an important public health challenge globally. Recently, spectinamides have emerged as a novel class of anti-tuberculosis agents that overcomethe native drug efflux. Spectinamides bind to the 30S bacterial ribosomal subunit which interferes with ribosomal translocation, and ultimately results in inhibition of protein synthesis. They have potent in vitro activity against drug resistant Mycobacterium tuberculosis (Mtb), and also demonstrated sustained efficacy in (Mtb)-infected mouse models. Pharmacokinetic (PK)/ pharmacodynamic (PD) analyses play a critical role in identifying …

Design, Synthesis, And Evaluation Of Novel Positron Emission Tomography Radiotracers, Christopher Philip Surdock

Theses and Dissertations (ETD)

Neuroblastoma (NB) is the most common extracranial tumor in patients under 1 year of age and it constitutes about 8-10% of all childhood cancer. It originates from neural crest cells that normally differentiate to form the sympathetic ganglia, adrenal medulla and other paraspinal sites where sympathetic nervous system tissue is present. Even with an extensive treatment regimen that typically includes surgery, chemotherapy, total body irradiation and autologous stem cell transplantation, the 5-year event-free survival is <50% for high risk patients, and there are numerous long-term side effects associated with treatment. This body of work investigated two projects for improving patient outcomes through the development of positron emission tomography (PET) radiotracers that could be used for therapy planning. The goal of the first project was to design, synthesize, and evaluate PET radiotracers that could measure the enzymatic activation of Irinotecan (CPT-11), a potent chemotherapeutic used in the treatment of colon cancer and several pediatric solid tumors. CPT-11 itself is a prodrug which is converted in vivo to SN-38, via metabolism by carboxylesterase (CE) enzymes. St. Jude Children’s Research Hospital researchers have designed a two-pronged protocol of tumor-targeted CPT-11 chemotherapy combining the complementary approaches of a) specific modulation of human CE in normal tissues to improve drug delivery, and b) tumor-targeted activation of prodrug using neural progenitor cells (NPC) transfected with a mutant human CE cDNA. The tumor-selective trafficking of NPC allows over-expression of CE within the tumor. This prodrug/activating enzyme therapeutic approach has shown extremely encouraging preclinical results in the treatment of NB (90% 1-year survival in mice). However, successful translation of this novel therapeutic approach into general clinical practice requires a better understanding of progenitor cell trafficking, duration and intensity of enzymatic activity and the ultimate biological fate of the therapeutic construct. Toward this end, PET radiotracers were developed based on extensive structure-activity relationship (SAR) studies of CE binding. The goal of the second project was to design, synthesize, and evaluate PET radiotracers that could identify the presence of the tropomyosin receptor kinase B (TrkB). TrkB is not normally found in sympathetic nervous tissue, which is the tissue NB develops from, and thus is a potential target for imaging and therapy. The presence of TrkB and its neurotrophin, brain derived neurotrophic factor (BDNF), have been reported to protect neuroblastoma tumor cells from chemotherapy-induced apoptosis via a phosphatidylinositol 3’-kinase pathway. Radiotracers were synthesized and evaluated for their ability to identify TrkB both in vitro and in vivo. PET radiosynthetic procedures were optimized to synthesize novel radiotracers for imaging targets that could help clinicians monitor therapy or identify markers that would aid in therapy planning for NB patients. The method development could be applied to future compounds that show improved chemical characteristics for synthesis and selectivity.

Biodegradable Polymeric Biomaterials In Different Forms For Long-Acting Contraception And Drug Delivery To The Eye And Brain, Dileep Reddy Janagam

Theses and Dissertations (ETD)

Efficacy of many of the new and existing therapeutics is often hampered by the lack of an effective and compliant method of delivery. Typically, drugs have poor water solubility, short half-lives, and low permeability across the biological membranes. The result is low bioavailability of the drugs at the target site and can cause toxicity and side effects at high doses. Often the conventional dosage forms fail to overcome these limitations. In the recent decades, biodegradable polymeric drug delivery systems have emerged as promising candidates to solve the challenges of poor solubility, low permeability and sustained release owing to the advantages …

Cannabinoid Receptor 2 (Cb2) Ligands Downregulate Pro-Inflammatory Markers In Stimulated Primary Human Periodontal Ligament Fibroblasts (Hpdlfs), Ammaar Hasan Abidi

Theses and Dissertations (ETD)

There are approximately 743 million individuals suffering from chronic periodontitis (PD) making it the sixth most prevalent condition worldwide. The affected adult population in the U.S. are nearly 64.7 million and the healthcare costs exceeds $14 billion. Recently, host response to pathogenic infection has been seen critical to the progression of PD and exhibit increase in various inflammatory markers. Marijuana is well known for its recreational usage and is a risk factor for periodontal disease, which is seen as a concern in society for its negative health consequences. However, many medical conditions can benefit from the pharmacological effects of cannabinoids. …

Age-Associated Expression Patterns Of Oatp 1b1 And Oatp 1b3 And Their Effect On The Disposition Of Fexofenadine, Margaret Mary Thomson

Theses and Dissertations (ETD)

As part of the drug disposition process (absorption, distribution, metabolism, excretion), an often overlooked aspect is transport. In order for drugs to be metabolized and excreted from the body they go through the liver or other drug removal organs. For drugs that are polar or are large they must rely upon transport mechanisms to transport them across the biomembranes of the drug removal organs. OATP1B1 and OATP1B3 are transporters on the sinusoidal membrane of the liver which work in concert with the drug metabolizing enzymes as part of the drug removal process. It is known that the development of each …

Discovery Of Natural Product-Based Antimycobacterial Agents Effective Against Non-Replicating Bacilli, Shajila Siricilla

Theses and Dissertations (ETD)

New antimycobacterial molecules that kill non-replicating Mycobacterium tuberculosis (Mtb) were identified by screening libraries of synthetic natural products. De novo screening of a 400-membered library of aurachin RE analogs resulted in discovery of UT-317 ((R)-20). UT-317 is a selective vitamin K2 biosynthesis (MenA) inhibitor that killed replicating and non-replicating Mtb at 2.31 μg/mL (MIC) and 0.85 μg/mL, respectively. A 50-membered library of capuramycin analogs was evaluated in their enzymatic inhibitory activities against translocase I (MraY/MurX) and prenyl-phosphate-GlcNAc-1-phosphate transferase (WecA). UT-01320 (45) is identified as a selective WecA inhibitor that kills both replicating and non-replicating Mtb at 1.50 μg/mL (MIC) and …

Synthesis Of 20s-Hydroxyvitamin D3 Analogs And Their 1Α-Hydroxyl Derivatives As Potent Anti-Inflammatory Agents, Zongtao Lin

Theses and Dissertations (ETD)

Rheumatoid arthritis (RA) is one of the autoimmune diseases, and is affecting 2.5 million Americans in total. Among the treatment options of RA, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the only steroidal drug used clinically for anti-inflammatory and immune diseases. However, long-term use of 1,25(OH)2D3 (625 µg/day) in human would result in hypercalcemia (toxicity), and 1,25(OH)2D3 has substantial hypercalcemic effects (toxicity) in mice at a dose as low as only 2 µg/kg. Fortunately, during the investigation of novel metabolic pathway of vitamin D3 by cytochrome P450 enzymes, we found 20S-hydroxyvitamin D3 [20S(OH)D3] as a good lead compound. 20S(OH)D3 suppressed disease symptoms at …

The Development Of Methods To Account For Physiologic Dynamic Changes And Their Effects On The Pharmacokinetics Of Therapeutic Monoclonal Antibodies And Other Therapeutics, Josiah Thomas Ryman

Theses and Dissertations (ETD)

Physiologic changes in the body can drastically affect the clearance of a medication, and therefore increase the variability in exposure to the medication. Physiologic changes that can have a profound effect on the exposure of a medication can stem from changes CYP enzymes, transport proteins, binding protein expression, organ function, immune reactivity, and health status to name a few; with the focus of this dissertation on the dynamic changes in the ontogeny of MRP2 (an apical liver transport protein) and the dynamic changes caused by an immune response to a therapeutic monoclonal antibody (mAb). Several approaches can be used to …

Biophysical And Biochemical Screening Approaches For Antimicrobial Drug Discovery Targeting S. Aureus Clpp, Aman Preet Singh

Theses and Dissertations (ETD)

The discovery of antibacterial drugs has been among most significant achievements of mankind in saving millions of lives across the planet from infectious diseases. With rise in resistance to almost all existing chemotypes, the design of next generation novel antibiotics has become much more challenging and difficult. The early 21st century witnessed the advancement of multiple novel chemotypes during golden age of antibiotics however the pace of antibiotic drug discovery has slowed down tremendously, contributing to life threatening antimicrobial discovery void since 1980’s. Therefore the need to develop novel antibiotics with unique mechanism of action to leverage against multi drug …

Regulation Of Cancer Metastasis By Protein Kinase D1: A Global Regulatory Cascade, Aditya Ganju

Theses and Dissertations (ETD)

Protein Kinase D1 (PKD1) is a serine threonine kinase which is downregulated in Prostate, Breast and Colon Cancer. It functions as a tumor suppressor in different cancer cells. Downregulation of PKD1 is known to be associated with aggressiveness of the cancer. PKD1 is known to regulate many key oncogenic signaling pathways such as E-cadherin, β-catenin and Androgen Receptor signaling pathways. Aberrant expression of these oncogenic pathways leads to transformation of cells from normal to malignant phenotype, thereby leading to increased proliferation, growth and metastasis to distant organs of these cancer cells. Literature evidence also points to the fact that E-cadherin …

Repeated Zolpidem Treatment Effects On Sedative Tolerance, Withdrawal, Mrna Levels, And Protein Expression, Brittany T. Wright

Theses and Dissertations (ETD)

Zolpidem and benzodiazepines (BZs) potentiate the inhibitory action of gamma-Aminobutyric acid (GABA) by allosterically binding to GABAA receptors (GABAAR). Prolonged use of GABAAR positive allosteric modulators (PAM) can lead to behavioral tolerance, the diminished response to the same drug dose with repeated use, and withdrawal, a group of symptoms that occur due to abrupt end of drug treatment. Zolpidem is a short-acting, non-BZ GABAAR PAM whose potential for tolerance and withdrawal is unclear. Zolpidem demonstrates sedative efficacy similar to BZs and has become a main treatment of insomnia in lieu of BZs. Zolpidem replaced BZs due to lower incidences of …

Discoveries Of Targets And Novel Agents For The Treatment Of Ischemic Retinopathy And Neovascular Disease, Jordan Javad Toutounchian

Theses and Dissertations (ETD)

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are among the most common causes of blindness in adults. Vision loss can occur during the advanced stages of DR and AMD as a consequence of unregulated and dysfunctional growth of new blood vessels, or neovascularization (NV) in the retina or choroid. NV can also be triggered by numerous other ocular insults and diseases including radiation retinopathy (RR) and retinal vein occlusion. These latter cases are generally less common but, like DR and AMD, they are characterized by an initial injury, chronic inflammation, and ischemia which perpetuates episodes of retinal neovascularization (RNV). …

Antibiotic Drug Discovery With An Eye Towards Overcoming Drug Resistance, Daniel Towner Hoagland

Theses and Dissertations (ETD)

As a species, humans have become ever reliant on the use of antibiotics to facilitate our everyday lives. The widespread emergence of resistance to currently used antibiotics is commonly attributed to an over use in our society. Such resistance, coupled with a lack of innovation and production of novel antibiotic drugs, threatens to return humanity to an era similar to one before the discovery of the first antibiotics. The need to find new agents to be used in this fight is paramount, as well as learning from our recent failures to produce such compounds. This document will highlight my efforts …

Hit Identification For Pkcζ Inhibitors: Structure-Based Optimization, Virtual Screening, And Biological Evaluation, Xiaoxin Wu

Theses and Dissertations (ETD)

Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure …

Development And Evaluation Of Amphotericin B Loaded Iron Oxide Nanoparticles For Targeted Drug Delivery To Systemic Fungal Infections, Pavan Balabathula

Theses and Dissertations (ETD)

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and ζ-potential using dynamic light scattering (DLS) technique, morphology with …

Development Of Oral Vaccines Against Lyme Disease, Rita Raquel Dos Anjos De Carvalho E Melo

Theses and Dissertations (ETD)

Lyme Disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. If left untreated, it can lead to permanent damage to the nervous and musculoskeletal systems. In some cases, patients that receive the recommended antibiotic therapy develop a debilitating health condition associated with substantial health care costs. Despite current preventive measures, the incidence and the geographic distribution of Lyme Disease continues to increase. Recent estimates from CDC suggest that the true number of cases of Lyme Disease in the US is approximately 300,000 per year. Yet, there is currently no vaccine …

Optimization Of Lead Spectinamide Compounds As Novel Anti-Tuberculosis Agents With A Pharmacometric Approach, Ashit Rasendu Trivedi

Theses and Dissertations (ETD)

In an effort to combat the global Tuberculosis pandemic, Dr.Richard E. Lee and his group at St.Jude Children’s Research Hospital designed a novel series of anti-tuberculosis agents, spectinamides – semi-synthetic analogs of spectinomycin. Spectinamides are a potent inhibitor of mycobacterial ribosomes and overcome efflux mediated drug resistance in M. tb. Spectinamides have shown an excellent in vitro activity, which makes them well suited for further lead optimization and preclinical development. We hypothesized that through pharmacokinetic (PK) and pharmacodynamics (PD) model-based dosing optimization studies, we could strategically guide the selection and refinement of more potent and effective anti-TB spectinamides. Biopharmaceutical in …

Discovery Of Novel Tubulin Polymerization Inhibitors And Survivin Inhibitors As Potential Anticancer Agents, Min Xiao

Theses and Dissertations (ETD)

Melanoma is the most dangerous form of skin cancer and accounts for the majority of skin cancer death. Although considerable advances have been made in melanoma treatment in recent years, there are many problems associated with current therapies. Drug resistance to targeted therapies is almost inevitable after short term treatment. Immunotherapies generally have low response rate and the effects vary among patients. Therefore, the need to develop new and more effective treatment for melanoma is high.

The work presented here focuses on discovery of novel anticancer agents for melanoma by targeting two important cancer targets: tubulin and survivin. Microtubules play …

Challenges In The Pharmacokinetics Of Therapeutic Proteins, Wararat Limothai

Theses and Dissertations (ETD)

Due to the complex structure and complicated disposition pattern of therapeutic macromolecules, their pharmacokinetic interpretation has many challenges. Two of these challenges were investigated in this dissertation: 1) the error of classical bioavailability assessment observed during subcutaneous (SC) administration of therapeutic macromolecules that undergo target-mediated drug disposition (TMDD) and 2) the ontogeny of the neonatal Fc receptor (FcRn) expression along with its effect on the pharmacokinetics of monoclonal antibodies (mAbs) during development.

TMDD often well describes the pharmacokinetics of therapeutic proteins that have high specificity and affinity of binding to their target receptors. The target receptors can be saturated by …

Overcoming Acquired Resistance To Braf Inhibitors By Novel Synergistic Drug Combination And Discovery Of Novel Smac Mimetics As Selective Survivin Inhibitors, Jin Wang

Theses and Dissertations (ETD)

The first part (Chapter 1 and 2) of this dissertation presents a novel combination study of melanoma therapy. Acquired clinical resistance to vemurafenib, a selective BRAFV600E inhibitor, arises frequently after short term chemotherapy. Since the inhibitions of targets in the RAFMEK-ERK pathway result in G0/G1 cell cycle arrest, vemurafenib-resistant cancer cells are expected to escape this cell cycle arrest and progress to subsequent G2/M phase. We hypothesized that a combined therapy using vemurafenib with a G2/M phase blocking agent will trap resistant cells and overcome vemurafenib resistance. To test this hypothesis, we first determined the combination index (CI) values of …

The Value Of Online Medication Rating Systems To Older Adults And Their Association With Self-Reported Outcomes, Yazed Sulaiman Alruthia

Theses and Dissertations (ETD)

The Internet is a powerful and very popular vehicle for distributing judgment-free health information to patients. Multiple studies have examined the role of online health information as well as physician-rating websites in health care. Studies have examined the value of online drug information for patients and the value of the online drug information for patients. However, no study has examined the usefulness or value of online medication rating websites in facilitating physician-patient communication or participant-reported outcomes. In this study, the value of online medication rating websites to older adults in facilitating communication with their physicians using a newly developed tool …

Design, Development And Evaluation Of Erlotinib-Loaded Hybrid Nanoparticles For Targeted Drug Delivery To Nonsmall Cell Lung Cancer, Bivash Mandal

Theses and Dissertations (ETD)

The objective of this work was to design, develop and evaluate erlotinib-loaded coreshell type lipid albumin hybrid nanoparticles (CSLAHNPs) for targeted drug delivery to nonsmall cell lung cancer (NSCLC). Erlotinib (ETB) is a highly selective, potent and reversible inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR) which is overexpressed (50-90%) in NSCLC. ETB is marketed as film coated tablets for oral delivery. However, poor survival rate along with life-threatening adverse effects were reported from oral administration. Nanoparticulate delivery system of ETB might be advantageous to target the tumor cells, thereby increasing therapeutic efficacy and reducing off-targeting toxicities of ETB …

Design, Development, Characterization And Testing Of Cd22 Targeted Long Circulating Liposomal Drug Delivery Systems For B Cell Malignancies, Nivesh Kumar Mittal

Theses and Dissertations (ETD)

Hematological malignances of the B cells affect almost 130,000 people in the United States every year of which approximately 44,000 lose their lives. Therapies for B cell malignancies such as doxorubicin, have limitations due to dose related adverse effects such as neutropenia and cardiomyopathy. AD 198 is a novel PKC-delta activating agent that has cytotoxic superiority over doxorubicin by being able to circumvent resistance mechanisms developed by the cancer cells towards doxorubicin and being cadioprotective from the damage caused to cardiomyocytes by doxorubicin. Targeted delivery of AD 198 is crucial to moderate the non-specific interactions of the chemotherapeutic agent with …

Functional Activity And Switching Of Novel Cannabinergic Ligands, Bret Alan Koertge

Theses and Dissertations (ETD)

Pursuant to the discovery of the cannabinoid receptors, research in this field has grown exponentially over the last 2 decades. With their utility in various disease states such as heart disease, cancer, stroke, neurodegenerative and inflammation, cannabinoids stand poised to become a great therapeutic agent. This research seeks to better understand the functional mechanism of cannabinoids, in the hopes of ascertaining which molecular attributes confer desirable selectivity and functional activity.

Looking first at classical benzchromene core analogues, we have shown that presence of an aromatic substitution at C-1' imparts a CB1 agonist, CB2 antagonist. This is a unique mechanism and …

Computer-Aided Drug Design And Discovery, Screening And Synthesis Of Small Molecule Inhibitors Of Nucleoside Transporters, Hilaire Colleen Playa

Theses and Dissertations (ETD)

Using prior biological data, pharmacophore models were made for hCNT1, hCNT3, hENT1, and hENT4. The hCNT3 and hCNT1 pharmacophore were used to select compounds for biological testing. The NBMPR analogue and dipyridamole analogue hENT1 pharmacophores were compared to each other and to a combined pharmacophore for hENT1. The dipyridamole analogue pharmacophore better predicted non-nucleoside small molecule inhibitors, and as such appears to be the better tool for aiding in the design of new small molecule inhibitors. The hCNT3 pharmacophore failed to select active compounds and as such must be redesigned. The hCNT1 pharmacophore succeeded in identifying two moderately active compounds …

Development Of A Novel Vaccine Adjuvant System Utilizing An In Situ Implant System To Modified Release, Qiuye Zhang

Theses and Dissertations (ETD)

Pulsatile release formulations for single dose vaccines have been studied for many years because of the advantages that they may provide to vaccine administration with a single dose instead of prime and booster shots.

The aim of this work is to develop novel formulations based on an In Situ Implant (ISI) systems to provide a modified vaccine release and altered immune response, which could act as a booster administration. This type of system was selected because ISI systems are used for long acting administration of various drugs and ease of administration. A typical ISI system is comprised of hydrophilic organic …