Phenolic Acid Analogues as a Potential Drug Formulation for Inflammatory Diseases

Phenolic Acid Analogs as a Potential Drug Formulation for Inflammatory Diseases: We seek to establish the link between toll-like receptors (TLR) in the pathogenesis of inflammation and formulate a phenolic acid analog as a potential drug formulation for inflammatory diseases. We developed a stable drug-polymer complex of a phenolic acid using pH-sensitive polymers that will target inflammation. Various analogs were synthesized with nano-co-precipitation experimentation. Using a variety of polymers, solvents, and stabilizers the most effective combination for optimal delivery was determined. The particle size, drug loading, and dissolution profile under various pH are identified with various polymers. The formulated complex will be studied for biochemical, genetic changes in the human tissues in the class II environment. The physiological and pharmacological effects will be studied in live mice in an animal facility. These results will broaden the understanding and deduce the role that TLRs have in the causation of inflammation, and efficacy of the drug. In the long term, this may reveal TLRs as druggable targets and the phenolic acid polymer complexes as an inhibitor of the TLRs respectively. Specifically, this project aims to explore the effect of this stable drug-polymer complex on Inflammatory Bowel Disease, which affects 15% of American primary care patients. Currently, all pharmaceutical solutions pose negative side effects and the drug utilized in this complex will prospectively reduce these effects

Product Development from Apple, Grapes and Berries Food Waste: Market Research, Industry Analysis and Opportunity Assessment

This study focuses on the apples, berries, and grapes wastage produced by the population of North America and Europe. The research is aims to conduct in-depth comparison between these two regions based on volume and monetary value of fruit waste produced. The research was conducted by an inquiry based primary research with industry experts product development scientist and good waste management companies, and secondary research was conducted by collecting information from company’s websites, annual reports, white papers, and financial reports. This research open the reusability opportunity of fruit waste, optimize the food processing and manufacturing industry. The waste from apples, berries, and grapes are high in moisture and biologically active components (BACs) which make them ideal raw materials for the functional food product industry. The market research conducted in the study highlights the potential in the waste produced by apples, berries, and grapes during food processing and manufacturing through ingredient analysis and comparing it to the functional food ingredient requirements. The results of the market research and industry analysis will assist industries and researchers in finding and optimizing processes to reduce waste and maximize the extraction of fruits’ nutrients content. KEYWORDS: Food waste, Recycle, biologically active compounds, apple pomace, grape pomace, market valu

The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK Inhibitor and an Anti-Proliferative Agent: A Potential Role in Cancer Prevention

Flavonoids have emerged as promising compounds capable of preventing colorectal cancer (CRC) due to their anti-oxidant and anti-inflammatory properties. It is hypothesized that the metabolites of flavonoids are primarily responsible for the observed anti-cancer effects owing to the unstable nature of the parent compounds and their degradation by colonic microflora. In this study, we investigated the ability of one metabolite, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) to inhibit Cyclin Dependent Kinase (CDK) activity and cancer cell proliferation. Using in vitro kinase assays, we demonstrated that 2,4,6-THBA dose-dependently inhibited CDKs 1, 2 and 4 and in silico studies identified key amino acids involved in these interactions. Interestingly, no significant CDK inhibition was observed with the structurally related compounds 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) and phloroglucinol, suggesting that orientation of the functional groups and specific amino acid interactions may play a role in inhibition. We showed that cellular uptake of 2,4,6-THBA required the expression of functional SLC5A8, a monocarboxylic acid transporter. Consistent with this, in cells expressing functional SLC5A8, 2,4,6-THBA induced CDK inhibitory proteins p21Cip1 and p27Kip1 and inhibited cell proliferation. These findings, for the first time, suggest that the flavonoid metabolite 2,4,6-THBA may mediate its effects through a CDK- and SLC5A8-dependent pathway contributing to the prevention of CRC

Nutritional Transporter Mediated Drug Delivery for Cancer

Recent advancements in nanotechnology have unfolded novel opportunities in medicine, especially in targeted therapeutics and imaging for cancer. However, the majority of the existing nanotechnologies for cancer suffer from shortcomings such as (i) rapid elimination from the systemic circulation before reaching the cancer tissue. (ii) poor tumor accumulation, targeting, and penetration due to inadequate vasculature and extensive extracellular matrix in the tumor. Thus, overcoming these two limitations of nanotechnology is of considerable interests for cancer researchers. In this dissertation, we demonstrate the feasibility of glucose-modified nanoparticles (GLU-NPs) as an efficient cancer targeted-delivery system for enhancing the systemic circulation time and tumor accumulation. In chapter II, using a natural physiological interaction between glucose on the GLU-NPs and the surface glucose transporter GLUT1 on the RBCs, we have demonstrated the enhancement of systemic circulation time and thereby, improved tumor accumulation. GLU-NPs interaction with GLUT1 is non-covalent, reversible and importantly, established in-vivo. GLU-NPs enhanced the circulation time by hitchhiking on RBCs and reducing opsonization. In chapter III, we have demonstrated the ability of GLU-NPs to differentiate breast cancer versus noncancer cells based on the expression levels of GLUT1. GLUT1 is overexpressed in multiple cancer types, and the level of expression is correlated with the invasiveness of cancer. GLU-NPs were able to deliver significantly large amounts of encapsulated cargo to breast cancer cells potentially through caveolae-mediated endocytosis. The in-vivo tumor imaging results depict that the GLU-NPs highly accumulated into tumors compared to state-of-art technology PEGylation. In summary, we have demonstrated the ability of GLU-NPs as a smart drug delivery system for in-vivo enhancement of systemic circulation time and tumor accumulation, which will have applications beyond cancer therapy and imaging, such as sustained drug delivery and targeting to other organs

Formulation and Nanotechnology-Based Approaches for Solubility and Bioavailability Enhancement of Zerumbone

About 40–70% of drug molecules in the clinical development pipeline suffer from one of either low aqueous solubility, poor absorption, or extremely low bioavailability. Approximately 75% of the world population relies on traditional therapies and therefore there has been a growing interest in the utilization of natural compounds. Zerumbone is one such natural compound, classified as a sesquiterpenoid that is extracted from the essential volatile oils of rhizomes from Zingiber zerumbet. It possesses strong antitumor, antioxidant, antimicrobial, and anti-inflammatory activity. However, despite promising preclinical studies demonstrating the therapeutic utility of zerumbone, its clinical development has been limited due to its low aqueous solubility, poor absorption, or associated low bioavailability. Multiple reviews demonstrating the pharmacological effects of zerumbone for various diseases have been published. However, to our knowledge, no review demonstrates the various formulation strategies developed to overcome the biopharmaceutical challenges of zerumbone. The purpose of this review is to provide a comprehensive perspective on zerumbone as a molecule for formulation development. A section related to pharmacokinetics, toxicity, and patents of zerumbone is included. This review provides the importance of developing novel formulations of zerumbone to overcome its biopharmaceutical challenges thereby advance its potential in the treatment of various diseases

A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer

Background: Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of breast cancer with associated chemoresistance. The development of chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression of membrane proteins (transporters), epigenetic changes, and alteration of the cell signaling pathways/genes associated with the development of cancer stem cells (CSCs). Aim of review: Due to the diverse and heterogeneous nature of TNBC, therapeutic response to the existing modalities offers limited scope and thus results in reccurance after therapy. To establish landmark therapeutic efficacy, a number of novel therapeutic modalities have been proposed. In addition, reversal of the resistance that developed during treatment may be altered by employing appropriate therapeutic modalities. This review aims to discuss the plethora of investigations carried out, which will help readers understand and make an appropriate choice of therapy directed toward complete elimination of TNBC. Key scientific concepts of review: This manuscript addresses the major contributory factors from the tumor microenvironment that are responsible for the development of chemoresistance and poor prognosis. The associated cellular events and molecular mechanism-based therapeutic interventions have been explained in detail. Inhibition of ABC transporters, cell signaling pathways associated with CSCs, and epigenetic modification offers promising results in this regard. TNBC progression, invasion, metastasis and recurrence can also be inhibited by blocking multiple cell signaling pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics and generating reactive oxygen species (ROS)