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Articles 1 - 9 of 9
Full-Text Articles in Medicine and Health Sciences
The Development Of Hyaluronan-Based Contract Agents For The Intraoperative Detection Of Pancreatic Tumors, Bowen Qi
Theses & Dissertations
Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. Tumor-specific intraoperative fluorescence imaging could improve staging and surgical resection, thereby improving prognosis. In the first study, hyaluronic acid derived NPs with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG accumulated significantly in an orthotopic pancreatic ductal adenocarcinoma model with safety profile both in vitro and in vivo. To maximize tumor signal, while minimizing signal in healthy pancreas and RES capture of macromolecules, in the next study, we describe the rational …
Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya
Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya
Theses & Dissertations
This work presents research using the naturally available non- sulfated carbohydrate glycosaminoglycan hyaluronic acid (HA) for the synthesis of different chemical derivatives of HA for evaluation of binding kinetics with CD44 and P- selectin proteins for applications in fluorescence image-guided surgery. Chemical derivatives of HA such as deacetylated HA (deHA), sulfated HA (sHA), and deacetylated and sulfated HA (s-deHA) were synthesized by modulating sulfating and deacetylating reagents to alter binding specificities to CD44. Modified HA derivatives and CD44 biophysical interactions were assessed by fluorescence polarization. In silico techniques were also used to determine binding using molecular docking and MM-PBSA approaches. …
Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub
Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub
Theses & Dissertations
Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …
Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann
Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann
Theses & Dissertations
RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …
Synthesis And Characterization Of Long-Acting Rilpivirine Prodrugs, James R. Hilaire
Synthesis And Characterization Of Long-Acting Rilpivirine Prodrugs, James R. Hilaire
Theses & Dissertations
Antiretroviral therapy (ART) requires lifelong daily dosing to suppress viral replication, restore or maintain immune function and improve quality of life. As an alternative, long-acting (LA) antiretrovirals (ARVs) aim to deliver therapeutic drug concentrations over an extended period, ultimately requiring monthly or even more extended dosing intervals. Specifically, the success of recent clinical trials examining LA cabotegravir and rilpivirine (CAB and RPV LA) highlight the advent of these novel HIV-1 therapeutics. Further optimization of LA dosage forms are required and rests upon improving dosing frequency, injection volumes and tissue distribution to viral compartments. To this end, we report the synthesis …
Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim
Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim
Theses & Dissertations
The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …
Development Of Macromolecular Prodrug Conjugates For The Treatment Of Inflammatory Diseases, Gang Zhao
Development Of Macromolecular Prodrug Conjugates For The Treatment Of Inflammatory Diseases, Gang Zhao
Theses & Dissertations
Inflammation is the complex biological response to the stimuli triggered by various factors like pathogens, damaged cells, or irritants. Constant uncontrolled acute inflammation may become chronic conditions, leading to significant tissue damage, contributing to a series of chronic inflammatory diseases. Our lab has been working on the different types of inflammatory diseases and has developed multiple macromolecular prodrug conjugates for the better therapeutic efficacy and reduced toxicity. The general approach we have taken is to incorporate small molecules containing monomers into water-soluble and biocompatible polymers, such as N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymers. The superior and the sustained efficacy of those macromolecular …
Development Of Approaches Of Tumor Trapping Enhanced Bb2r-Targeted Radiopharmaceuticals For Prostate Cancer, Wenting Zhang
Development Of Approaches Of Tumor Trapping Enhanced Bb2r-Targeted Radiopharmaceuticals For Prostate Cancer, Wenting Zhang
Theses & Dissertations
The Gastrin-Releasing Peptide Receptor (BB2r) has been intensively investigated as a cancer target over the years. Numerous diagnostic and therapeutic BB2r-targeted agents have been developed for various solid tumors, including prostate cancers, due to the high expression level of BB2r on neoplastic relative to normal tissues. The development of those targeted agents have mainly utilized the modified c-terminal of bombesin(BBN), a peptide that has nanomolar binding affinity to human BB2r. However, a major issue that hinders the clinical translational potential of low-molecular weight, receptor-targted agents, is their short residence time at tumor tissues due to the intrinsically high diffusion and …
Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad
Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad
Theses & Dissertations
RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. However, maintenance of sustained plasma drug levels, for weeks or months, after a single high-level dosing, could improve regimen adherence but, at the same time, affect systemic toxicities. Of these, the most troubling are those that affect the central nervous system (CNS) In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal …