Browsing by Subject "PLGA"
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Item ANTIBODY ENCAPSULATION WITHIN POLYMERIC NANOPARTICLES(2014-03) Gdowski, Andrew; Ranjan, Amalendu; Mukerjee, Anindita; Vishwanatha, JamboorAntibodies represent a large class of drugs that have a number of different therapeutic uses. However, side effects can persist due to off target toxicity that may result when the antibody affects a tissue other than where it is intended to act. The use of targeted nanoparticles is one potential way to deliver an antibody to a specific organ where the antibody can be released in a controlled manner and limit side effects. Purpose (a): The purpose of this study is to characterize a human monoclonal antibody encapsulated within a poly(lactic-co-glycolytic) acid (PLGA) nanoparticle. We hypothesized that encapsulation of an antibody within PLGA nanoparticles is feasible and will release in a favorable manner. Methods (b): AnnexinA2 (AnxA2) IgG antibody was encapsulated within PLGA nanoparticles. Encapsulation efficiency and release kinetics were determined using polyacrylamide gel electrophoresis and coomassie brilliant blue staining. Dynamic light scattering (DLS) from Malvern Zetasizer was used to determine hydrodynamic size and zetapotential. Western blot was accomplished with cell lysates from known AnxA2 expressing cell lines to determine functionality of antibody once released from PLGA nanoparticles. Results (c): Our results show acceptable encapsulation efficiency of AnxA2 within the PLGA nanoparticle. Nanoparticles were formed in a favorable monodisperse manner. Release experiments demonstrate that AnxA2 is released in a controlled manner over a period of 15 days. In addition after release the antibody maintained functionality as evidenced through Western Blot analysis. Conclusions (d): We conclude that encapsulation of IgG monoclonal antibodies is feasible, exhibits sustained release kinetics, and maintains functionality upon release. Further, this encapsulation technique may be used as a method to load antibodies in targeted nanoparticles for release in a tissue specific manner.Item Development and Characterization of Methylene Blue Oleate Salt-Loaded Polymeric Nanoparticles as a Treatment for Glioblastoma(2016-12-01) CastaƱeda-Gill, Jessica M.; Jamboor K. Vishwanatha; Amalendu P. Ranjan; Shaohua YangGlioblastoma (GBM) is the most common and aggressive primary brain tumor in older adults, resulting in an average survival of 15 months post-diagnosis and treatment. While recent research has provided essential information, GBM relapse following traditional combinatorial regimens (surgery, radiation, and chemotherapy) is common, necessitating the development of more effective, less toxic therapies. Methylene blue (MB), a dye with noted medicinal applications, has received recent consideration as a potential neurotherapeutic due to its ability to infiltrate the blood-brain barrier (BBB), improve processes within distinct brain cell compartments and types, and preferential accumulation in the brain. While MB displays these advantages, one drawback is increased administration to produce therapeutic effects, leading to excessive brain deposition and potential neurotoxicity. A common method to enhance drug delivery is via encapsulation in submicron-sized nanoparticles (NPs) composed of the biodegradable/biocompatible co-polymer, poly(lactic-co-glycolic) acid (PLGA). We have previously shown their application as potential cancer therapies, as well as preferential brain accumulation. Thus, our goal was to develop MB-loaded NPs capable of permeating the BBB in order to treat GBM, based on our hypothesis that encapsulation of MB into PLGA NPs would enhance accumulation in cancerous regions, resulting in reduced tumor size and prolonged survival. In this study, we prepared a methylene blue-oleate salt conjugate (MBOS) to enhance its stability, then formulated and characterized methylene blue oleate salt-loaded polymeric nanoparticles (MBOSNPs) via size, surface charge, drug loading (DL), and encapsulation efficiency (EE). We also analyzed their in vitro effects to establish biological, and potentially therapeutic, activity. As a result, we obtained preparations physio-chemically comparable to other at 162.4nm, with a surface charge of -31.7 and DL and EE values of 2.2% and 29.2%, respectively. Next, MB(OS)NPs were determined to produce a peak drug release at 24hrs, and induce cytotoxicity comparable to, if not better than, free drug, in two GBM cell lines. Additionally, MB(OS)NPs enhanced cellular metabolism, a capability noted in free MB. Lastly, animal studies confirmed enhanced BBB permeation by MBOSNPs compared to free MBOS, demonstrating their therapeutic potential.Item FORMULATION AND CHARACTERIZATION OF POLYMERIC NANOPARTICLES FOR CANCER TREATMENT CONCEPTUAL APPROACH(2013-04-12) CastaƱeda-Gill, Jessica M.Purpose: Cancer treatments currently used in the clinic have demonstrated their effectiveness over the last 50 years, however, little has been done to improve their resultant toxic side effects. Most chemotherapy and radiation treatments produce varying outcomes in patients, from hair loss to nausea to infection and metastasis; this begs the question as to why there has been minimal research aimed at developing less harmful therapies. With the advent of nanotechnology during the last few decades, the drug development process has switched to biodegradable nanoparticle (NP) drug delivery systems as a means to improve drug efficacy, while reducing toxic side effects. In this project, formulation and characterization of biodegradable polylactide-co-glycolide (PLGA) NPs is discussed and performed, in order to provide cancer therapy options that could be more effective and less harmful. Methods: PLGA NPs have been used to encapsulate hydrophobic drugs, small molecules, DNA/RNA, etc. effectively, with high drug loading, depending on the formulation. In this project, PLGA NPs were used to encapsulate cancer therapy drugs using sonication and established water-in-oil-in water (W/O/W) procedures. Following formulation, the PLGA NPs were characterized via a Nanotrac particle size analyzer. The aforementioned PLGA NPs can now be used in in vitro and in vivo studies to determine their effectiveness as cancer treatments. Results: Several PLGA NP formulations were produced, with different loading components and sizes. Implementation of sonication and W/O/W emulsion techniques were important factors that affected NP size and drug loading. Regardless, from batch to batch, for each formulation, NP size was consistent (140-190nm). The small size of the PLGA NPs (<200nm) demonstrates the increased likelihood of uptake by cancer cells, either in vitro or in vivo, which is important for effective treatment. Conclusions: With the dawn of nanomedicine, particularly cancer therapy, the development of better, less harmful drugs is more likely. Through the use of PLGA NPs, an FDA-approved, biodegradable drug delivery system, cancer treatments could be more effective, due to the potential for targeting of cancer cells and reduced toxic side effects, ultimately increasing a patient's quality of life. Due to their small size, flexibility of content loading, surface functionalization, biodegradability/biocompatibility, and enhanced uptake by cancer cells, PLGA NPs could improve treatments and patient prognosis.