Synthesis and Characterization of Polymeric Nanoparticle Structures for Control Drug Delivery in Cancer Therapies and Temperature Effects on Drug Release

Persistent Link:
http://hdl.handle.net/10150/308903
Title:
Synthesis and Characterization of Polymeric Nanoparticle Structures for Control Drug Delivery in Cancer Therapies and Temperature Effects on Drug Release
Author:
Lucero Acuna, Jesus Armando
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
In this research a variety of drug delivery systems were synthesized and characterized. For the most part, these consisted of a matrix of poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and polyvinyl alcohol (PVA) containing encapsulated anticancer drugs as chemotherapy agents. The drug release from biodegradable nanoparticles was analyzed mathematically using new approaches that simultaneously incorporates the three major mechanisms of release: initial burst, nanoparticle degradation-relaxation, and diffusion. The theoretical release studies were corroborated experimentally by evaluating the cytotoxicity effectiveness of PHT-427-loaded nanoparticles over pancreatic cancer cells in vitro. These studies showed that the encapsulated PHT-427 drug in the nanoparticles is more accessible and thus more effective when compared with the drug alone. Also, the PHT-427-loaded nanoparticles cytotoxicity was evaluated in vivo studies with pancreatic tumors. The results show that the drug is more effective when is loaded into polymeric nanoparticles compared to drug alone, by reducing orthotopic pancreatic tumor growth. In addition, a selection of hydrophobic to hydrophilic drugs were encapsulated into polymeric nanoparticles to find optimal drug loadings by using single or double emulsification techniques. The release of these drugs from PLGA nanoparticles was evaluated to determine the overall release profile characteristics. The encapsulation of the drug pemetrexed was improved by using polyethileneimine. The high positive charge density of polyethileneimine causes a strong electrostatic interaction with the carboxylic acids of pemetrexed; this complex decreases the solubility of pemetrexed and boosts the encapsulation efficiency. Additionally, a drug release mathematical analysis that considers the effects of the temperature of release was effectively established. The analysis was performed by using two different models: the first one simultaneously incorporates the mechanisms of initial burst and nanoparticle degradation - relaxation, and the second model, besides of the mechanisms of the first model, includes the diffusion of the drug. Both models were successfully employed to describe the experimental release of rhodamine 6G from PEGylated nanoparticles at different temperatures. From the parameters obtained by the fit using each model, it was possible to define a set of new relations of the form of Arrhenius to estimate the parameters of release at other temperatures.
Type:
text; Electronic Dissertation
Keywords:
Mathematical modeling; Nanoparticles; Pancreatic cancer; PLGA; Chemical Engineering; Drug delivery
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemical Engineering
Degree Grantor:
University of Arizona
Advisor:
Guzman, Roberto

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleSynthesis and Characterization of Polymeric Nanoparticle Structures for Control Drug Delivery in Cancer Therapies and Temperature Effects on Drug Releaseen_US
dc.creatorLucero Acuna, Jesus Armandoen_US
dc.contributor.authorLucero Acuna, Jesus Armandoen_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractIn this research a variety of drug delivery systems were synthesized and characterized. For the most part, these consisted of a matrix of poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and polyvinyl alcohol (PVA) containing encapsulated anticancer drugs as chemotherapy agents. The drug release from biodegradable nanoparticles was analyzed mathematically using new approaches that simultaneously incorporates the three major mechanisms of release: initial burst, nanoparticle degradation-relaxation, and diffusion. The theoretical release studies were corroborated experimentally by evaluating the cytotoxicity effectiveness of PHT-427-loaded nanoparticles over pancreatic cancer cells in vitro. These studies showed that the encapsulated PHT-427 drug in the nanoparticles is more accessible and thus more effective when compared with the drug alone. Also, the PHT-427-loaded nanoparticles cytotoxicity was evaluated in vivo studies with pancreatic tumors. The results show that the drug is more effective when is loaded into polymeric nanoparticles compared to drug alone, by reducing orthotopic pancreatic tumor growth. In addition, a selection of hydrophobic to hydrophilic drugs were encapsulated into polymeric nanoparticles to find optimal drug loadings by using single or double emulsification techniques. The release of these drugs from PLGA nanoparticles was evaluated to determine the overall release profile characteristics. The encapsulation of the drug pemetrexed was improved by using polyethileneimine. The high positive charge density of polyethileneimine causes a strong electrostatic interaction with the carboxylic acids of pemetrexed; this complex decreases the solubility of pemetrexed and boosts the encapsulation efficiency. Additionally, a drug release mathematical analysis that considers the effects of the temperature of release was effectively established. The analysis was performed by using two different models: the first one simultaneously incorporates the mechanisms of initial burst and nanoparticle degradation - relaxation, and the second model, besides of the mechanisms of the first model, includes the diffusion of the drug. Both models were successfully employed to describe the experimental release of rhodamine 6G from PEGylated nanoparticles at different temperatures. From the parameters obtained by the fit using each model, it was possible to define a set of new relations of the form of Arrhenius to estimate the parameters of release at other temperatures.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectMathematical modelingen_US
dc.subjectNanoparticlesen_US
dc.subjectPancreatic canceren_US
dc.subjectPLGAen_US
dc.subjectChemical Engineeringen_US
dc.subjectDrug deliveryen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemical Engineeringen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorGuzman, Robertoen_US
dc.contributor.committeememberGuzman, Robertoen_US
dc.contributor.committeememberMuscat, Anthonyen_US
dc.contributor.committeememberPhilipossian, Araen_US
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