Title page for ETD etd-07082010-183754


Type of Document Master's Thesis
Author Patel, Nipur Rajan
Author's Email Address npate11@tigers.lsu.edu
URN etd-07082010-183754
Title Itraconazole Loaded Poly (lactic-co-glycolic) Acid Nanoparticles for Improved Antifungal Activity
Degree Master of Science in Biological & Agricultural Engineering (M.S.B.A.E.)
Department Biological & Agricultural Engineering
Advisory Committee
Advisor Name Title
Sabliov, Cristina Committee Chair
Damann, Kenneth Committee Member
Enright, Frederick Committee Member
Keywords
  • Itraconazole
  • PLGA (polylactic-co-glycolic acid)
  • Nanoparticles
  • Aspergillus flavus
  • antifungal
  • GFP
  • improved
  • Petri plate
  • activity
Date of Defense 2010-06-29
Availability unrestricted
Abstract
PLGA (polylactic-co-glycolic acid) nanoparticles containing the hydrophobic antifungal Itraconazole (ITZ) were developed to address the need for more efficient means of treating fungal infections. PLGA-ITZ nanoparticles were synthesized using an oil-in-water emulsion evaporation method. The nanoparticles morphology (TEM), size and size distribution, zeta potential (DLS), encapsulation efficiency (UV-VIS), release profile, and antifungal activity were characterized. The blank NPs and loaded PLGA-ITZ NPs were spherical with diameters of 2015 nm, 2321 nm and 22336 nm at 0%, 12.5% and 25% loadings, respectively. All synthesized particles measured a negative zeta potential ranging from -28 to -33 mV. The maximum encapsulation efficiency of ITZ was ~96% at 12.5% w/w theoretical loading. ITZ release showed an initial burst followed by a gradual release profile, with 75% ITZ released over 5 days. PLGA-ITZ nanoparticles inhibited Aspergillus flavus fungal growth more efficiently than free and emulsified ITZ. Quantitative fluorescence experiments performed with a GFP-expressing A. flavus verified that the PLGA-ITZ NPs had superior inhibitory activity at lower ITZ concentrations compared to free and emulsified ITZ drug formulations. PLGA-ITZ nanoparticles (232 nm) completely inhibited Aspergillus flavus growth over 11 days at 0.3 mg/ml ITZ, a concentration 100x less than free and emulsified ITZ. In nanoparticle uptake studies, 203 nm fluorescent PLGA nanoparticles containing coumarin-6 were seen associating with fungal cell surfaces and internalizing efficiently, while 1206 nm particle uptake was sporadic. Quantitative fluorescence experiments of PLGA-ITZ NPs of 232 nm, 630 nm, and 1060 nm showed inhibitory differences at the lowest ITZ concentration of 0.003 mg/ml, and no differences at higher concentrations. The PLGA-ITZ nanoparticle system is envisioned to increase bioavailability of ITZ by improving its aqueous solubility, controlling its release over time and especially increasing antifungal penetration at the cellular level by efficient nanoparticle uptake by cells, thereby elevating antifungal efficacy.
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