title: PLGA nano/microparticles loaded with cresyl violet as a tracer for drug delivery: Characterization and in-situ hyperspectral fluorescence and 2-photon localization.
abstract: Here we present the production, characterization and in-vivo assessment of cresyl violet-loaded biodegradable PLGA nano/microparticles (CV-NP and CV-MP). We demonstrate that the beneficial spectral characteristics of cresyl violet make it suitable as a tracer for particle-based drug delivery using both hyperspectral wide field and two-photon excited fluorescence microscopy. Particles were prepared using a cosolvent method, after which the physicochemical properties such as morphology, particle size, drug entrapment efficiency, drug loading and in vitro drug release behavior were measured in addition to spectroscopic properties, such as absorption, fluorescence and infrared spectra. The particles were then tested in an in vivo mouse model to assess their biodistribution characteristics. The location and integrity of particles after injection was determined using both hyperspectral fluorescence and two-photon microscopy within intact organs in situ. Our results show that cresyl violet is efficiently entrapped into PLGA particles, and that the particles are spherical in shape, ranging from 300 to 5070nm in diameter. Particle biodistribution in the mouse was found to depend on particle size, as expected. Cresyl violet is shown to be an ideal tracer to assess the properties PLGA particle-based drug delivery in combination with our novel multi-scale optical imaging techniques for in-situ particle localization.
authors: Laboratory of Photochemistry and Nanobiotechnology, University of Brasília, Brasília, Brazil; Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY, United States. Electronic address: clunardi@unb.br.
authors: Claure N
authors: CN
authors: Lunardi
authors: Laboratory of Photochemistry and Nanobiotechnology, University of Brasília, Brasília, Brazil; Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY, United States.
authors: Anderson J
authors: AJ
authors: Gomes
authors: Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY, United States.
authors: Sandeep
authors: S
authors: Palepu
authors: Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY, United States.
authors: P Thilanka
authors: PT
authors: Galwaduge
authors: Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY, United States.
authors: Elizabeth M C
authors: EM
authors: Hillman
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000737:chemistry*; D016503:Drug Delivery Systems; D005453:Fluorescence; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000737:chemistry*; D008819:Mice, Nude; D036641:Microscopy, Fluorescence, Multiphoton; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009928:Organ Specificity; D010316:Particle Size; D017785:Photons; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D048588:Benzoxazines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C028911:cresyl violet; D019344:Lactic Acid
keywords: Biodistribution; Cresyl violet; Hyperspectral fluorescence; PLGA; Two-photon microscopy