Impact of covalently Nile Red and covalently Rhodamine labeled fluorescent polymer micelles for the improved imaging of the respective drug delivery system
| Autor: | Van Nga Nguyen, Gregory Trubitsyn, Gerrit Borchard, Claudia Di Tommaso, Michael Möller, Robert Gurny |
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| Rok vydání: | 2019 |
| Předmět: |
Polymers
Drug Compounding Fluorescence spectrometry Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Micelle Polyethylene Glycols Rhodamine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Oxazines Rhodamine B Micelles Fluorescent Dyes Liposome Drug Carriers Rhodamines Nile red Water General Medicine 021001 nanoscience & nanotechnology chemistry Drug delivery Nanocarriers 0210 nano-technology Hydrophobic and Hydrophilic Interactions Biotechnology Nuclear chemistry |
| Zdroj: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 142 |
| ISSN: | 1873-3441 |
| Popis: | Novel fluorescently labeled poly(ethylene glycol)-poly(hydroxyoctanoic acid) (MPEG-PHOA) block-copolymers were synthesized for the improved visualization of the deriving polymeric micelle drug delivery system. Albeit commonly used, one has to be aware that by simple incorporation of Nile Red (hydrophobic) or Rhodamine B (hydrophilic) as fluorescent compounds in nanocarriers (e.g., nanoparticles, liposomes or micelles) for imaging applications, these fluorescent probes can diffuse out of the carrier system and lead to artefacts due to the concomitant fluorescence loss or areal distribution. In order to inhibit such an uncontrolled diffusion, the Nile Red derivative 2-((9-(diethylamino)-5-oxo-5H-benzo[a]phenoxazin-2-yl)oxy)acetic acid was synthesized and covalently attached to the MPEG-PHOA block-copolymer via a mild Mitsunobu reaction to yield the desired MPEG-PHOA-Nile Red polymer for micelle preparations. Rhodamine B was coupled via its native carboxylic acid group with the copolymer MPEG-PHOA under mild conditions using DMAP, EDC, and NHS. For the proof of concept, aqueous solutions of composite micelles made of 0.5% (w/w fluorescence dye) MPEG-PHOA-dye and MPEG-PHOA copolymers were prepared (“spiking” of the non-labeled base MPEG-PHOA micelles) and characterized by transmission electron microscopy (TEM), dialysis and fluorescence spectrometry. The fluorescence intensity of the Nile Red in the solutions was followed up at physiological temperatures and pH values (37 °C, pH = 7.4 PBS buffer 0.01 M) over a period of 8 weeks. The labeled and non-labeled micelle formulations were tested in vitro in cells (Rhodamine-micelle formulations), then in vivo in a case study of an ophthalmic application (Nile Red micelle formulations). Both in vitro and in vivo experiments revealed a significant improvement of fluorescence stability of the MPEG-PHOA-dye formulations, facilitating the investigations on tracing the micelles and their stability. The results clearly demonstrate the value of the novel Nile Red and Rhodamine derivatives, whose simple synthesis and covalent attachment may easily be transferred to other nanosized polymeric drug delivery systems, e.g., MPEGylated or non-MPEGylated PLA/PLGA nanoparticles and be envisioned for novel theranostic systems. |
| Databáze: | OpenAIRE |
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