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Preparation and Characterization of Albumin Nanoparticles of Paclitaxel-Triphenylphosphonium Conjugates: New Approach to Subcellular Targeting.
- Source :
-
Drug research [Drug Res (Stuttg)] 2020 Feb; Vol. 70 (2-03), pp. 71-79. Date of Electronic Publication: 2020 Jan 27. - Publication Year :
- 2020
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Abstract
- Mitochondria have been recognized as important targets in cancer therapy due to their role in the respiratory process of cells. One approach employed for mitochondrion targeting is conjugation of a delocalized cation such as triphenylphosphonium (TPP), with antineoplastic agents, for instance paclitaxel (PTX). In cell cytoplasm, TPP-PTX can come close to mitochondria due to its high positive charge, which has a strong tendency toward the enhanced negative charge of mitochondria. The esteric bond of TPP-PTX can break down in the acidic environment of tumor cells and release the PTX, which can act directly on mitochondria to kill tumor cells. TPP-PTX was synthesized in three steps: Succinic anhydride (SUC) reacted with PTX to achieve succinyl paclitaxel (SUC-PTX), which has an acid-labile esteric bond. Then 2-triphenylphosphonium ethylammonium (ATPP) was prepared by attaching 2-bromoethylammunium bromide to TPP. Finally, a TPP-PTX prodrug was synthesized by attaching these materials. The products of all steps were characterized by thin-layer chromatography (TLC), infrared spectroscopy (IR), and nuclear magnetic resonance ( <superscript>1</superscript> H NMR, <superscript>13</superscript> C NMR). The purity of the products was determined by HPLC methods. TPP-PTX, as a prodrug, was loaded in to human serum albumin (HSA) nanoparticles by a method inspired by nab-technology with 130-160 nm particle size distribution, PdI=0.166 and Zeta potential -12.6 mV.<br />Competing Interests: The authors declare that they have no conflict of interest.<br /> (© Georg Thieme Verlag KG Stuttgart · New York.)
- Subjects :
- Antineoplastic Agents, Phytogenic administration & dosage
Antineoplastic Agents, Phytogenic chemical synthesis
Antineoplastic Agents, Phytogenic chemistry
Chemistry, Pharmaceutical
Chromatography, High Pressure Liquid
Drug Carriers chemistry
Drug Liberation
Mitochondria metabolism
Organophosphorus Compounds chemical synthesis
Paclitaxel chemical synthesis
Paclitaxel chemistry
Particle Size
Prodrugs
Serum Albumin, Human chemistry
Drug Delivery Systems
Nanoparticles
Organophosphorus Compounds chemistry
Paclitaxel administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2194-9387
- Volume :
- 70
- Issue :
- 2-03
- Database :
- MEDLINE
- Journal :
- Drug research
- Publication Type :
- Academic Journal
- Accession number :
- 31986546
- Full Text :
- https://doi.org/10.1055/a-1016-6889