Optimization of the Preparation and Characterization of Tannylated-Albumin Nanoagents

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Communication

DOI 10.1007/s13233-020-8141-x

www.springer.com/13233 pISSN 1598-5032 eISSN 2092-7673

Optimization of the Preparation and Characterization of TannylatedAlbumin Nanoagents Yeong Jun Song Sung Yun Jung Jin Hyuk Kim Kyeongsoon Park*

Department of Systems Biotechnology, Chung-Ang University, Anseong, Gyeonggi 17546, Korea

Received April 2, 2020 / Revised June 30, 2020 / Accepted July 7, 2020

Abstract: We optimized the preparation of tannylated-human serum albumin (TAHSA) nanoagents including indocyanine green (ICG) and lobeglitazone (Lobe)-loaded complexes by simple mixing and characterized them. We set the optimal pH at 5 and the optimal weight ratio of [TA]/[HSA] at 1.5 when considering the redispersion of the prepared suspensions in PBS (pH 7.4) and incubation at 37 °C for the preparation of ICG and/or Lobe-loaded TA-HSA complexes. The immobilization of methoxy polyethylene glycol (mPEG) molecules on TA-HSA-ICG complexes significantly reduces the mean and Z-average sizes of these complexes from the microscale to the nanoscale. Moreover, the use of ICG increases the drug loading efficiency when preparing mPEGTA-HSA-ICG/Lobe.

Keywords: tannic acid, albumin, protein-based carrier, nanoagent.

1. Introduction Many organic and inorganic materials have been produced to improve the sensitivity of medical diagnosis or to serve as carriers to deliver therapeutic drugs.1 Compared to metals,2 silicone,3 and other polymers,4 biological proteins and lipids have various advantages, such as high biocompatibility, lower toxicity, and reproducible large-scale production.5 Thus, these biological materials are more useful for the fabrication of translational therapeutic nanoagents.6 Albumin, a water-soluble small globular protein, has shown remarkable promise as a delivery carrier due to the chemical stability, biodegradability, and biocompatibility of albumin-based vehicles.5,7-9 In addition, albumin-based drug carriers increase the bioavailability and stability of pharmaceuticals in biological fluids.10 Thus, they have been applied to deliver various therapeutic drugs to tumor tissues.11-13 However, the preparation of albuminbased nanoparticles involves time-consuming processes, such as solvent evaporation,11,12 heating to high temperatures,13 and homogenization.11 Tannic acid (TA) is a plant-derived polyphenol found in various fruits, olives, cacao, and vegetables, among others.14 TA has recently been used as a multi-functional coating molecule for organic and inorganic surfaces of numerous shapes, such as films and particles, via covalent and noncovalent interactions.15-17 Moreover, previous studies have reported that TA strongly binds to biomacromolecules, including DNA18 and proteins,19-21 via mul-

tiple hydrogen bonds and hydrophobic interactions,22 thereby producing TA-biomacromolecule complexes. Based on the strong interactions between TA and biomacromolecules, we prepared a TA-modified human serum albumin (named tannylated-albumin; TA-HSA) nanoagent that contained indocyanine green (ICG; a near-infrared