Nanoscopic Characterization of Stearic Acid Release from Bovine Serum Albumin Hydrogels

Abstract

The release behavior of 16‐doxyl stearic acid (16‐DSA) from hydrogels made from bovine serum albumin (BSA) is characterized. 16‐DSA serves as a model tracer molecule for amphiphilic drugs. Various hydrogel preparation procedures are tested and the fatty acid release from the different gels is compared in detail. These comparisons reach from the macroscopic level, the viscoelastic behavior via rheological characterization to changes on the nanoscopic level concerning the secondary structure of the protein during gelation through infrared (ATR‐IR) spectroscopy. 16‐DSA‐BSA interaction via continuous wave electron paramagnetic resonance (CW EPR) spectroscopy in addition gives a nanoscopic view of small molecule–hydrogel interaction. The combined effects of fatty acid concentration, hydrogel incubation time, and gelation procedures on release behavior are studied via CW EPR spectroscopy and dynamic light scattering (DLS) measurements, which provide deep insight on the interaction of 16‐DSA with BSA hydrogels and the nature and size of the released components, respectively. It is found that the release rate of the fatty acid from BSA hydrogels depends on and can thus be tuned through its loading percentage, duration of hydrogel formation and the type of gelation methods. All of the results confirm the potential of these gels as delivery hosts in pharmaceutical applications allowing the sustained release of drug.

Molecular-Level Release of Coumarin-3-Carboxylic Acid and Warfarin-Derivatives from BSA-Based Hydrogels

“…4-Hydroxy TEMPO-labeled coumarin-3-carboxylic acid (SL-CCS) and 4-carboxy-TEMPO-labeled warfarin (SL-WFR), synthesized previously [39], were used in this research. In our recent work [20], we introduced a concise notation, BSAi(θ, p, t, r), to describe the gelation technique (i), which can be either thermally (T) or pH (P) induced methods, temperature (θ) and pH (p) of hydrogel preparation, incubation time (t, in minutes), and time-release (r, in hours) indicating the release of drug over a specific time, respectively. For instance, BSAT (65,7.4,5,48) refers to the thermally prepared gel at 65 °C for 5 min and pH 7.4, and the release behavior was studied 48 h after gelation.…”

“…SL-CCS and SL-WFR powders were dissolved separately in DMSO to obtain 26 mM stock solutions and added into the BSA precursor solution with three different drug:BSA molar ratios into glass vials. Hydrogels were prepared by adopting the procedures described in our paper [20]. Thermally induced gels were obtained by keeping the vials in a thermomixer at 65 • C and 59 • C, above and below the denaturation temperature of BSA, while some hydrogels were prepared at 37 • C by the addition of 2 M HCl and lowering the pH to 3.5 by the so-called pH induced method.…”

“…Previously, our group synthesized various spin-labeled pharmaceuticals (SLP) including warfarin and coumarin-3-carboxylic acid (see Figure 1B,C) and analyzed drug binding to human serum albumin in solution with serum-like concentrations via the continuous-wave EPR spectroscopic approach [39]. Furthermore, the release of 16-doxyl stearic acid (16-DSA) as a model drug from BSA hydrogels and the nanoscopic properties of released components has been studied extensively [20]. In the present report, we aimed at developing and comparing controlled delivery systems based on BSA hydrogels and spin-labeled coumarin-3-carboxylic acid (SL-CCS) and warfarin (SL-WFR) as our candidate drugs to investigate the release behavior from the prepared gels.…”

“…By analyzing these fluctuations, information about the diffusion correlation and particle size can be obtained. DLS is one of the most popular techniques used as a non-destructive method to characterize complex liquids, proteins, and polymer structures [20,42,43].…”

“…However, the G value of BSA T (65, 7.4) was, as expected, considerably higher than that of the BSA T (59, 7.4). In our previous work [20], we extensively studied changes in the secondary structure of BSA during gelation.…”