Green Preparation Process, Characterization and Antitumor Effects of Doxorubicin–BSA–Dextran Nanoparticles

Abstract

In this report, we developed a simple and green process of simultaneous formation of doxorubicin-BSA-dextran nanoparticles in aqueous solution and high-effective encapsulation of doxorubicin. In the presence of BSA-dextran conjugates, which were produced by Maillard reaction, a binding of doxorubicin with BSA can suppress the self-aggregation of unprotonated doxorubicin. After a heat treatment, the gelation of BSA results in a formation of the nanoparticles and the doxorubicin was fixed inside the nanoparticles. The dextran shell makes the nanoparticles dispersible in solution. The nanoparticles have a spherical morphology and a hydrodynamic radius of about 90 nm. Importantly, the nanoparticles can significantly prolong the life of murine ascites hepatoma H22 tumor-bearing mice.

Enhanced tumor delivery and antitumor response of doxorubicin loaded albumin nanoparticles formulated based on a Schiff base

“…As the BSA/DOX⋅HCl ratio decreased, the particle size and DLE increased, while the DEE decreased (Table 2). Compared with the DOX-BSA-Dextran-NPs reported by Deng et al, 24 the DOX-BSA-V-NPs possessed a similar DLE and DEE at the same BSA/DOX⋅HCl ratio, but a slightly larger size. For the sake of investigating the in vivo behavior, a BSA/DOX⋅HCl ratio of 10:1, a comparable size as the DOX-BSA-NPs (vanillin free), was selected.…”

“…Because of the comparatively higher solubility of protonated DOX and weaker interactions between DOX and NPs at lower pH values, both the free DOX and DOX-BSA-V-NPs showed faster diffusion/release in pH 6.5 buffers than in 7.4 buffers. 22,24 Moreover, the NPs showed quicker and greater release in greater concentration GSH solutions (20 mM) than in lower GSH concentration solutions (10 μM) due to the presence of a large number of disulfide bridges in the NPs. In addition, the release curve of DOX-BSA-V-NPs in PBS buffer (pH 7.4) was similar to that in 10 μM GSH (pH 7.4), suggesting that the appearance of lower GSH concentrations did not significantly affect the release behavior.…”

“…After 10 days of inoculation, the animals were sacrificed by cervical dislocation. 22,24 Subsequently, dissection was done, and the tumors and hearts were removed for the following studies. The solid tumors were harvested and measured, while the hearts and tumors were sectioned for histological evaluation by hematoxylin and eosin (HE) staining.…”

“…Therefore, the interaction between DOX and BSA-V-NPs was enhanced and as a result, the BSA-V-NPs possessed a higher DLE and a more compact structure (Table 1). 24 However, as the amount of DOX⋅HCl was fixed, when all the DOX molecules in the system were unprotonated, the DLE and DEE would be relatively constant. Herein, a pH of 7.4 was chosen in the following study due to the satisfactory encapsulation efficiency and drug loading.…”

“…Compared with the DLS data, the particle size of TEM was smaller, since the TEM captured the images of the dried NPs, whereas the DLS determined the hydrodynamic diameter. 24 The conformational changes of BSA were observed by the CD spectra. As shown in Figure 2, the spectra of both DOX-loaded and DOX-free BSA-V-NPs exhibited two negative peaks ~210 and 220 nm, which were the characteristic bands of the α-helix structure.…”