Interaction of Mitoxantrone-Loaded Cholesterol Modified Pullulan Nanoparticles with Human Serum Albumin and Effect on Drug Release

Abstract

To clarify nanoparticle-protein interaction and their action characteristics, the interactions between MTO-CHP NPs and human serum albumin (HSA) were studied by isothermal titration calorimetry (ITC), fluorescence spectroscopy, dynamic light scattering (DLS), and circular dichroism spectroscopy (CD). Hydrophobically modified pullulan (CHP) nanoparticles (NPs) loaded with mitoxantrone (MTO) were prepared (MTO-CHP NPs) with size 166.9 nm. The spherical shape was verified by transmission electron microscopy (TEM). The ITC results demonstrated an interaction between MTO-CHP NPs mainly by hydrophobic interaction force, electrostatic force, and hydrogen bonding. The mean binding constant KA was 0.832×104 M−1 and mean HSA coverage 0.939±0.302. MTO-CHP NPs could quench the fluorescence intensity of HSA, which gradually decreased to be balanced in 9 h and indicated the completion of the complexation. The size and zeta potential changes of the combined particle were dynamically detected with DLS at 0, 3, 6, 9, 12, 15, and 18 h. When the reaction was completed at 9 h, the particle size and potential remained stable, accompanied by a size change from 89.91 to about 145 nm and potential change from -15 to -3 mV, respectively. The results of CD measurement showed that the change in ellipticity of HSA at 208 nm was similar to the fluorescence spectra and DLS measurements with MTO-CHP NPs combined with HSA. At the beginning of the reaction, the proportion of α-helix was 52.3% to 43.7%, which decreased by 39.1% at compound stabilization. The release of MTO from MTO-CHP NPs at pH=5.6 was significantly accelerated, whereas that of MTO from HSA-MTO-CHP NPs was significantly reduced, and the drug release was significantly slowed down even under acidic conditions, which indicates the beneficial effect of HSA on the persistence and stability of the HSA-MTO-CHP NP compound.

Human Serum Albumin in the Presence of AGuIX Nanoagents: Structure Stabilisation without Direct Interaction

“…The alpha helix content found for pure HSA at 47 μM and 37 °C was close to 53 ± 2%. This result is in agreement with the values of 67% [ 38 ], 52% [ 43 ] and 34% [ 44 ] obtained for HSA at 2 μM, 15 μM and 150 μM, respectively (a summary of the alpha helix contents as function of the protein concentration is shown in Supplementary Figure S2 ). In the presence of AGuIX ® , the protein secondary structure was found constant for the ratios of AGuIX ® per HSA below 22:1.…”

Oxidative modifications and structural changes of human serum albumin in response to air dielectric barrier discharge plasma

“…The total content of the α-helix decreases from 45.34% to 14.90% after treatment for 8 min, whereas the β-sheet increases from 20.42% to 40.71% (Table 3). The αhelix content of untreated HSA ranges from 43.7% to 52.3%, as reported by Yuan et al, similar to our results [39]. Moreover, the slight red shift of amide A (∼3200 cm −1 ) and the slight blue shift of amide B (∼3076 cm −1 ) are related to the hydrogen bonding and secondary structure changes [37,40].…”

Peptide‐Based Recognition Agents of Histamine: A Biopanning Approach with Enhanced Specificity

“…However, when ΔH > 0 and ΔS > 0, the interaction is primarily attributed to hydrophobic interactions. [33] In light of these findings, we conclude that hydrophobic interactions play a significant and dominant role in the interaction between HBF26 and histamine.…”