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Characterization and determination of protein-protein interactions (PPIs) plays an important role in molecular biological science. In this study, the effect of aminoglycosides (AGs: streptomycin, gentamycin, lincomycin and clindamycin) on interactions between bovine serum albumin (BSA) was evaluated employing imaging and probing adhesion event by AFM. Multi-spectroscopy and molecular docking were supplementary to investigate the acting forces of the effect. AFM measurements revealed the aggregation of BSA grains and changes of adhesion forces at single molecule level. With adhesion forces between BSA pairs decomposed by Poisson method, specific forces in streptomycin, gentamycin, lincomycin and climdamycin were obviously decreased with the rate of 33.1%, 26.4%, 32.3% and 31.3% while non-specific forces slightly decreased with 5.5%, 3.3%, 4.0% and 7.7%. Combined with results of multi-spectroscopy as well as molecular docking, the whole determination showed AGs affected PPIs by multiple forces, where the hydrogen bonding and hydration effect were the main reasons. The binding of drugs and proteins acted by hydrogen bonding affected the interaction forces between BSA. Consequently, AFM was proposed to be an effective and precise tool in application including evaluating the effects of exogenous compounds on biomacromolecular interactions and rapid screening of drug candidates to avoid potential damages in disease treatment.

Acyclovir (ACV), an analog of 2′-deoxyguanosine, exhibits poor bioavailability due to limited permeability. In this study, the aim was to improve the bioavailability and permeability of ACV. N,N,N-trimethyl-O-octadecyl chitosan (TMSC) was synthesized by covalently bonding a long alkyl chain and a quaternary ammonium group onto chitosan. The chemical structure of TMSC was characterized by Fourier transform infrared (FT-IR) spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetry (TG), and differential thermogravimetry (DTG). The biological safety of TMSC was evaluated using a hemolysis experiment, which resulted in a hemolysis rate of 6.63% at the highest concentration (3 mg/mL). TMSC was used to prepare acyclovir nanoparticle (ACV NP) based on the Box–Behnken design, and characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS) to determine size and morphology. Furthermore, the permeability of ACV NP was investigated using a non-everted intestinal sac model. ACV NP exerted a 1.9-fold higher effect on the ileum than ACV. In vivo, the relative bioavailability of ACV NP was ∼4.5-fold greater than that of the ACV suspension. These results suggest that ACV NP augment permeability and effectiveness of ACV.