The Guardian of Vision: Intelligent Bacteriophage-Based Eyedrops for Clinical Multidrug-Resistant Ocular Surface Infections.

Clinical multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is the leading cause of refractory bacterial keratitis (BK). However, the reported BK treatment methods lack biosecurity and bioavailability, which usually causes irreversible visual impairment and even blindness. Herein, for BK caused by clinically isolated MDR-PA infection, armed phages are modularized with the type I photosensitizer (PS) ACR-DMT, and an intelligent phage eyedrop is developed for combined phagotherapy and photodynamic therapy (PDT). These eyedrops maximize the advantages of bacteriophages and ACR-DMT, enabling more robust and specific targeting killing of MDR-PA under low oxygen-dependence, penetrating and disrupting biofilms, and efficiently preventing biofilm reformation. Altering the biofilm and immune microenvironments alleviates inflammation noninvasively, promotes corneal healing without scar formation, protects ocular tissues, restores visual function, and prevents long-term discomfort and pain. This strategy exhibits strong scalability, enables at-home treatment of ocular surface infections with great patient compliance and a favorable prognosis, and has significant potential for clinical application.

Experimental and molecular docking investigation of the inclusion complexes between 20(S)-protopanaxatriol and four modified ß-cyclodextrins.

20(S)-Protopanaxatriol (PPT) is a type of ginsenoside isolated from panax notoginseng or ginseng, which is an essential ingredient in functional food, healthcare products and traditional medicine. However, the research and development of PPT are restricted due to its poor solubility. To circumvent the associated problems, a novel bridged-bis [6-(2,2'-(ethylenedioxy) bis (ethylamine))-6-deoxy-ß-CD] (H4) was successfully synthesized. The four inclusion complexes of the mono-[6-(1,4-butanediamine)-6-deoxy-ß-CD] (H1), mono-[6-(2,2'-(ethylenedioxy) bis (ethylamine)-6-deoxy-ß-CD] (H2) and their corresponding bridged bis(ß-CD)s (H3, H4) with PPT were prepared and studied by UV, 1H NMR, 2D ROESY, FT-IR, XRD and SEM technology. The UV-spectrometric titration showed that H1-4 and PPT formed 1:1 inclusion complexes and the binding constants were 297.61, 322.25, 937.88 and 1742 M-1, respectively. It was further revealed that the size/shape-matching relationship, hydrophobic interactions and hydrogen bond interactions play the crucial role in determining the stability of H1-4/PPT inclusion complexes. The solubility of PPT was evidently enhanced by193, 265, 453 and 593 times after the formation of inclusion complexes with H1-4, respectively. Furthermore, molecular docking was used to verify the inclusion mode of H4/PPT inclusion complex and also to investigate the stability of H4/PPT in water phase. The molecular simulation results agreed well with the experimental results. This research provides an effective way to obtain novel PPT-based functional food and healthcare products.