Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 22:28:0033.
doi: 10.34133/bmr.0033. eCollection 2024.

Thermosensitive Polyhedral Oligomeric Silsesquioxane Hybrid Hydrogel Enhances the Antibacterial Efficiency of Erythromycin in Bacterial Keratitis

Lan Zheng  1 , Ying Chen  2 , Yi Han  1   3 , Jingwei Lin  1 , Kai Fan  2 , Mengyuan Wang  1 , Ting Teng  3 , Xiuqin Yang  2 , Lingjie Ke  2 , Muyuan Li  4 , Shujia Guo  1 , Zibiao Li  5 , Yunlong Wu  2 , Cheng Li  1   4   5
Affiliations

Thermosensitive Polyhedral Oligomeric Silsesquioxane Hybrid Hydrogel Enhances the Antibacterial Efficiency of Erythromycin in Bacterial Keratitis

Lan Zheng et al. Biomater Res. .

Abstract

Bacterial keratitis is a serious ocular infection that can impair vision or even cause blindness. The clinical use of antibiotics is limited due to their low bioavailability and drug resistance. Hence, there is a need to develop a novel drug delivery system for this infectious disease. In this study, erythromycin (EM) was encapsulated into a bifunctional polyhedral oligomeric silsesquioxane (BPOSS) with the backbone of the poly-PEG/PPG urethane (BPEP) hydrogel with the aim of improving the drug efficiency in treating bacterial keratitis. A comprehensive characterization of the BPEP hydrogel was performed, and its biocompatibility was assessed. Furthermore, we carried out the evaluation of the antimicrobial effect of the BPEP-EM hydrogel in S. aureus keratitis using in vivo mouse model. The BPEP hydrogel exhibited self-assembling and thermogelling properties, which assisted the drug loading of drug EM and improved its water solubility. Furthermore, the BPEP hydrogel could effectively bind with mucin on the ocular surface, thereby markedly prolonging the ocular residence time of EM. In vivo testing confirmed that the BPEP-EM hydrogel exerted a potent therapeutic action in the mouse model of bacterial keratitis. In addition, the hydrogel also exhibited an excellent biocompatibility. Our findings demonstrate that the BPEP-EM hydrogel showed a superior therapeutic effect in bacterial keratitis and demonstrated its potential as an ophthalmic formulation.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1.
Fig. 1.
Schematic representation of the synthesis of BPEP-EM hydrogels for the therapy of bacterial keratitis.
Fig. 2.
Fig. 2.
(A) Transmittance of aqueous BPEP solutions (2 wt %) in temperature range of 25 to 75 °C. (B) LCST determination from the derivative plots of (A). (C) Size distribution (by intensity) of micelles in aqueous 0.5BPEP solution at different concentration and temperature. (D) Mean particle size related to temperature and concentration for 2BPEP. (E) Mean particle size related to BPEP type and concentration at 70 °C.
Fig. 3.
Fig. 3.
(A) Illustration for possible mechanism of phase transition in aqueous BPEP solution. (B) Phase diagram of 1BPEP determined by tube inverting method. (C) Rheological properties of 1BPEP (8 wt %) sample in temperature sweep. (D) Rheological properties of 1BPEP (8 wt %) sample in time ramp.
Fig. 4.
Fig. 4.
(A) Transmittance of 1B-EM, 2B-EM, and F127-EM hydrogels and EM in the wavelength range of 0 to 780 nm. (B) Residual weight ratio of 1BPEP, 2BPEP, and F127 hydrogels with time. (C) Doxorubicin release curve of 1BPEP, 2BPEP, and F127 hydrogels. Surface plasmon resonance sensograms of (D) 1BPEP and (E) 2BPEP (3.906 to 62.50 μM) binding to mucin in mouse cornea.
Fig. 5.
Fig. 5.
(A) Viability of HCE cells after 24 h of the addition of different formulations using MTT assay. (B) Percentage of living HCE cells cultured in different formulations for 24 h. (C) LIVE/DEAD assay showing HCE cells cultured in different formulations for 24 h. (D) Images of cell morphology (F-actin, green fluorescence) and nucleus (DAPI, blue fluorescence) of HCE cells cultured in different formulations of culture media for 24 h. Data presented as mean ± SEM (n = 6).
Fig. 6.
Fig. 6.
(A) and (B) show the size of the inhibition zone after treatment with various formulations. Data presented as mean ± SEM (n = 3).
Fig. 7.
Fig. 7.
In vivo evaluation of different formulations for bacterial keratitis. (A) Slit lamp images of eyes in each group on days 1, 3, 5, and 7. (B) OCT images of eyes in each group on days 3, 5, and 7. (C) Clinical score for different groups. (D) Quantitative analysis of corneal thickness on day 7. Data presented as mean ± SEM (n = 6). *P < 0.05, **P < 0.01, ***P < 0.001.
Fig. 8.
Fig. 8.
(A) In vivo confocal microscopy images of the central and peripheral corneal stroma in eyes from separate groups on days 3, 5, and 7. Inflammatory cells are represented with orange arrows. (B) H&E staining and (C) Masson staining of different groups of corneal tissue sections.
Fig. 9.
Fig. 9.
(A) Immunofluorescence staining of fibronectin and CD11a (green) in corneas from different groups. Nuclei were stained with DAPI (blue). Quantitative analysis of (B) fibronectin and (C) CD11a intensity. Data presented as mean ± SEM (n = 5 to 6). *P < 0.05, **P < 0.01, ***P < 0.001.
Fig. 10.
Fig. 10.
Safety analysis of the formulations. (A) OCT images (cornea and retina) of eyes from different groups. (B) Fundus images from different groups. (C) Corneal thickness and (D) retina thickness did not differ between groups. Data presented as mean ± SEM (n = 5).
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Tuft S, Somerville TF, Li JO, Neal T, De S, Horsburgh MJ, Fothergill JL, Foulkes D, Kaye S. Bacterial keratitis: Identifying the areas of clinical uncertainty. Prog Retin Eye Res. 2022;89:101031. - PubMed
    1. Cabrera-Aguas M, Khoo P, Watson SL. Infectious keratitis: A review. Clin Experiment Ophthalmol. 2022;50(5):543–562. - PMC - PubMed
    1. Miller D, Cavuoto KM, Alfonso EC. Bacterial keratitis, in Infections of the cornea and conjunctiva. Singapore: Springer Singapore; 2021, p. 85–104.
    1. Austin A, Lietman T, Rose-Nussbaumer J. Update on the management of infectious keratitis. Ophthalmology. 2017;124(11):1678–1689. - PMC - PubMed
    1. Ting DSJ, Ho CS, Deshmukh R, Said DG, Dua HS. Infectious keratitis: An update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance. Eye (Lond). 2021;35(4):1084–1101. - PMC - PubMed

LinkOut - more resources