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Mucoadhesive Emulsion Microgels for Intravesical Drug Delivery: Preparation, Retention at Urothelium, and Biodistribution Study

Cite this: ACS Appl. Mater. Interfaces 2023, 15, 21, 25354–25368
Publication Date (Web):May 19, 2023
https://doi.org/10.1021/acsami.3c02741
Copyright © 2023 American Chemical Society

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    The intravesical instillation procedure is a proven method in modern urology for the treatment of bladder diseases. However, the low therapeutic efficiency and painfulness of the instillation procedure are significant limitations of this method. In the present study, we propose an approach to solving this problem by using microsized mucoadhesive macromolecular carriers based on whey protein isolate with the possibility of prolonged release of drugs as a drug delivery system. The optimal water-to-oil ratio (1:3) and whey protein isolate concentration (5%) were determined to obtain emulsion microgels with sufficient loading efficiency and mucoadhesive properties. The droplet diameter of emulsion microgels varies from 2.2 to 3.8 μm. The drug release kinetics from the emulsion microgels was evaluated. The release of the model dye in saline and artificial urine in vitro was observed for 96 h and reached up to 70% of loaded cargo for samples. The effect of emulsion microgels on the morphology and viability of two cell lines was observed: L929 mouse fibroblasts (normal adherent cells) and THP-1 human monocytes (cancer suspension cells). Developed emulsion microgels (5%, 1:3 and 1:5) showed sufficient mucoadhesion to a porcine bladder urothelium ex vivo. The biodistribution of emulsion microgels (5%, 1:3 and 1:5) in mice (n = 3) after intravesical (instillation) and systemic (intravenous) administration was assessed in vivo and ex vivo using near-infrared fluorescence live imaging for real time. It was demonstrated that intravesical instillation allows approximately 10 times more efficient accumulation of emulsion microgels in the mice urinary bladder in vivo 1 h after injection compared to systemic injection. The retention of the emulsion of mucoadhesive microgels in bladders after the intravesical instillation was observed for 24 h.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsami.3c02741.

    • Table S-1 listing average sizes, ζ-potentials, and conductivities of droplets in emulsion microgels; Figure S-1 showing CLSM images of L929 and THP-1 control cells and cells incubated with the (2.5%, 1:3) and (7.5%, 1:3) emulsion microgels for 3, 6, and 24 h, and MTT L929 cell viability studies after their incubation with the (2.5%, 1:3) and (7.5%, 1:3) emulsion microgels with various ratios; Figure S-2 showing optical images of L929 and THP-1 control cells and cells incubated with the emulsion microgels for 3, 6, and 24 h; Figure S-3 showing optical fluorescent images of the urothelium surface of porcine bladder after their incubation with emulsion microgels samples and after their washings with artificial urine; Figure S-4 showing intravital bioimaging of the fluorescent dye cyanine 7-stained emulsion microgels with different oil content; Figure S-5 showing CLSM images demonstrating overview of urinary bladder tissue cryosections and the localization of emulsion microgels in the tissue in 1 and 5 h after intravesical instillation of microgels (PDF)

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    Cited By

    This article is cited by 1 publications.

    1. Fayang Li, Xianhuang Chen, Yuanqiao He, Zhiping Peng. Mucoadhesive Thiolated Hyaluronic Acid/Pluronic F127 Nanogel Formation via Thiol–Maleimide Click Reaction for Intravesical Drug Delivery. ACS Applied Bio Materials 2024, 7 (3) , 1976-1989. https://doi.org/10.1021/acsabm.4c00068