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Wallenwein, Chantal M.; Ashtikar, Mukul; Hofhaus, Götz; Haferland, Isabel; Thurn, Manuela; König, Anke; Pinter, Andreas; Dressman, Jennifer; Wacker, Matthias G.
International journal of pharmaceutics, 02/2023, Letnik: 633Journal Article
Display omitted Chronic wounds often contain high levels of proinflammatory cytokines that prolong the wound-healing process. Patients suffering from these conditions are likely to benefit from topical rifampicin therapy. Although recent research indicates considerable anti-inflammatory properties of the antibiotic, currently, there are no commercial topical wound healing products available. To address this medical need, a liposomal drug delivery system was developed. A mechanistic investigation outlined major influences of wound environments that affect the release kinetics and, as a consequence, local bioavailability. Liposomes were prepared using the thin-film hydration method and subsequently freeze-dried at the pilot scale to improve their stability. We investigated the influence of oxidation, plasma proteins, and lipolysis on the in vitro release of rifampicin and its two main degradation products using the Dispersion Releaser technology. A novel simulated wound fluid provided a standardized environment to study critical influences on the release. It reflects the pathophysiological environment regarding pH, buffer capacity, and protein content. During storage, the liposomes efficiently protect rifampicin from degradation. After the dispersion of the vesicles in simulated wound fluid, despite the significant albumin binding (>70%), proteins have no considerable effect on the release. Also, the presence of lipase at pathophysiologically elevated concentrations did not trigger the liberation of rifampicin. Surprisingly, the oxidative environment of the wound bed represents the strongest accelerating influence and triggers the release. A stable topical delivery system of rifampicin has been developed. Once the formulation comes in contact with simulated wound fluid, drug oxidation accelerates the release. The influence of lipases that are assumed to trigger the liberation from liposomes depends on the drug-to-lipid ratio. Considering that inflamed tissues exhibit elevated levels of oxidative stress, the trigger mechanism identified for rifampicin contributes to targeted drug delivery.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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