How wound environments trigger the release from Rifampicin-loaded liposomes

Wallenwein, Chantal M.; Ashtikar, Mukul; Hofhaus, Götz; Haferland, Isabel; Thurn, Manuela; König, Anke; Pinter, Andreas; Dressman, Jennifer B.; Wacker, Matthias G.

doi:10.1016/j.ijpharm.2023.122606

Cited by 5 publications

(4 citation statements)

References 61 publications

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“…Approximately 80% of the drug was released within the first two hours. Ascorbic acid is an antioxidant and inhibits the oxidation of rifabutin, a common process observed for other rifamycin derivatives as well [16,17]. 2 (right).…”

Section: Nanoparticle Characteristicsmentioning

confidence: 92%

Comparison of Compartmental and Non-Compartmental Analysis to Detect Biopharmaceutical Similarity of Intravenous Nanomaterial-Based Rifabutin Formulations

Osipova

Budko²,

Maksimenko

et al. 2023

Pharmaceutics

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Pharmacometric analysis is often used to quantify the differences and similarities between formulation prototypes. In the regulatory framework, it plays a significant role in the evaluation of bioequivalence. While non-compartmental analysis provides an unbiased data evaluation, mechanistic compartmental models such as the physiologically-based nanocarrier biopharmaceutics model promise improved sensitivity and resolution for the underlying causes of inequivalence. In the present investigation, both techniques were applied to two nanomaterial-based formulations for intravenous injection, namely, albumin-stabilized rifabutin nanoparticles and rifabutin-loaded PLGA nanoparticles. The antibiotic rifabutin holds great potential for the treatment of severe and acute infections of patients co-infected with human immunodeficiency virus and tuberculosis. The formulations differ significantly in their formulation and material attributes, resulting in an altered biodistribution pattern as confirmed in a biodistribution study in rats. The albumin-stabilized delivery system further undergoes a dose-dependent change in particle size which leads to a small yet significant change in the in vivo performance. A second analysis was conducted comparing the dose fraction-scaled pharmacokinetic profiles of three dose levels of albumin-stabilized rifabutin nanoparticles. The dose strength affects both the nanomaterial-related absorption and biodistribution of the carrier as well as the drug-related distribution and elimination parameters, increasing the background noise and difficulty of detecting inequivalence. Depending on the pharmacokinetic parameter (e.g., AUC, Cmax, Clobs), the relative (percentage) difference from the average observed using non-compartmental modeling ranged from 85% to 5.2%. A change in the formulation type (PLGA nanoparticles vs. albumin-stabilized rifabutin nanoparticles) resulted in a similar level of inequivalence as compared to a change in the dose strength. A mechanistic compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model led to an average difference of 152.46% between the two formulation prototypes. Albumin-stabilized rifabutin nanoparticles tested at different dose levels led to a 128.30% difference, potentially due to changes in particle size. A comparison of different dose strengths of PLGA nanoparticles, on average, led to a 3.87% difference. This study impressively illustrates the superior sensitivity of mechanistic compartmental analysis when dealing with nanomedicines.

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Section: Nanoparticle Characteristicsmentioning

confidence: 92%

Comparison of Compartmental and Non-Compartmental Analysis to Detect Biopharmaceutical Similarity of Intravenous Nanomaterial-Based Rifabutin Formulations

Osipova

Budko²,

Maksimenko

et al. 2023

Pharmaceutics

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“…Rifampicin-loaded liposomes were manufactured using the thin lipid film hydration method [42]. A more detailed description of the preparation of the liposomes was reported previously [15]. Briefly, Lipoid S100 (≥94% of phosphatidylcholine) and rifampicin were dissolved in methanol which was then evaporated using a rotary evaporator (Büchi Ro-tavapor R-114, Büchi Labortechnik AG, Flawil, Schweiz).…”

Section: Preparation Of the Liposomes Incorporation Into Hydrogels An...mentioning

confidence: 99%

“…Earlier, we developed a new simulated wound fluid (SWF), which was used as the release medium for all experiments. SWF reflects the physiological conditions of wounds in terms of pH, buffer capacity, and protein content [15]. In addition, 1% [v/v] of a PenStrep ® solution was added to avoid microbial contamination, and media were deaerated by heating them to approximately 41 • C and stirring gently under a vacuum for 30 min (USP conditions).…”

Section: In Vitro Release Studies Using the Dispersion Releaser Techn...mentioning

confidence: 99%

“…RQ represents the main degradation product, while hydrolysis to 3-FR is accelerated in an acidic environment [13,14]. While previous investigations were focused on the encapsulation of rifampicin into liposomes [15], the current study emphasizes the development of two nanostructured hydrogel formulations. They enable the topical administration of rifampicin, prolong the residence time of the drug, and enhance penetration into the wound bed.…”

Section: Introductionmentioning

confidence: 99%

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Pharmaceutical Development of Nanostructured Vesicular Hydrogel Formulations of Rifampicin for Wound Healing

Wallenwein

Weigel

Hofhaus

et al. 2022

IJMS

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Chronic wounds exhibit elevated levels of inflammatory cytokines, resulting in the release of proteolytic enzymes which delay wound-healing processes. In recent years, rifampicin has gained significant attention in the treatment of chronic wounds due to an interesting combination of antibacterial and anti-inflammatory effects. Unfortunately, rifampicin is sensitive to hydrolysis and oxidation. As a result, no topical drug product for wound-healing applications has been approved. To address this medical need two nanostructured hydrogel formulations of rifampicin were developed. The liposomal vesicles were embedded into hydroxypropyl methylcellulose (HPMC) gel or a combination of hyaluronic acid and marine collagen. To protect rifampicin from degradation in aqueous environments, a freeze-drying method was developed. Before freeze-drying, two well-defined hydrogel preparations were obtained. After freeze-drying, the visual appearance, chemical stability, residual moisture content, and redispersion time of both preparations were within acceptable limits. However, the morphological characterization revealed an increase in the vesicle size for collagen–hyaluronic acid hydrogel. This was confirmed by subsequent release studies. Interactions of marine collagen with phosphatidylcholine were held responsible for this effect. The HPMC hydrogel formulation remained stable over 6 months of storage. Moving forward, this product fulfills all criteria to be evaluated in preclinical and clinical studies.

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From in vitro to in vivo: A comprehensive guide to IVIVC development for long-acting therapeutics

Venkatesan

Benetti

Wacker

2023

Advanced Drug Delivery Reviews

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How wound environments trigger the release from Rifampicin-loaded liposomes

Cited by 5 publications

References 61 publications

Comparison of Compartmental and Non-Compartmental Analysis to Detect Biopharmaceutical Similarity of Intravenous Nanomaterial-Based Rifabutin Formulations

Comparison of Compartmental and Non-Compartmental Analysis to Detect Biopharmaceutical Similarity of Intravenous Nanomaterial-Based Rifabutin Formulations

Pharmaceutical Development of Nanostructured Vesicular Hydrogel Formulations of Rifampicin for Wound Healing

From in vitro to in vivo: A comprehensive guide to IVIVC development for long-acting therapeutics

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