Bioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by <i>Salmonella enterica</i>

Menina, Sara; Eisenbeis, Janina; Kamal, Mohamed Ashraf M.; Koch, Marcus; Bischoff, Markus; Gordon, Sarah; Loretz, Brigitta; Lehr, Claus‐Michael

doi:10.1002/adhm.201900564

Cited by 50 publications

(37 citation statements)

References 93 publications

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“…Subsequently, cells were fixed with 3.7 % (v/v) paraformaldehyde for 20 min at room temperature (RT). Nucleus staining was performed using a 1 µg/mL 4′,6-Diamidino-2-phenylindole dihydrochloride (DAPI) (Sigma Aldrich) solution (32). For confocal imaging (Leica TCS SB8) a 488 nm laser was used to visualise fluorescein, a 405 nm laser for DAPI and a 561 nm laser for DiI.…”

Section: Confocal Imagingmentioning

confidence: 99%

Hot EVs – How temperature affects extracellular vesicles

Schulz

Karagianni

Koch

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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In recent years, extracellular vesicles (EVs) and outer membrane vesicles (OMVs) have become an extensive and diverse field of research. They hold potential as diagnostic markers, therapeutics and for fundamental biological understanding. Despite ongoing studies, numerous information regarding function, content and stability of EVs remains unclear. If EVs and OMVs ought to be used as therapeutics and in clinical environments, their stability is one of the most important factors to be considered. Especially for formulation development, EVs and OMVs need to be stable at higher temperatures. To the best of our knowledge, very little work has been published regarding heat stability of neither EVs nor OMVs. In the present study, we investigated B lymphoblastoid cellderived EVs and OMVs derived from myxobacterial species Sorangiineae as model vesicles. We exposed the vesicles to 37 °C, 50 °C, 70 °C and 100 °C for 1 h, 6 h and 24 h, and also autoclaved them. Physico-chemical analysis such as size, particle concentration and protein concentration showed interestingly minor alterations, particularly at 37 °C. Flow cytometry analysis emphasised these results suggesting that after heat impact, EVs and OMVs were still able to be taken up by macrophage-like dTHP-1 cells. These data indicate that both mammalian and bacterial vesicles show intrinsic stability at physiological temperature. Our findings are important to consider for vesicle formulation and for advanced bioengineering approaches.

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Section: Confocal Imagingmentioning

confidence: 99%

Hot EVs – How temperature affects extracellular vesicles

Schulz

Karagianni

Koch

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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“…The positively charged colistin contains a lipophilic moiety and could interact with aSq molecules via both charged and hydrophobic interactions (Yasar et al, 2018;Menina et al, 2019). We, thus, hypothesized that the solvent evaporation method could enhance the LC and EE of colistin in aSq-NPs.…”

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confidence: 99%

Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform

Christmann

Murgia

et al. 2020

Front. Chem.

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Limited drug loading capacity (LC), mostly below 5% w/w, is a significant drawback of nanoparticulate drug delivery systems (DDS). Squalenoylation technology, which employs bioconjugation of squalenyl moiety and drug, allows self-assemble of nanoparticles (NPs) in aqueous media with significantly high LC (>30% w/w). The synthesis and particle preparation of squalenoylated prodrugs are, however, not facile for molecules with multiple reactive groups. Taking a different approach, we describe the synthesis of amphiphilic squalenyl derivatives (SqDs) as well as the physicochemical and biopharmaceutical characterizations of their self-assembled NPs as DDSs. The SqDs included in this study are (i) cationic squalenyl diethanolamine (ii) PEGylated SqD (PEG 750 Da), (iii) PEGylated SqD (PEG 3,000 Da), and (iv) anionic squalenyl hydrogen sulfate. All four SqDs self-assemble into NPs in a size range from 100 to 200 nm in an aqueous solution. Furthermore, all NP derivatives demonstrate appropriate biocompatibility and adequate colloidal stability in physiological relevant pH environments. The mucoprotein binding of PEGylated NPs is reduced compared to the charged NPs. Most importantly, this technology allows excellent LC (at maximum of 45% w/w) of a wide range of multifunctional compounds, varying in physicochemical properties and molecular weight. Interestingly, the drug release profile can be tuned by different loading methods. In summary, the SqD-based NPs appear as versatile drug delivery platforms.

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“…136,137 Furthermore, encapsulation of colistin, an otherwise poorly permeable compound, into liposomes coated with the extracellular adherence protein (Eap) of Staphylococcus aureus facilitated intracellular drug delivery and resulted in a significant reduction of bacterial load in Salmonella enterica infected Caco-2 cell transwell cultures. 138…”

Section: Disease-modelingmentioning

confidence: 99%

The Past, Present and Future of Intestinal In Vitro Cell Systems for Drug Absorption Studies

Youhanna

Lauschke

2021

Journal of Pharmaceutical Sciences

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The intestinal epithelium acts as a selective barrier for the absorption of water, nutrients and orally administered drugs. To evaluate the gastrointestinal permeability of a candidate molecule, scientists and drug developers have a multitude of cell culture models at their disposal. Static transwell cultures constitute the most extensively characterized intestinal in vitro system and can accurately categorize molecules into low, intermediate and high permeability compounds. However, they lack key aspects of intestinal physiology, including the cellular complexity of the intestinal epithelium, flow, mechanical strain, or interactions with intestinal mucus and microbes. To emulate these features, a variety of different culture paradigms, including microfluidic chips, organoids and intestinal slice cultures have been developed. Here, we provide an updated overview of intestinal in vitro cell culture systems and critically review their suitability for drug absorption studies. The available data show that these advanced culture models offer impressive possibilities for emulating intestinal complexity. However, there is a paucity of systematic absorption studies and benchmarking data and it remains unclear whether the increase in model complexity and costs translates into improved drug permeability predictions. In the absence of such data, conventional static transwell cultures remain the current gold-standard paradigm for drug absorption studies.

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Bioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by Salmonella enterica

Cited by 50 publications

References 93 publications

Hot EVs – How temperature affects extracellular vesicles

Hot EVs – How temperature affects extracellular vesicles

Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform

The Past, Present and Future of Intestinal In Vitro Cell Systems for Drug Absorption Studies

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