Development and Evaluation of a Novel Mucus Diffusion Test System Approved by Self-Nanoemulsifying Drug Delivery Systems

Friedl, Heike; Dünnhaupt, Sarah; Hintzen, Fabian; Waldner, Claudia; Parikh, Shruti; Pearson, Jeffrey P.; Wilcox, Matthew; Bernkop‐Schnürch, Andreas

doi:10.1002/jps.23757

Cited by 152 publications

(84 citation statements)

References 23 publications

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“…The membrane holder is placed between the two compartments containing the mucus separated between two drugpermeable membranes [19]. In contrast to the Side-by-Side® diffusion apparatus and the Transwell Snapwell system, a novel established method to study the diffusion in mucus is the Transwell diffusion system, a two compartment system [32]. A 24-well plate represents the acceptor compartment and additional 24 inserts the donor compartments, which are separated from each other by a membrane covered with 50 mg of fresh mucus as it is illustrated in Fig. 3.…”

Section: Transwell Diffusion Systemmentioning

confidence: 99%

“…Friedl et al have already established this system with self-emulsifying drug delivery systems (SNEDDS) within a sufficient experimental runtime over 4 hours [32]. They demonstrated that the particle size of nanoemulsion correlates with the permeation rate.…”

Section: Transwell Diffusion Systemmentioning

confidence: 99%

“…demonstrated a sufficient experimental runtime over 4 hours with a thin mucus layer [32]. In contrast, previous systems such as the three chamber Side-by-Side diffusion apparatus have long experimental durations of 15-20 hours owing to a comparatively large amount of mucus, fixed between donor and acceptor compartment [19,31].…”

Section: Transwell Diffusion Systemmentioning

confidence: 99%

“…Especially for high-priced drugs an decreased volume of the two compartments is convenient as in the Transwell® diffusion system only 250 µl test solution in the donor chamber and 500 µl buffer solution in the acceptor chamber are sufficient [32]. A smaller acceptor compartment offers the opportunity to test lower drug amounts without using high sensitive and expensive analytic apparatus.…”

Section: Transwell Diffusion Systemmentioning

confidence: 99%

See 3 more Smart Citations

Methods to determine the interactions of micro- and nanoparticles with mucus

Grießinger¹,

Dünnhaupt²,

Cattoz

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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Section: Transwell Diffusion Systemmentioning

confidence: 99%

Section: Transwell Diffusion Systemmentioning

confidence: 99%

Section: Transwell Diffusion Systemmentioning

confidence: 99%

Section: Transwell Diffusion Systemmentioning

confidence: 99%

See 2 more Smart Citations

Methods to determine the interactions of micro- and nanoparticles with mucus

Grießinger¹,

Dünnhaupt²,

Cattoz

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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“…In previous studies, it was shown that the model peptide leuprolide is protected against degradation by proteases after incorporation into SEDDS (Hintzen et al, 2014). In addition, certain SEDDS can also be attributed with mucus-permeating properties (Friedl et al, 2013) and stability toward pancreatic lipase (Mahjub et al, 2015). Taking this into consideration, SEDDS may also provide protection against presystemic inactivation of desmopressin.…”

Section: Introductionmentioning

confidence: 99%

Development andin vitroevaluation of an oral SEDDS for desmopressin

et al. 2016

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Context: Self-emulsifying drug delivery systems (SEDDS) are among most promising tools for improving oral peptide bioavailability. Objective: In this study, in vitro protective effect of SEDDS containing desmopressin against presystemic inactivation by glutathione and a-chymotrypsin was evaluated. Materials and methods: The partitioning coefficient (log P) of desmopressin was increased via hydrophobic ion pairing using anionic surfactants. Solubility studies were performed to select the appropriate solvents for SEDDS preparation. Subsequently, droplet size and emulsification properties of 22 SEDDS formulations were evaluated. Moreover, the peptide-surfactant complex was dissolved in two chosen SEDDS formulations. Finally, SEDDS containing desmopressin were characterized regarding lipase stability, toxicity, and in vitro protective effect toward glutathione and a-chymotrypsin. Results: Desmopressin log P was increased from initial À6.13 to 0.33 using sodium docusate. The resulting desmopressin docusate complex (DES/AOT) was incorporated in two different SEDDS formulations, containing Capmul 907 P as main solvent. DES/AOT-SEDDS-F4 (containing 0.07% w/w DES/AOT) was composed of 50% Capmul 907P, 40% Cremophor RH40, and 10% Transcutol. The comparatively more hydrophilic formulation DES/AOT-SEDDS-F15 (containing 0.25% w/w DES/AOT) consisted of 20% Capmul 907P, 40% Acconon MC8-2, and 40% Tween 20. Both formulations were stable toward digestion by lipase and protected desmopressin toward a-chymotrypsin degradation. Moreover, DES/AOT-SEDDS-F4 also protected the peptide from thiol/disulfide exchange reactions with glutathione and was not cytotoxic at a concentration of 0.375% (w/w). Conclusion: DES/AOT-SEDDS-F4 protected desmopressin from in vitro glutathione and a-chymotrypsin degradation. DES/AOT-SEDDS-F4 was metabolically stable and nontoxic. Therefore, it could be considered as a potential delivery system for oral desmopressin administration.

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Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix

Tomasetti

Breunig

2017

Adv Healthcare Materials

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Although nanosized drug delivery systems are promising tools for the treatment of severe diseases, the extracellular matrix (ECM) constitutes a major obstacle that endangers therapeutic success. Mobility of diffusing species is restricted not only by small pore size (down to as low as 3 nm) but also by electrostatic interactions with the network. This article evaluates commonly used in vitro models of ECM, analytical methods, and particle types with respect to their similarity to native conditions in the target tissue. In this cross-study evaluation, results from a wide variety of mobility studies are analyzed to discern general principles of particle-ECM interactions. For instance, cross-linked networks and a negative network charge are essential to reliably recapitulate key features of the native ECM. Commonly used ECM mimics comprised of one or two components can lead to mobility calculations which have low fidelity to in vivo results. In addition, analytical methods must be tailored to the properties of both the matrix and the diffusing species to deliver accurate results. Finally, nanoparticles must be sufficiently small to penetrate the matrix pores (ideally R < 0.5; d = particle diameter, p = pore size) and carry a neutral surface charge to avoid obstructions. Larger (R >> 1) or positively charged particles are trapped.

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Development and Evaluation of a Novel Mucus Diffusion Test System Approved by Self-Nanoemulsifying Drug Delivery Systems

Cited by 152 publications

References 23 publications

Methods to determine the interactions of micro- and nanoparticles with mucus

Methods to determine the interactions of micro- and nanoparticles with mucus

Development andin vitroevaluation of an oral SEDDS for desmopressin

Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix

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