Development, in vitro and in vivo evaluation of a self-emulsifying drug delivery system (SEDDS) for oral enoxaparin administration

Zupančič, Ožbej; Grieβinger, Julia Anita; Rohrer, Julia; Sousa, Irene Pereira de; Danninger, Lukas; Partenhauser, Alexandra; Sündermann, Nadine Elli; Laffleur, Flavia; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ejpb.2016.09.013

Cited by 78 publications

(33 citation statements)

References 38 publications

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“…Moreover, SEDDS can pass the mucus gel barrier in a comparatively more efficient manner (8) and are known for their permeation enhancing properties (9). So far, promising in vivo results could be obtained by hydrophobic ion pairing of the peptide leuprolide (4) and of the low molecular weight heparin enoxaparin (10) being incorporated into SEDDS. In case of leuprolide an even 17.2-fold increase in oral bioavailability in rats compared to an aqueous solution was achieved (4).…”

Section: Introductionmentioning

confidence: 99%

Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs

Bonengel

Jelkmann

Abdulkarim

et al. 2018

Journal of Controlled Release

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Section: Introductionmentioning

confidence: 99%

Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs

Bonengel

Jelkmann

Abdulkarim

et al. 2018

Journal of Controlled Release

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“…Via hydrophobic ion pairing with cationic surfactants, however, even hydrophilic macromolecular drugs such as peptides, heparins and DNA/RNA‐based drugs can be incorporated in SEDDS. Daptomycin and enoxaparin, for example, were ion‐paired with dodecylamine hydrochloride, cetrimonium bromide and benzalkonium chloride and then successfully incorporated into SEDDS for oral delivery . DNA/RNA‐based drugs are similar to peptide drugs regarding their hydrophilicity and sensibility to enzymatic degradation.…”

Section: Introductionmentioning

confidence: 99%

“…Daptomycin and enoxaparin, for example, were ion-paired with dodecylamine hydrochloride, cetrimonium bromide and benzalkonium chloride and then successfully incorporated into SEDDS for oral delivery. [3,4] DNA/RNA-based drugs are similar to peptide drugs regarding their hydrophilicity and sensibility to enzymatic degradation. Therefore, hydrophobically ion-paired complexes of pDNA were also studied for oral delivery via SEDDS.…”

Section: Introductionmentioning

confidence: 99%

Self-emulsifying drug delivery systems and cationic surfactants: do they potentiate each other in cytotoxicity?

Lam

Le‐Vinh

Phan³

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives The aim of this study was to evaluate the cytotoxicity of self‐emulsifying drug delivery systems (SEDDS) containing five different cationic surfactants. Methods Cationic surfactants were added in a concentration of 1% and 5% (m/m) to SEDDS comprising 30% Capmul MCM, 30% Captex 355, 30% Cremophor EL and 10% propylene glycol. The resulting formulations were characterized in terms of size, zeta potential, in‐vitro haemolytic activity and toxicity on Caco‐2 via MTT assay and lactate dehydrogenase release assay. Key findings The evaluated surfactants had in both concentrations a minor impact on the size of SEDDS ranging from 30.2 ± 0.6 to 55.4 ± 1.1 nm, whereas zeta potential changed significantly from −9.0 ± 0.3 to +28.8 ± 1.6 mV. The overall cytotoxicity of cationic surfactants followed the rank order: hexadecylpyridinium chloride > benzalkonium chloride > alkyltrimethylammonium bromide > octylamine > 1‐decyl‐3‐methylimidazolium. The haemolytic activity of the combination of cationic surfactants and SEDDS on human red blood cells was synergistic. Furthermore, cationic SEDDS exhibited higher cytotoxicity of Caco‐2 cells compared to SEDDS without cationic surfactants. Conclusions According to these results, SEDDS and cationic surfactants seem to bear an additive up to synergistic toxic risk.

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“…In order to do so, first a cell viability test was performed. The resazurin assay showed a notable reduction of cell viability after an incubation time of 6 h. This can be explained by the relatively high concentration of the 1% (v/v) SEDDS emulsion, as it is known that surfactants show toxic effects at higher concentrations (18,19). The concentration of a SEDDS emulsion needed for drug delivery is expected to be much lower and thus the toxic profile of the highly concentrated SEDDS emulsion is not considered an issue.…”

Section: Discussionmentioning

confidence: 96%

Development and In Vitro Evaluation of Stearic Acid Phosphotyrosine Amide as New Excipient for Zeta Potential Changing Self-Emulsifying Drug Delivery Systems

et al. 2020

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PURPOSEDevelopment of zeta potential changing SEDDS containing newly synthesized derivative stearic acid phosphotyrosine amide. METHODSStearoyl chloride was conjugated with phosphotyrosine, which is substrate for the brush border enzyme intestinal alkaline phosphate. The synthesized derivative was implemented in different SEDDS formulations and the zeta potential changing properties and the concluding mucus diffusion abilities were evaluated. RESULTSStearic acid phosphotyrosine amide was successfully synthesized and incorporated into SEDDS. A SEDDS formulation containing the new derivative showed a zeta potential of −14 mV before, and + 2 mV after enzymatic cleavage by intestinal alkaline phosphatase. Experiments on a Caco-2 monolayer demonstrated that the phosphate cannot only be cleaved by isolated enzyme, but also by enzyme, which was expressed by cells. The mucus diffusion abilities of the untreated, negatively charged SEDDS were significantly higher compared to the enzymatically cleaved, positively charged SEDDS. CONCLUSIONThe developed stearic acid phosphotyrosine represents a promising excipient for zeta potential changing SEDDS. KEYWORDSSEDDS . zeta potential changing drug delivery systems . phosphotyrosine . phosphatase ABBREVIATIONS DMSO Dimethyl sulfoxide FDA Fluorescein diacetate GIT Gastrointestinal tract HBS HEPES-buffered Saline IAP Intestinal alkaline phosphatase MEM Minimum essential medium PBS Phosphate-buffered saline PTyr Phosphotyrosine SA-PTyr Stearic acid phosphotyrosine amide SEDDS Self-emulsifying drug delivery system

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Development, in vitro and in vivo evaluation of a self-emulsifying drug delivery system (SEDDS) for oral enoxaparin administration

Cited by 78 publications

References 38 publications

Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs

Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs

Self-emulsifying drug delivery systems and cationic surfactants: do they potentiate each other in cytotoxicity?

Development and In Vitro Evaluation of Stearic Acid Phosphotyrosine Amide as New Excipient for Zeta Potential Changing Self-Emulsifying Drug Delivery Systems

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