Comparison of the protective effect of self-emulsifying peptide drug delivery systems towards intestinal proteases and glutathione

Hetényi, Gergely; Griesser, Janine; Moser, Michael T.; Demarne, Frédéric; Jannin, Vincent; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ijpharm.2017.03.027

Cited by 67 publications

(20 citation statements)

References 20 publications

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“…Belonging to the group of lipid-based formulations, SEDDS can help overcome the main reasons for low oral absorption of peptide drugs, namely enzymatic degradation by intestinal proteases, poor mucus permeating properties and low cellular uptake. For example, it has been already proven, that hydrolyzing enzymes such as pepsin, trypsin, chymotrypsin and elastase are not soluble in the oily SEDDS droplets and that therapeutic peptides incorporated in SEDDS are therefore protected against enzymatic degradation [6]. Further,, SEDDS bear a slippery surface facilitating mucus permeation even for large molecules [7].…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide

Menzel

Holzeisen

Laffleur

et al. 2018

Journal of Controlled Release

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Section: Introductionmentioning

confidence: 99%

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide

Menzel

Holzeisen

Laffleur

et al. 2018

Journal of Controlled Release

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“…Despite the advances in peptide and protein delivery, the oral delivery of GLP-1 analogues like exenatide is still an elusive goal being limited by mainly the enzymatic barrier, mucus barrier and low membrane permeability. In this study, exenatide was incorporated in lipid-based NCs since it has been proven in many previous studies that lipid-based NCs can overcome the above mentioned hurdles for oral peptide delivery [7,16,22]. Hydrophobic ion pairing was applied before incorporation in NCs to sufficiently reduce hydrophilicity of the peptide by masking its ionic substructures with bulky lipophilic counter-ions [17,21,31].…”

Section: Discussionmentioning

confidence: 99%

“…Because of a limited stability of HIPs in the GI tract, the incorporation of HIPs into lipophilic carrier systems is advantageous [13][14][15]. In addition to a protective effect towards presystemic metabolism [16][17][18], lipid-based nanocarrier systems in particular proved to be able to facilitate mucus T permeation and to enhance the cellular uptake of peptides [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

Ismail

Phan

Laffleur

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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The lipophilic character of peptides can be tremendously improved by hydrophobic ion pairing (HIP) with counterions to be efficiently incorporated into lipid-based nanocarriers (NCs). Herein, HIPs of exenatide with the cationic surfactant tetraheptylammonium bromide (THA) and the anionic surfactant sodium docusate (DOC) were formed to increase its lipophilicity. These HIPs were incorporated into lipid based NCs comprising 41% Capmul MCM, 15% Captex 355, 40% Cremophor RH and 4% propylene glycol. Exenatide-THA NCs showed a log D lipophilic phase (LPh)/release medium (RM) of 2.29 and 1.92, whereas the log D LPh/RM of exenatide-DOC was 1.2 and −0.9 in simulated intestinal fluid and Hanks' balanced salts buffer (HBSS), respectively. No significant hemolytic activity was induced at a concentration of 0.25% (m/v) of both blank and loaded NCs. Exenatide-THA NCs and exenatide-DOC NCs showed a 10-fold and 3-fold enhancement in intestinal apparent membrane permeability compared to free exenatide, respectively. Furthermore, orally administered exenatide-THA and exenatide-DOC NCs in healthy rats resulted in a relative bioavailability of 27.96 ± 5.24% and 16.29 ± 6.63%, respectively, confirming the comparatively higher potential of the cationic surfactant over the anionic surfactant. Findings of this work highlight the potential of the type of counterion used for HIP as key to successful design of lipid-based NCs for oral exenatide delivery.

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“…Beside the main use of SEDDS for the delivery of hydrophobic agents, recently, this system was explored as a carrier for orally administered hydrophilic macromolecules which are prone to intestinal enzymatic degradation. To be loaded into the oil phase, these hydrophilic agents are turned into hydrophobic agents through a technique known as the Hydrophobic Ionic Paring technique (HIP) [105]. This HIP technique includes the pairing of peptides with a macromolecular hydrophobic counter ion which turns the peptides into hydrophobic agents with high oil solubility.…”

Section: Sedds For Delivery Of Hydrophilic/lipophilic Agentsmentioning

confidence: 99%

Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies

Abdulkarim

Sharma

Gumbleton

2019

Advanced Drug Delivery Reviews

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Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends to include therapeutic macromolecules and nanoparticles (NPs) through trapping of these particles. Mucus is not only a physical barrier that limiting particles movements based on their sizes but it selectively binds with particles through both hydrophilic and lipophilic interactions. Therefore, nano-carriers for mucosal delivery should be designed to eliminate entrapment by the mucus barrier. For this reason, different strategies have been approached for both solid nano-carriers and liquid core nano-carriers to synthesise muco-diffusive nano-carrier. Among these nano-strategies, Self-Emulsifying Drug Delivery System (SEDDS) was recognised as very promising nano-carrier for mucus delivery. The system was introduced to enhance the dissolution and bioavailability of orally administered insoluble drugs. SEDDS has shown high stability against intestinal enzymatic activity and more importantly, relatively rapid permeation characteristics across mucus barrier. The high diffusivity of SEDDS has been tested using various in vitro measurement techniques including both bulk and individual measurement of droplets diffusion within mucus. The selection and processing of an optimum in vitro technique is of great importance to avoid misinterpretation of the diffusivity of SEDDS through mucus barrier. In conclusion, SEDDS is a system with high capacity to diffuse through intestinal mucus even though this system has not been studied to the same extent as solid nano-carriers.

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Comparison of the protective effect of self-emulsifying peptide drug delivery systems towards intestinal proteases and glutathione

Cited by 67 publications

References 20 publications

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies

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