14th Hellenic Polymer Society International Conference
22-25 November, 2023, Thessaloniki, Greece

Invited lecture: Thiolated Polymers – Thiomers: Utilizing the most prominent bridging structure designed by nature

Prof. Dr. A. Bernkop-Schnürch
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2nd Edition International Conference on Nanotechnology & Materials Science
Conference
September 23-25, 2024
Paris, France

Invited lecture:
Thiolated Nanocarriers for Drug Delivery: Mimicking the Workhorses of Our Body

Prof. Dr. A. Bernkop-Schnürch
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Self-Emulsifying Drug Delivery Systems

Self-emulsifying drug delivery systems are simply oily drug solutions that can be administered in many forms such as capsules or liquids forming oily droplets preferably in the size between 25 and 300 nm once getting into contact with body fluids. As illustrated in Figure 1 even hydrophilic macromolecular drugs such as therapeutic peptides [Griesser J., Hetényi G., Moser M., Demarne F., Jannin V., Bernkop-Schnürch A. (2017) Hydrophobic ion pairing: Key to highly payloaded self-emulsifying peptide drug delivery systems. Int. J. Pharm., 520, 267-274; Hintzen F., Perera G., Hauptstein S., Müller C., Laffleur F., Bernkop-Schnürch A. (2014)  In vivo evaluation of an oral self-microemulsifying drug delivery system (SMEDDS) for leuprorelin.  Int. J. Pharm., 472, 20-6], DNA/RNA-based drugs [Hauptstein S., Prüfert F., Bernkop-Schnürch A. (2015) Self-nanoemulsifying drug delivery systems as novel approach for pDNA drug delivery.  Int. J. Pharm., 487, 25-31] or heparins [Zupančič O., Grieβinger J.A., Rohrer J., Pereira de Sousa I., Danninger L., Partenhauser A., Sündermann N.E., Laffleur F., Bernkop-Schnürch A. (2016) Development, in vitro and in vivo evaluation of a self-emulsifying drug delivery system (SEDDS) for oral enoxaparin administration. Eur. J. Pharm. Biopharm., 109, 113-121] can be incorporated in these oily solutions via hydrophobic ion pairing.

Fig. 1. Illustration of SEDDS containing biologics that are incorporated in the lipophilic phase via hydrophobic ion pairing with appropriate surfactants

Protective effect towards a presystemic metabolism
As enzymes being responsible for a presystemic metabolism of drugs such as peptidases or nucleases cannot diffuse into the oily droplets, they are protected towards them. In addition, thiol/disulphide exchange reactions of therapeutic peptides and proteins with endogenous glutathione and thiols of nutritive proteins can be excluded [Suchaoin W., Bernkop-Schnürch A. (2017) Nanocarriers protecting toward an intestinal pre-uptake metabolism. Nanomedicine (Lond), 12, 255-269].

High mucus permeating properties
The oily droplets formed by SEDDS are among the highest mucus permeating nanocarrier systems. Due to the incorporation of surfactants exhibiting PEG substructures such as Cremophors these mucus permeating properties can be even further improved [Friedl H., Dünnhaupt S., Hintzen F., Waldner C., Parikh S., Pearson J.P., Wilcox M.D., Bernkop-Schnürch A. (2013) Development and evaluation of a novel mucus diffusion test system approved by self-nanoemulsifying drug delivery systems. J. Pharm. Sci., 102, 4406-13], as the PEG assembles on the surface of the droplets making them more slippery. 

High mucoadhesive properties
Due to the incorporation of mucoadhesive polymers such as chitosans or polyacrylates, oily droplets formed by SEDDS can be made highly mucoadhesive [Efiana N.A., Mahmood A., Lam H.T., Zupančič O., Leonaviciute G., Bernkop-Schnürch A. (2017) Improved mucoadhesive properties of self-nanoemulsifying drug delivery systems (SNEDDS) by introducing acyl chitosan. Int. J. Pharm., 519, 206-212].

High spreading properties on the mucosa
For many applications a fast and efficient spreading of the drug over the target mucosa is essential. Formulated in the right way, the oily droplets of SEDDS can provide this feature to a comparatively high extent [Köllner et al. (2017) Self-emulsifiying drug delivery systems: Design of a novel vaginal delivery system for curcumin. Eur. J.  Pharm. Biopharm., in press].

Permeation enhancing properties
In numerous studies SEDDS were shown to exhibit high permeation enhancing properties [Leonaviciute G., Bernkop-Schnürch A. (2015) Self-emulsifying drug delivery systems in oral (poly)peptide drug delivery. Expert Opin. Drug Deliv., 12, 1703-16]. Furthermore, they were shown to strongly improve the uptake of DNA-based drugs into cells [Mahmood A., Prüfert F., Efiana N.A., Ashraf M.I., Hermann M., Hussain S., Bernkop-Schnürch A. (2016) Cell-penetrating self-nanoemulsifying drug delivery systems (SNEDDS) for oral gene delivery. Expert Opin. Drug Deliv., 13, 1503-1512].

A. Bernkop-Schnürch, CSO ThioMatrix, was honored with the Science Award of Tyrol 2023
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