Charge changing phosphorylated polymers: Proof of in situ mucoadhesive properties.
The objective of this study was to design a novel polyethylene glycol (PEG) derivative exhibiting mucus permeating and mucoadhesive properties. Therefore, the enzymatically degradable phosphate ester, phosphotyrosine (Ptyr) was covalently attached to PEG-diamine. The synthesized PEG-Ptyr was studied in terms of enzymatic degradability on Caco 2 cells and by isolated intestinal alkaline phosphatase (IAP). Furthermore, the influence of enzymatic degradation on charge distribution of the polymer as well as on mucus diffusion and mucoadhesion was investigated. Within this study, the phosphate ester in PEG-Ptyr could be cleaved on the cell monolayer and by the isolated IAP, whereby the degradation rate was 10-fold higher utilizing the isolated enzyme. Implementation of negative charges on PEG due to modification with Ptyr led to an increased electrophoretic mobility, which was reduced after enzymatic degradation of the phosphate ester, most likely due to the alterations in charge distribution on the polymeric backbone. Interactions with mucus components were determined within mucus diffusion studies and rheological investigations. Herein, PEG-Ptyr showed a 3-fold lower mucus diffusion, after incubation with IAP. Within rheological investigations, dynamic viscosities increased by the factor of 3, after the phosphate ester in PEG-Ptyr was degraded by IAP. Results obtained within these experiments provided evidence for the in situ mucoadhesive properties of charge changing phosphorylated polymers. The combination of mucus permeating and mucoadhesive features of phosphorylated PEGs could be a highly interesting tool for future applications, such as for coating nanoparticles.
Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Sonja
S
Bonengel
Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Max
M
Jelkmann
Sagetis Biotech, SL, Via Augusta 394, 08017 Barcelona, Spain.
Sejin
S
Oh
Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Arshad
A
Mahmood
Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Muhammad
M
Ijaz
Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
Andreas
A
Bernkop-Schnürch
D009093:Mucus / Q000737:chemistry*; D010766:Phosphorylation; D011108:Polymers / Q000737:chemistry*; D014014:Tissue Adhesives / Q000737:chemistry*
D011108:Polymers; D014014:Tissue Adhesives
Charge changing polymers; In situ mucoadhesion; Intestinal alkaline phosphatase; Phosphotyrosine; Polyethylene glycol