Nanostructured lipid carriers decorated with polyphosphate coated linear and loop cell-penetrating peptides.

Autor: Saleh A; Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82 6020, Innsbruck, Austria; Department of Pharmacy, Universitas Mandala Waluya, A.H.Nasution, Kendari 93231, Southeast Sulawesi, Indonesia., Stengel D; Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82 6020, Innsbruck, Austria., Truszkowska M; Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82 6020, Innsbruck, Austria., Blanco Massani M; Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82 6020, Innsbruck, Austria., Kali G; Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82 6020, Innsbruck, Austria., Bernkop-Schnürch A; 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.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Dec 25; Vol. 667 (Pt A), pp. 124844. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.ijpharm.2024.124844
Abstrakt: Aim: This study aimed to evaluate the cellular uptake of nanostructured lipid carriers (NLCs) decorated with polyphosphate coated linear and loop cell-penetrating peptides (CPPs).
Methods: Linear-CPPs and loop-CPPs were synthesized via ring-opening polymerization and anchored on the surface NLCs, followed by coating with polyphosphate (PP). These nanocarriers (NCs) were characterized in terms of particle size, polydispersity index (PDI), and zeta potential. Cell viability and hemolysis, as well as enzyme-induced charge conversion via phosphate cleavage by free and membrane-bound intestinal alkaline phosphatase (IAP) were investigated. Cellular uptake studies by Caco-2 and HEK cells were quantitatively analyzed by flow cytometry and visualized by confocal microscopy.
Results: A shift in charge from positive to negative was obtained for both linear- and loop-CPPs-NLCs by coating with PP. PP-linear-CPPs-NLCs and PP-loop-CPPs-NLCs exhibited a particle size < 270 nm and a PDI of approximately 0.3. They had a minor effect on cell viability and caused in a concentration of 0.1 % (m/v) around 10 % hemolysis within 24 h. IAP triggered the cleavage and release of monophosphate from the surface of NLCs causing charge conversion from -22.2 mV to + 5.3 mV (Δ27.5 mV) for PP-linear-CPPs-NLCs and from -19.2 mV to + 11.9 mV (Δ31.1 mV) for PP-loop-CPPs-NLCs. Inhibition of alkaline phosphatase activity on Caco-2 and HEK cells confirmed the involvement of this enzyme in charge conversion. PP-linear-CPPs-NLCs showed on Caco-2 cells a higher uptake than PP-loop-CPPs-NLCs, whereas on HEK cells uptake of both types of NLCs was on the same level. The results of cellular uptake were confirmed visually by confocal microscopy.
Conclusion: CPPs-NLCs coated with polyphosphate are a promising approach to overcome the polycationic dilemma and to enhance cellular uptake.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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