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Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform

  • Limited drug loading capacity (LC), mostly below 5% w/w, is a significant drawback of nanoparticulate drug delivery systems (DDS). Squalenoylation technology, which employs bioconjugation of squalenyl moiety and drug, allows self-assemble of nanoparticles (NPs) in aqueous media with significantly high LC (>30% w/w). The synthesis and particle preparation of squalenoylated prodrugs are, however, not facile for molecules with multiple reactive groups. Taking a different approach, we describe the synthesis of amphiphilic squalenyl derivatives (SqDs) as well as the physicochemical and biopharmaceutical characterizations of their self-assembled NPs as DDSs. The SqDs included in this study are (i) cationic squalenyl diethanolamine (ii) PEGylated SqD (PEG 750 Da), (iii) PEGylated SqD (PEG 3,000 Da), and (iv) anionic squalenyl hydrogen sulfate. All four SqDs self-assemble into NPs in a size range from 100 to 200 nm in an aqueous solution. Furthermore, all NP derivatives demonstrate appropriate biocompatibility and adequate colloidal stability in physiological relevant pH environments. The mucoprotein binding of PEGylated NPs is reduced compared to the charged NPs. Most importantly, this technology allows excellent LC (at maximum of 45% w/w) of a wide range of multifunctional compounds, varying in physicochemical properties and molecular weight. Interestingly, the drug release profile can be tuned by different loading methods. In summary, the SqD-based NPs appear as versatile drug delivery platforms.

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Document Type:Article
Author:Duy-Khiet HoORCiD, Rebekka ChristmannORCiD, Xabier MurgiaORCiD, Chiara De Rossi, Sarah Frisch, Marcus Koch, Ulrich F. Schaefer, Brigitta LoretzORCiD, Didier Desmaele, Patrick Couvreur, Claus-Michael LehrORCiD
Parent Title (English):Frontiers in Chemistry
Year of first Publication:2020
Release Date:2022/11/18
Tag:drug delivery; nanoparticles; pegylated; protein-interaction; self-assemble; squalene; squalenyl derivatives
Impact:05.221 (2020)
Funding Information:European Union's Framework Programme for Research and Innovation Horizon 2020 (2014–2020) under the Marie Sklodowska-Curie Grant Agreement No. 642028; Deutsche Forschungsgemeinschaft (DFG; German Research Foundation)
Research Departments:Physikalische Analytik
Open Access:Open Access
Signature:INM 2020/116
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International