Critical parameters for the controlled synthesis of nanogels suitable for temperature-triggered protein delivery.

Autor: Theune LE; Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany., Charbaji R; Freie Universität Berlin, Institute for Pharmacy (Pharmacology and Toxicology), Königin-Luise-Str. 2+4, 14195 Berlin, Germany., Kar M; Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany., Wedepohl S; Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany., Hedtrich S; Freie Universität Berlin, Institute for Pharmacy (Pharmacology and Toxicology), Königin-Luise-Str. 2+4, 14195 Berlin, Germany; University of British Columbia, Faculty of Pharmaceutical Sciences, 2405 Wesbrook Mall, V6T 1Z3, Vancouver, Canada., Calderón M; Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany. Electronic address: marcelo.calderon@fu-berlin.de.
Jazyk: angličtina
Zdroj: Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2019 Jul; Vol. 100, pp. 141-151. Date of Electronic Publication: 2019 Feb 23.
DOI: 10.1016/j.msec.2019.02.089
Abstrakt: Macromolecular bioactives, like proteins and peptides, emerged as highly efficient therapeutics. The main limitation for their clinical application is their instability and potential immunogenicity. Thus, controlled delivery systems able protect the proteins prior release are highly on demand. In the present study, we developed hydrophilic thermo-responsive nanogels with tunable volume phase transition temperatures (VPTTs) and suitable features for controlled protein delivery by the use of multifunctional, dendritic polyglycerol (dPG) as macromolecular cross-linker and temperature-sensitive polymers poly(N-isopropylacrylamide) (NIPAM) and poly(N-isopropylacrylmethacrylate) as linear counterpart. We comprehensively studied the impact of the initiator, monomers and cross-linker on the nanogel structure during the synthesis. Careful analysis of the polymerization process revealed importance of balanced reactions kinetics to form particles with diameters in the range 100-200 nm and low polydispersity. We can control the cross-linking density of the nanogels mainly by the dPG feed and its degree of acrylation. In addition, our screenings revealed that the hydrophilic character of dPG enables it to stabilize the growing particles during the polymerization and thereby reduces final particle size. Co-polymerization of NIPAM and NIPMAM allows precise tuning of the VPTT of the nanogels in the desired range of 34-47 °C. Our nanogels showed outstanding high protein encapsulation efficiency and triggered cargo release upon a temperature change. The delivery efficiency of these nanogels was investigated on excised human skin demonstrating efficient dermal penetration of encapsulated proteins dependent on a temperature triggered release mechanism.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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