Stimuli-responsive polypeptide nanogels loaded with α1-antitrypsin for inhibition of inflammatory mediator trypsin

  1. Petr ŠálekORCID Logo,
  2. Jana Dvořáková,
  3. Sviatoslav Hladysh,
  4. Diana Oleshchuk,
  5. Ewa PavlovaORCID Logo,
  6. Jan KučkaORCID Logo and
  7. Vladimír ProksORCID Logo

Submitting author affiliation: Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague 6, Czech Republic

Beilstein Arch. 2021, 202191. https://doi.org/10.3762/bxiv.2021.91.v1

Published 23 Dec 2021

  • Preprint

Abstract

A new type of hydrophilic, biocompatible, and biodegradable polypeptide nanogel depots loaded with natural serine protease inhibitor α1-antitrypsin (AAT) was applied for inhibition of inflammatory mediator trypsin. Further, poly[N5-(2-hydroxyethyl)-L-glutamine-ran-N5-propargyl-L-glutamine-ran-N5-(6-aminohexyl)-L-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-L-glutamine] (PHEG-Tyr) and Nα-L-Lysine-grafted α,β-poly[(2-propyne)-D,L-aspartamide-ran-(2-hydroxyethyl)-DL-aspartamide-ran-(2-(4-hydroxyphenyl)ethyl)-DL-aspartamide] (Nα-Lys-NG) nanogels were prepared by HRP/H2O2-mediated crosslinking in inverse miniemulsions with pH and temperature-stimuli responsive behavior confirmed by dynamic light scattering and zeta potential measurements. The loading capacity of PHEG-Tyr and Nα-Lys-NG nanogels and their release profiles were firstly optimized with bovine serum albumin (BSA) and then used for loading and release of AAT. PHEG-Tyr and Nα-Lys-NG nanogels showed different loading capacities for AAT with the maximum (20 %) achieved with Nα-Lys-NG nanogel. In both cases, the nanogels depots demonstrated a burst release of AAT during 6 h, which could be favorable for quick inhibition of trypsin. A consequent pilot in vitro inhibition study revealed that both PHEG-Tyr and Nα-Lys-NG nanogels loaded with AAT successfully inhibited the enzymatic activity of trypsin. Furthermore, the inhibitory efficiency of the AAT-loaded nanogels was higher than that of AAT itself, indicating that the negatively charged polypeptide nanogels enhance the inhibitory function of AAT loaded in the nanogel depots.

Keywords: α1-antitrypsin, inflammatory mediator, nanogel, polypeptide, trypsin

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When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:

Šálek, P.; Dvořáková, J.; Hladysh, S.; Oleshchuk, D.; Pavlova, E.; Kučka, J.; Proks, V. Beilstein Arch. 2021, 202191. doi:10.3762/bxiv.2021.91.v1

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© 2021 Šálek et al.; licensee Beilstein-Institut.
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