Amphiphilic star polypept(o)ides as nanomeric vectors in mucosal drug delivery.
journal contributionposted on 28.04.2021, 00:33 by Dimitrios Skoulas, Vivien Stuttgen, Rachel GaulRachel Gaul, Sally-Ann CryanSally-Ann Cryan, David J. Brayden, Andreas HeiseAndreas Heise
Mucosal delivery across the gastrointestinal (GI) tract, airways, and buccal epithelia is an attractive mode of therapeutic administration, but the challenge is to overcome the mucus and epithelial barriers. Here, we present degradable star polypept(o)ides capable of permeating both barriers as a promising biomaterial platform for mucosal delivery. Star polypept(o)ides were obtained by the initiation of benzyl-l-glutamate N-carboxyanhydride (NCA) from an 8-arm poly(propyleneimine) (PPI) dendrimer, with subsequent chain extension with sarcosine NCA. The hydrophobic poly(benzyl-l-glutamate) (PBLG) block length was maintained at 20 monomers, while the length of the hydrophilic poly(sarcosine) (PSar) block ranged from 20-640 monomers to produce star polypept(o)ides with increasing hydrophilic: hydrophobic ratios. Transmission electron microscopy (TEM) images revealed elongated particles of ∼120 nm length, while dynamic light scattering (DLS) provided evidence of a decrease in the size of polymer aggregates in water with increasing poly(sarcosine) block length, with the smallest size obtained for the star PBLG20-b-PSar640. Fluorescein isothiocyanate (FITC)-conjugated PBLG20-b-PSar640 permeated artificial mucus and isolated rat mucus, as well as rat intestinal jejunal tissue mounted in Franz diffusion chambers. An apparent permeability coefficient (Papp) of 15.4 ± 3.1 ×10-6 cm/s for FITC-PBLG20-b-PSar640 was calculated from the transepithelial flux obtained with the apical-side addition of 7.5 mg polypept(o)ide to jejunal tissue over 2 h. This Papp could not be accounted for by flux of unconjugated FITC. Resistance to trypsin demonstrated the stability of FITC-labeled polypept(o)ide over 2 h, but enzymatic degradation at the mucus-epithelial interface or during flux could not be ruled out as contributing to the Papp. The absence of any histological damage to the jejunal tissue during the 2 h exposure suggests that the flux was not associated with overt toxicity.
CÚRAM - Centre for Research in Medical Devices
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Science Foundation Ireland (SFI)
European Regional Development Fund (ERDF) under grant number 13/RC/2073.
CommentsThis document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Biomacromolecules, copyright © American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/acs.biomac.0c00381
Published CitationSkoulas D, Stuettgen V, Gaul R, Cryan SA, Brayden DJ, Heise A. Amphiphilic star polypept(o)ides as nanomeric vectors in mucosal drug delivery. Biomacromolecules. 2020;21(6):2455-2462.
Publication Date28 April 2020
- Amber (Advanced Material & Bioengineering Research) Centre
- RCSI Tissue Engineering Group (TERG)
- School of Pharmacy and Biomolecular Sciences
- Cu00daRAM Centre for Research in Medical Devices
- Biomaterials and Regenerative Medicine
- Accepted Version (Postprint)