Nanosponges as protein delivery systems: Insulin, a case study

Silvia Lucia Appleton; Maria Tannous; Monica Argenziano; Elisabetta Muntoni; Arianna Carolina Rosa; Davide Rossi; Fabrizio Caldera; Anna Scomparin; Francesco Trotta; Roberta Cavalli

doi:10.1016/j.ijpharm.2020.119888

Nanosponges as protein delivery systems: Insulin, a case study

Int J Pharm. 2020 Nov 30:590:119888. doi: 10.1016/j.ijpharm.2020.119888. Epub 2020 Sep 18.

Authors

Affiliations

¹ Department of Chemistry, University of Turin, via P. Giuria 7, 10125 Turin, Italy. Electronic address: silvialucia.appleton@unito.it.
² Department of Chemistry, University of Turin, via P. Giuria 7, 10125 Turin, Italy. Electronic address: maria.tannous@unito.it.
³ Department of Drug Science and Technology, University of Turin, via P. Giuria 9, 10125 Turin, Italy. Electronic address: monica.argenziano@unito.it.
⁴ Department of Drug Science and Technology, University of Turin, via P. Giuria 9, 10125 Turin, Italy. Electronic address: elisabetta.muntoni@unito.it.
⁵ Department of Drug Science and Technology, University of Turin, via P. Giuria 9, 10125 Turin, Italy. Electronic address: ariannacarolina.rosa@unito.it.
⁶ Department of Chemistry, University of Turin, via P. Giuria 7, 10125 Turin, Italy. Electronic address: davide.rossi@unito.it.
⁷ Department of Chemistry, University of Turin, via P. Giuria 7, 10125 Turin, Italy. Electronic address: fabrizio.caldera@unito.it.
⁸ Department of Drug Science and Technology, University of Turin, via P. Giuria 9, 10125 Turin, Italy. Electronic address: anna.scomparin@unito.it.
⁹ Department of Chemistry, University of Turin, via P. Giuria 7, 10125 Turin, Italy. Electronic address: francesco.trotta@unito.it.
¹⁰ Department of Drug Science and Technology, University of Turin, via P. Giuria 9, 10125 Turin, Italy. Electronic address: roberta.cavalli@unito.it.

PMID: 32950667
DOI: 10.1016/j.ijpharm.2020.119888

Abstract

Cyclodextrin-based nanosponges have been found to bepromising drug delivery systems. This paper investigates an application that still needs to be studied in depth, that is, the oral delivery of peptides and proteins, choosing insulin as a case study. The nanospongewas synthesized by crosslinkingβ-cyclodextrins withpyromellitic dianhydride, adopting a top-down approach for its subsequent formulation. Aphysicochemical characterization, in-vitro andin-vivo tests were carried out on the formulation developed. It was nanometric (around 250 nm) with high negative zeta potential, mucoadhesion and swelling properties, good loading capability (about 14%) and encapsulation efficiency (above 90%). The in-vitro release of insulin was negligible at a gastric pH (below 2%) while sustained at an intestinal pH, thus showing a pH-sensitive behaviour of the nanosponge. The Caco-2 cell permeability assay proved that the intestinal permeation of insulin was enhanced when loaded inside the nanosponge. The in-vivo studies confirmed the presence of insulin in rat plasma and a marked hypoglycemic effect in diabetic mice after duodenal and oral administrations, respectively. These preliminary results are encouraging with a view to continuing to study this β-cyclodextrin nanosponge technology for the oral administration of insulin and extending this approach to other proteins of pharmaceutical interest.

Keywords: Cyclodextrin; Insulin; Nanosponges; Oral delivery; Proteins; pH-sensitive.

MeSH terms

Administration, Oral
Animals
Caco-2 Cells
Cyclodextrins*
Diabetes Mellitus, Experimental* / drug therapy
Drug Carriers
Drug Delivery Systems
Humans
Insulin
Mice
Rats

Substances

Cyclodextrins
Drug Carriers
Insulin