In vitro and in vivo evaluation of 3D printed sodium alginate/polyethylene glycol scaffolds for sublingual delivery of insulin: Preparation, characterization, and pharmacokinetics

Int J Biol Macromol. 2022 Apr 15:204:429-440. doi: 10.1016/j.ijbiomac.2022.02.030. Epub 2022 Feb 10.

Abstract

Delivery of therapeutic peptides via sublingual administration is extremely desired and 3D printed scaffolds are potential candidates as carriers to enhance insulin delivery. 3D printed sublingual sodium alginate (SA)/polyethylene glycol (PEG) composite scaffolds were produced for enhancing insulin delivery by examining the chemical, morphological, mechanical, thermal, cytotoxic, and pharmacokinetic features. The tensile strength and flexibility of scaffolds increased after loading insulin due to the crystalline structure of insulin. Furthermore, insulin-loaded 9SA/3PEG scaffolds showed ultrafast wetting (<1 s), disintegration (<6 s), and also dissolution (<30 s) according to Hixson-Crowell kinetic model. The cell viability of L929 cells on 3D printed scaffolds was examined and these scaffolds could be safely applied on animals. Pharmacokinetic parameters and blood glucose level were evaluated following sublingual administration of scaffolds to type-1 diabetic rats. A single dose of scaffold presented a longer hypoglycemic effect, reducing ~60% of glycemia after 30 min and it lasted for 12 h by increasing the bioavailability of insulin. Scaffolds indicated a sustained profile for serum insulin levels, which continued to increase slightly after 3 h during the study. The polymeric scaffold with a high safety and efficacy holds a new promising delivery strategy for administering injectable insulin through the sublingual route.

Keywords: 3D printing; Composite scaffold; Diabetes mellitus; Insulin delivery; Pharmacokinetic; Transmucosal delivery.

MeSH terms

  • Administration, Sublingual
  • Alginates* / chemistry
  • Animals
  • Diabetes Mellitus, Experimental* / drug therapy
  • Insulin
  • Polyethylene Glycols / chemistry
  • Printing, Three-Dimensional
  • Rats
  • Tissue Engineering
  • Tissue Scaffolds

Substances

  • Alginates
  • Insulin
  • Polyethylene Glycols