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


Erzengin S., Guler E., Eser E., Polat E. B., Gunduz O., Cam M. E.

International Journal of Biological Macromolecules, cilt.204, ss.429-440, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 204
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.ijbiomac.2022.02.030
  • Dergi Adı: International Journal of Biological Macromolecules
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, INSPEC, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.429-440
  • Anahtar Kelimeler: Diabetes mellitus, Insulin delivery, Transmucosal delivery, 3D printing, Pharmacokinetic, Composite scaffold, BUCCAL DELIVERY, DRUG-DELIVERY, NANOPARTICLES, ALGINATE, RELEASE, POLYMER, COMPLEX
  • Marmara Üniversitesi Adresli: Evet

Özet

© 2022 Elsevier B.V.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.