Biocompatibility of insulin-PLA stereocomplex

Tovi Shapira-Furman, Abraham Nyska, Abraham J. Domb

Research output: Contribution to journalArticlepeer-review

Abstract

Biocompatibility is essential for drug delivery systems to ensure safety. Poly(lactic acid) (PLA) and its copolymers with glycolic acid and caprolactone, are known as safe biodegradable implants and carriers of drugs in clinical use. These polymers have been clinically used for the delivery of peptides, such as: LHRH, somatostatin and growth hormone. While the safety of PLA has been confirmed, the biocompatibility of PLA- based stereocomplexes with peptides has not been investigated. Stereocomplex is a complex formed by two molecules with opposite enantiomeric configuration. D-PLA consists of a chiral monomer thus can adopts a three dimensional structure which is a mirror image of a helix structure, therefore, complexes with insulin into a stereocomplex. In previous reports we demonstrated the formation of such stereocomplex. This study presents the safety evolution of a stereocomplex composed of the water soluble diblock copolymer of D-polylactic acid-co-polyetheylene glycol (DPLA-PEG) and Insulin, following subcutaneous administration of 17 mg sterecomoplex/mouse to Akita−/+ins2 mice. The mice were monitored for blood glucose levels and weight along the experiment, while growth necropsy and histopathology examination were done post sacrificing. Results demonstrated normal body weight gain with no pathological finding of an internal organ and no inflammatory signs at the injection site except of minimal macrophages, after 16 weeks following polymer administration. Hence, Stereocomplex of D-PLA-PEG/insulin is considered biocompatible with no adversity.

Original languageEnglish
JournalJournal of Bioactive and Compatible Polymers
DOIs
StateAccepted/In press - 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • PLA
  • biocompatibility
  • insulin
  • stereocomplex
  • sustained delivery

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