Journal of the Iranian Chemical Society

, Volume 14, Issue 12, pp 2637–2648 | Cite as

Micelles of polylactide–poly(ethylene glycol)–polylactide (LA n –EG m –LA n ) triblock copolymers as insulin delivery system: spectroscopic studies

  • Pouneh Sadat PourhosseiniEmail author
  • Reza Amani
  • Ali Akbar Saboury
  • Farhood Najafi
  • Mohammad Imani
Original Paper


A series of triblock copolymers are synthesized by the ring-opening polymerization of l-lactide in the presence of PEG of various molecular weights. Firstly, the (lactic acid) n –(ethylene glycol) m –(lactic acid) n (LA n –EG m –LA n ) copolymers are characterized by 1H NMR and GPC studies. Micelles, prepared in aqueous media by the direct dissolution method, are characterized by TEM and DLS. In vitro release behavior of bovine insulin from LA37–EG136–LA37 micelles is evaluated at 37 °C. According to results, nearly 90 wt% of insulin is released over 6 days by diffusion in a biphasic pattern. Secondly, a comparative study of the interactions occurring between insulin (both bovine and human) and the LA37–EG136–LA37 triblock copolymer is carried out using different spectroscopic techniques. UV–visible spectroscopy shows that the copolymer binds spontaneously to both proteins with a similar stoichiometry. However, a higher affinity was observed for bovine insulin. Far-UV CD spectroscopy reveals that the secondary structure of both proteins changes in the presence of the copolymer, although the extent of changes in bovine insulin is larger. Acrylamide quenching experiments display reduced accessibility of tyrosines at high copolymer concentrations. In these conditions, the major decrease in the α-helical content of the proteins causes tyrosines to be exposed to the nonpolar environment of the micelles and thus shielded from the aqueous solvent. Results demonstrate that upon interaction with the copolymer, the microenvironment around tyrosines is rearranged, the extent of which depends on the copolymer concentration. Altogether, drug–copolymer interactions need to be considered when attempting to use polymeric formulations as delivery carriers of peptide drugs.


Insulin Circular dichroism (CD) Fluorescence spectroscopy Polylactide (PLA) Triblock copolymer 



Circular dichroism




Hepatitis B surface antigen


Hydrophilic–lipophilic balance


(Lactic acid) n –(ethylene glycol) m –(lactic acid) n


Poly(ethylene glycol)


Poly(ethylene oxide)


Poly(lactic acid)


Gel permeation chromatography



The authors thank the Iran National Science Foundation (INSF) and Research Council of University of Tehran for their financial support.

Supplementary material

13738_2017_1198_MOESM1_ESM.docx (112 kb)
Supplementary material 1 (DOCX 112 kb)


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Copyright information

© Iranian Chemical Society 2017

Authors and Affiliations

  • Pouneh Sadat Pourhosseini
    • 1
    Email author
  • Reza Amani
    • 2
  • Ali Akbar Saboury
    • 2
  • Farhood Najafi
    • 3
  • Mohammad Imani
    • 4
  1. 1.Faculty of Biological SciencesAlzahra UniversityTehranIran
  2. 2.Institute of Biochemistry and BiophysicsUniversity of TehranTehranIran
  3. 3.Department of Resin and AdditivesInstitute for Color Science and TechnologyTehranIran
  4. 4.Iran Polymer and Petrochemical InstituteTehranIran

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