AAPS PharmSciTech

, Volume 13, Issue 2, pp 590–600 | Cite as

Preparation and Investigation of Sustained Drug Delivery Systems Using an Injectable, Thermosensitive, In Situ Forming Hydrogel Composed of PLGA–PEG–PLGA

  • Elham Khodaverdi
  • Farnaz Sadat Mirzazadeh Tekie
  • Seyed Ahmad Mohajeri
  • Fariba Ganji
  • Gholamhossein Zohuri
  • Farzin Hadizadeh
Research Article


In situ gelling systems are very attractive for pharmaceutical applications due to their biodegradability and simple manufacturing processes. The synthesis and characterization of thermosensitive poly(d,l-lactic-co-glycolic acid) (PLGA)–polyethylene glycol (PEG)–PLGA triblock copolymers as in situ gelling matrices were investigated in this study as a drug delivery system. Ring-opening polymerization using microwave irradiation was utilized as a novel technique, and the results were compared with those using a conventional method of polymerization. The phase transition temperature and the critical micelle concentration (CMC) of the copolymer solutions were determined by differential scanning calorimetry and spectrophotometry, respectively. The size of the micelles was determined with a light scattering method. In vitro drug release studies were carried out using naltrexone hydrochloride and vitamin B12 as model drugs. The rate and yield of the copolymerization process via microwave irradiation were higher than those of the conventional method. The copolymer structure and concentration played critical roles in controlling the sol–gel transition temperature, the CMC, and the size of the nanomicelles in the copolymer solutions. The rate of drug release could be modulated by the molecular weight of the drugs, the concentration of the copolymers, and their structures in the formulations. The amount of release versus time followed zero-order release kinetics for vitamin B12 over 25 days, in contrast to the Higuchi modeling for naltrexone hydrochloride over a period of 17 days. In conclusion, PLGA–PEG1500–PLGA with a lactide-to-glycolide ratio of 5:1 is an ideal system for the long-acting, controlled release of naltrexone hydrochloride and vitamin B12.


hydrogel naltrexone PLGA–PEG–PLGA thermosensitive triblock copolymer vitamin B12 



The authors are grateful for the financial support provided by Mashhad University of Medical Sciences for this study. The results described in this paper were part of a Pharm D student’s thesis proposal.


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Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Elham Khodaverdi
    • 1
    • 6
  • Farnaz Sadat Mirzazadeh Tekie
    • 2
  • Seyed Ahmad Mohajeri
    • 3
  • Fariba Ganji
    • 4
  • Gholamhossein Zohuri
    • 5
  • Farzin Hadizadeh
    • 2
  1. 1.Department of Pharmaceutics, School of PharmacyMashhad University of Medical SciencesMashhadIran
  2. 2.Biotechnology Research Center, School of PharmacyMashhad University of Medical SciencesMashhadIran
  3. 3.Pharmaceutical Research Center, School of PharmacyMashhad University of Medical SciencesMashhadIran
  4. 4.Biotechnology Group, Faculty of Chemical EngineeringTarbiat Modares UniversityTehranIran
  5. 5.Department of Chemistry, Faculty of ScienceFerdowsi UniversityMashhadIran
  6. 6.Drug Delivery Research Center, School of PharmacyMashhad University of Medical SciencesMashhadIran

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