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Preparation, Characterization and in Vivo Evaluation of a Combination Delivery System Based on Hyaluronic Acid/Jeffamine Hydrogel Loaded With Phbv/Plga Blend Nanoparticles for Prolonged Delivery of Teriparatide Publisher Pubmed



Bahari Javan N1 ; Montazeri H2 ; Rezaie Shirmard L3 ; Jafary Omid N1 ; Barbari GR1 ; Amini M4, 5 ; Ghahremani MH6 ; Rafieetehrani M1 ; Abedin Dorkoosh F1, 7
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
  4. 4. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran

Source: European Journal of Pharmaceutical Sciences Published:2017


Abstract

In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50 days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD50 of Teriparatide loaded CDS was 131.8 mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins. © 2017 Elsevier B.V.
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