International Journal of Nanomedicine (Oct 2020)

Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery

  • Zohri M,
  • Akbari Javar H,
  • Gazori T,
  • Khoshayand MR,
  • Aghaee-Bakhtiari SH,
  • Ghahremani MH

Journal volume & issue
Vol. Volume 15
pp. 8345 – 8356

Abstract

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Maryam Zohri,1 Hamid Akbari Javar,2 Taraneh Gazori,3 Mohammad Reza Khoshayand,4 Seyed Hamid Aghaee-Bakhtiari,5,6 Mohammad Hossein Ghahremani1,7 1Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Departments of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 3Research and Development Department, Trita Nano Pharmaceutical Research Center, Tehran, Iran; 4Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 5Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad, Iran; 6Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 7Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranCorrespondence: Mohammad Hossein Ghahremani Tel/Fax +9866959102Email [email protected]: In this study, chitosan/alginate nanoparticles are prospected as a carrier for controlled release of recombinant human bone morphogenetic protein-2 (rhBMP-2).Materials and Methods: The rhBMP-2-loaded chitosan/alginate nanoparticles (Cs/Alg/B NPs) were prepared using the ionic gelation (IG) method. The current research was conducted to optimize the effective factors for entrapping rhBMP-2 in Cs/Alg NPs using response surface methodology (RSM) and the Box–Behnken design (BBD). The variables were the Cs/Alg molecular weight (Mw) ratios (1– 3), pH (4.8– 5.5), stirring rates (900– 1300 rpm) and the responses included size, ζ-potential, polydispersity index (PDI), loading efficacy (LE), cumulative release (CR), and morphological degradation time (MDE). Then, the morphological properties of optimum formulation were studied for post-characterization. In the next step, the MTT assay for the optimized run was done for 24 and 48 hours.Results: The results revealed that the optimum conditions for the mentioned variables were stirring rate=1100 rpm, pH=5.15, and Cs/Alg Mw ratio=1.75 based on numerical optimization. It was shown that the average particle size and loading efficacy at optimum conditions were 253 nm and 67%, respectively. Other responses were as follows: CR=66%, ζ-potential=+35mV, PDI=0.5, and MDT=7 days.Conclusion: The results have suggested that the statistical optimization of rhBMP-2 offers the possibility of preparing Cs/Alg/B NPs with a favorable size, controlled release characteristics, and high loading efficiency. It is expected that the acquired optimum conditions will be useful for efficient rhBMP-2 delivery.Keywords: alginate, Box–Behnken design(BBD), chitosan, response surface methodology (RSM), recombinant human bone morphogenetic protein-2 (rhBMP-2), chitosan/alginate nanoparticles

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