Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery
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 Pharmac...
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Dove Medical Press
2020
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oai:doaj.org-article:69dfd2438870475c869b255ac145b72c2021-12-02T11:06:48ZResponse Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery1178-2013https://doaj.org/article/69dfd2438870475c869b255ac145b72c2020-10-01T00:00:00Zhttps://www.dovepress.com/response-surface-methodology-for-statistical-optimization-of-chitosana-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Maryam 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 mhghahremani@tums.ac.irPurpose: 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 nanoparticlesZohri MAkbari Javar HGazori TKhoshayand MRAghaee-Bakhtiari SHGhahremani MHDove Medical Pressarticlealginatebox-behnken design (bbd)chitosanresponse surface methodology (rsm)recombinant human bone morphogenetic protein-2 (rhbmp-2)chitosan/alginate nanoparticlesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 8345-8356 (2020) |
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DOAJ |
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alginate box-behnken design (bbd) chitosan response surface methodology (rsm) recombinant human bone morphogenetic protein-2 (rhbmp-2) chitosan/alginate nanoparticles Medicine (General) R5-920 |
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alginate box-behnken design (bbd) chitosan response surface methodology (rsm) recombinant human bone morphogenetic protein-2 (rhbmp-2) chitosan/alginate nanoparticles Medicine (General) R5-920 Zohri M Akbari Javar H Gazori T Khoshayand MR Aghaee-Bakhtiari SH Ghahremani MH Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery |
description |
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 mhghahremani@tums.ac.irPurpose: 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 |
format |
article |
author |
Zohri M Akbari Javar H Gazori T Khoshayand MR Aghaee-Bakhtiari SH Ghahremani MH |
author_facet |
Zohri M Akbari Javar H Gazori T Khoshayand MR Aghaee-Bakhtiari SH Ghahremani MH |
author_sort |
Zohri M |
title |
Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery |
title_short |
Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery |
title_full |
Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery |
title_fullStr |
Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery |
title_full_unstemmed |
Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery |
title_sort |
response surface methodology for statistical optimization of chitosan/alginate nanoparticles as a vehicle for recombinant human bone morphogenetic protein-2 delivery |
publisher |
Dove Medical Press |
publishDate |
2020 |
url |
https://doaj.org/article/69dfd2438870475c869b255ac145b72c |
work_keys_str_mv |
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