ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury

Monireh Azizi; Farhid Farahmandghavi; Mohammad Taghi Joghataei; Mojgan Zandi; Mohammad Imani; Mehrdad Bakhtiari; Hamid Omidian

doi:10.1016/j.ijpharm.2020.119037

ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury

Monireh Azizi
, Farhid Farahmandghavi
, Mohammad Taghi Joghataei
, Mojgan Zandi
, Mohammad Imani
, Mehrdad Bakhtiari
, Hamid Omidian

Research output: Contribution to journal › Article › peer-review

Abstract

Spinal Cord Injury (SCI) is one of the leading causes of physical disability. In this study, spherical PLGA nanoparticles (NPs) containing ChABC enzyme were manufactured and fully characterized for SCI therapy. The NPs were used in the rat’s contused spinal cord to assess the functional improvement and scar digestion. Twenty-three adult male Wistar rats (275 ± 25 g) were assigned into four groups of control, sham, blank-treated particle, and ChABC-treated particle. Throughout the survey, the BBB scores were obtained for all the groups. Finally, the injured sections of animals were dissected, and histological studies were conducted using Luxol fast blue and Bielschowsky. The biocompatibility and non-toxicity effects of the NPs on olfactory ensheathing cells (OECs) were confirmed by the MTT test. The flow-cytometry revealed the purity of cultured OECs with p75+/GFAP+ at around 87.9 ± 2.4%. Animals in the control and the blank-treated groups exhibited significantly lower BBB scores compared with the ChABC-treated particle group. Histological results confirmed the induced contusion models in the injured site. Myelin was observed in the treated groups, especially when the ChABC-loaded nanoparticles were utilized. The immunohistochemistry results indicated the scar glial degradation in animals treated by the ChABC-loaded particles. According to this study, the loaded particles can potentially serve as a suitable candidate for spinal cord repair, functional recovery and axonal regeneration.

Original language	English
Article number	119037
Pages (from-to)	119037
Journal	International journal of pharmaceutics
Volume	577
DOIs	https://doi.org/10.1016/j.ijpharm.2020.119037
State	Published - Mar 15 2020

Bibliographical note

Funding

Current research was granted by Iran National Science Foundation (INSF, Grant No. 89003650) and Cellular-Molecular Research Center of Iran University of Medical Sciences (No. MT458). The authors would like to express their gratitude to Iran Polymer and Petrochemical Institute and Anatomy Department of Iran University of Medical Sciences for their technical support. We would especially like to thank Dr M. Motavalian and Mrs M. Khosravi for providing freeze-drying facilities and performing SEM and point analysis.

ASJC Scopus Subject Areas

Pharmaceutical Science

Keywords

Chondroitinase ABC
OECs
PLGA nanoparticle
Protein delivery
Spinal cord injury
Chondroitin ABC Lyase/chemistry
Olfactory Mucosa/pathology
Spinal Cord Injuries/drug therapy
Cells, Cultured
Locomotion/drug effects
Rats
Cicatrix/drug therapy
Male
Nerve Regeneration/drug effects
Recovery of Function/drug effects
Animals
Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
Nanoparticles/chemistry
Materials Testing/methods

Disciplines

Pharmacy and Pharmaceutical Sciences

Access to Document

10.1016/j.ijpharm.2020.119037

Cite this

Azizi, M., Farahmandghavi, F., Joghataei, M. T., Zandi, M., Imani, M., Bakhtiari, M., & Omidian, H. (2020). ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury. International journal of pharmaceutics, 577, 119037. Article 119037. https://doi.org/10.1016/j.ijpharm.2020.119037

ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury. / Azizi, Monireh; Farahmandghavi, Farhid; Joghataei, Mohammad Taghi et al.
In: International journal of pharmaceutics, Vol. 577, 119037, 15.03.2020, p. 119037.

Research output: Contribution to journal › Article › peer-review

Azizi, M, Farahmandghavi, F, Joghataei, MT, Zandi, M, Imani, M, Bakhtiari, M & Omidian, H 2020, 'ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury', International journal of pharmaceutics, vol. 577, 119037, pp. 119037. https://doi.org/10.1016/j.ijpharm.2020.119037

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abstract = "Spinal Cord Injury (SCI) is one of the leading causes of physical disability. In this study, spherical PLGA nanoparticles (NPs) containing ChABC enzyme were manufactured and fully characterized for SCI therapy. The NPs were used in the rat{\textquoteright}s contused spinal cord to assess the functional improvement and scar digestion. Twenty-three adult male Wistar rats (275 ± 25 g) were assigned into four groups of control, sham, blank-treated particle, and ChABC-treated particle. Throughout the survey, the BBB scores were obtained for all the groups. Finally, the injured sections of animals were dissected, and histological studies were conducted using Luxol fast blue and Bielschowsky. The biocompatibility and non-toxicity effects of the NPs on olfactory ensheathing cells (OECs) were confirmed by the MTT test. The flow-cytometry revealed the purity of cultured OECs with p75+/GFAP+ at around 87.9 ± 2.4\%. Animals in the control and the blank-treated groups exhibited significantly lower BBB scores compared with the ChABC-treated particle group. Histological results confirmed the induced contusion models in the injured site. Myelin was observed in the treated groups, especially when the ChABC-loaded nanoparticles were utilized. The immunohistochemistry results indicated the scar glial degradation in animals treated by the ChABC-loaded particles. According to this study, the loaded particles can potentially serve as a suitable candidate for spinal cord repair, functional recovery and axonal regeneration.",

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AU - Azizi, Monireh

AU - Farahmandghavi, Farhid

AU - Joghataei, Mohammad Taghi

AU - Zandi, Mojgan

AU - Imani, Mohammad

AU - Bakhtiari, Mehrdad

AU - Omidian, Hamid

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N2 - Spinal Cord Injury (SCI) is one of the leading causes of physical disability. In this study, spherical PLGA nanoparticles (NPs) containing ChABC enzyme were manufactured and fully characterized for SCI therapy. The NPs were used in the rat’s contused spinal cord to assess the functional improvement and scar digestion. Twenty-three adult male Wistar rats (275 ± 25 g) were assigned into four groups of control, sham, blank-treated particle, and ChABC-treated particle. Throughout the survey, the BBB scores were obtained for all the groups. Finally, the injured sections of animals were dissected, and histological studies were conducted using Luxol fast blue and Bielschowsky. The biocompatibility and non-toxicity effects of the NPs on olfactory ensheathing cells (OECs) were confirmed by the MTT test. The flow-cytometry revealed the purity of cultured OECs with p75+/GFAP+ at around 87.9 ± 2.4%. Animals in the control and the blank-treated groups exhibited significantly lower BBB scores compared with the ChABC-treated particle group. Histological results confirmed the induced contusion models in the injured site. Myelin was observed in the treated groups, especially when the ChABC-loaded nanoparticles were utilized. The immunohistochemistry results indicated the scar glial degradation in animals treated by the ChABC-loaded particles. According to this study, the loaded particles can potentially serve as a suitable candidate for spinal cord repair, functional recovery and axonal regeneration.

AB - Spinal Cord Injury (SCI) is one of the leading causes of physical disability. In this study, spherical PLGA nanoparticles (NPs) containing ChABC enzyme were manufactured and fully characterized for SCI therapy. The NPs were used in the rat’s contused spinal cord to assess the functional improvement and scar digestion. Twenty-three adult male Wistar rats (275 ± 25 g) were assigned into four groups of control, sham, blank-treated particle, and ChABC-treated particle. Throughout the survey, the BBB scores were obtained for all the groups. Finally, the injured sections of animals were dissected, and histological studies were conducted using Luxol fast blue and Bielschowsky. The biocompatibility and non-toxicity effects of the NPs on olfactory ensheathing cells (OECs) were confirmed by the MTT test. The flow-cytometry revealed the purity of cultured OECs with p75+/GFAP+ at around 87.9 ± 2.4%. Animals in the control and the blank-treated groups exhibited significantly lower BBB scores compared with the ChABC-treated particle group. Histological results confirmed the induced contusion models in the injured site. Myelin was observed in the treated groups, especially when the ChABC-loaded nanoparticles were utilized. The immunohistochemistry results indicated the scar glial degradation in animals treated by the ChABC-loaded particles. According to this study, the loaded particles can potentially serve as a suitable candidate for spinal cord repair, functional recovery and axonal regeneration.

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KW - Recovery of Function/drug effects

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KW - Polylactic Acid-Polyglycolic Acid Copolymer/chemistry

KW - Nanoparticles/chemistry

KW - Materials Testing/methods

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JO - International journal of pharmaceutics

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ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

Keywords

Disciplines

Access to Document

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