Artikel
IGF-1 Nanoparticles to Ameliorate Effects of Chronic Denervation Following Peripheral Nerve Injury
Meeting Abstract
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Autoren
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Philip Hanwright
- Johns Hopkins University School of Medicine, Baltimore, United States
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Chenhu Qiu
- Johns Hopkins Whiting School of Engineering, Baltimore, United States
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Jennifer Rath
- Johns Hopkins University School of Medicine, Baltimore, United States
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Nicholas Von Guionneau
- Johns Hopkins University School of Medicine, Baltimore, United States
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Karim Sarhane
- Johns Hopkins University School of Medicine, Baltimore, United States
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Thomas Harris
- Johns Hopkins University School of Medicine, Baltimore, United States
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Harsha Malapati
- Johns Hopkins University School of Medicine, Baltimore, United States
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Ahmet Hoke
- Johns Hopkins University School of Medicine, Baltimore, United States
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Hai-Quan Mao
- Johns Hopkins Whiting School of Engineering, Baltimore, United States
-
Sami Tuffaha
- Johns Hopkins University School of Medicine, Baltimore, United States
| Veröffentlicht: | 6. Februar 2020 |
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Gliederung
Text
Objectives/Interrogation: Insulin-like growth factor 1 (IGF-1) is a potent mitogen with well-described trophic and anti-apoptotic effects on neurons, myocytes, and Schwann cells (SC). Local delivery of IGF-1 is limited by its short-half life. The aims of this study are to
- 1.
- encapsulate IGF-1 into biodegradable nanoparticles (NP) that stabilize IGF-1 in its bioactive state and enable sustained release at target tissue sites; and
- 2.
- assess the efficacy of locally delivered IGF-1 NPs in augmenting axonal regeneration while also reducing denervation-induced muscle and SC atrophy to thereby improve functional recovery following nerve injury.
Methods:
- 1.
- NP Fabrication: IGF-1 was first complexed with dextran sulfate to create hydrophobic ionic paired (HIP) complexes, which were then encapsulated in biodegradable PGLA NPs. Varying ratios of HIP:polymer were evaluated to maximize loading efficiency and release kinetics. In vitro NP release kinetics were evaluated and mitogenic activity of released IGF-1 was compared to native IGF-1.
- 2.
- The effects of locally-delivered IGF-1 NPs on denervated muscle and Schwann cells were assessed in a rat median nerve transection-without-repair model. The effects of IGF-1 NPs on axonal regeneration, muscle atrophy and reinnervation, and recovery of forepaw function were assessed in a model in which chronic denervation is induced prior to nerve repair; functional recovery was assessed weekly with stimulated grip strength testing prior to sacrifice at 15 weeks.
Results and Conclusions:
- 1.
- Fabrication of uniform NPs with an encapsulation efficiency of 83.2% was achieved. 1:5 PEG5k-PCL40k formulation yielded optimal release of IGF-1. Near-zero-order release of IGF-1 can be achieved for at least 70 days, and released IGF-1 exhibits comparable bioactivity to native IGF-1.
- 2.
- IGF-1 treated animals recovered significantly more forceful grip strength compared to negative controls (Figure 1 [Fig. 1]). IGF-1 NP treatment limits muscle atrophy during periods of denervation compared to negative controls (620 vs. 340um2; p <0.05) and enhances neuromuscular junction reinnervation (41 vs. 27%, p <0.05) (Figure 1 [Fig. 1]).
