Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats.

Zhang CX, Cheng Y, Liu DZ, Liu M, Cui H, Zhang BL, Mei QB, Zhou SY

Journal of nanobiotechnology25 Jan 2019Cited by 191 (Europe PMC)

PMID30683110PMCIDPMC6346555DOI10.1186/s12951-019-0451-9PepBankPUB-30683110

Summary

BackgroundCyclosporin A (CsA) is a promising therapeutic drug for myocardial ischemia reperfusion injury (MI/RI) because of its definite inhibition to the opening of mitochondrial permeability transition pore (mPTP). However, the application of cyclosporin A to treat MI/RI is limited due to its immunosuppressive effect to other normal organ and tissues. SS31 represents a novel mitochondria-targeted peptide which can guide drug to accumulate into mitochondria. In this paper, mitochondria-targeted nanoparticles (CsA@PLGA-PEG-SS31) were prepared to precisely deliver cyclosporin A into mitochondria of ischemic cardiomyocytes to treat MI/RI.ResultsCsA@PLGA-PEG-SS31 was prepared by nanoprecipitation. CsA@PLGA-PEG-SS31 showed small particle size (~ 50 nm) and positive charge due to the modification of SS31 on the surface of nanoparticles. CsA@PLGA-PEG-SS31 was stable for more than 30 days and displayed a biphasic drug release pattern. The in vitro results showed that the intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced in hypoxia reoxygenation (H/R) injured H9c2 cells. CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species. In vivo results showed that CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium of MI/RI rat heart. Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function. Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats.ConclusionCsA@PLGA-PEG-SS31 exhibited significant cardioprotective effects against MI/RI in rats hearts through protecting mitochondrial integrity, decreasing apoptosis of cardiomyocytes and myocardial infract area. Thus, CsA@PLGA-PEG-SS31 offered a promising therapeutic method for patients with acute myocardial infarction.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study13

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone13

In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Elamipretide (SS-31).

01AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Pharmacokinetics
In rats with myocardial ischemia reperfusion injury, CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium.
In plain wordsIn rats with heart injury, the SS31-coated cyclosporin A nanoparticles built up in the injured heart muscle.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseAccumulation in ischemic myocardium
Study
ratn: not reported in source
Myocardial ischemia reperfusion injury (MI/RI)
Outcome group
Pharmacokinetics · Cardiovascular
Source sentences
Summary
In vivo results showed that CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium of MI/RI rat heart.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311007
02AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial ischemia reperfusion injury, CsA@PLGA-PEG-SS31 alleviated cardiomyocyte apoptosis.
In plain wordsIn rats with heart injury, the SS31-coated cyclosporin A nanoparticles reduced heart cell death.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCardiomyocyte apoptosis
Study
ratn: not reported in source
Myocardial ischemia reperfusion injury (MI/RI)
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311008
03AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial ischemia reperfusion injury, CsA@PLGA-PEG-SS31 resulted in myocardial salvage.
In plain wordsIn rats with heart injury, the SS31-coated cyclosporin A nanoparticles saved more heart muscle.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMyocardial salvage
Study
ratn: not reported in source
Myocardial ischemia reperfusion injury (MI/RI)
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311009
04AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial ischemia reperfusion injury, CsA@PLGA-PEG-SS31 improved cardiac function.
In plain wordsIn rats with heart injury, the SS31-coated cyclosporin A nanoparticles improved heart function.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseCardiac function
Study
ratn: not reported in source
Myocardial ischemia reperfusion injury (MI/RI)
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311010
05AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial ischemia reperfusion injury, CsA@PLGA-PEG-SS31 reduced the recruitment of inflammatory cells.
In plain wordsIn rats with heart injury, the SS31-coated cyclosporin A nanoparticles reduced the arrival of inflammatory cells in the heart.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseInflammatory cell recruitment to myocardium
Study
ratn: not reported in source
Myocardial ischemia reperfusion injury (MI/RI)
Outcome group
Inflammation markers · Cardiovascular
Source sentences
Summary
Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311011
06AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial ischemia reperfusion injury, CsA@PLGA-PEG-SS31 maintained the integrity of mitochondrial function.
In plain wordsIn rats with heart injury, the SS31-coated cyclosporin A nanoparticles helped keep mitochondrial function intact.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial function integrity in myocardium
Study
ratn: not reported in source
Myocardial ischemia reperfusion injury (MI/RI)
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311012
07AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial ischemia reperfusion injury, CsA@PLGA-PEG-SS31 decreased the myocardial infarct area.
In plain wordsIn rats with heart injury, the SS31-coated cyclosporin A nanoparticles reduced the size of the damaged area.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMyocardial infarct area
Study
ratn: not reported in source
Myocardial ischemia reperfusion injury (MI/RI)
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
CsA@PLGA-PEG-SS31 exhibited significant cardioprotective effects against MI/RI in rats hearts through protecting mitochondrial integrity, decreasing apoptosis of cardiomyocytes and myocardial infract area.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311013
08LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Pharmacokinetics
In hypoxia-reoxygenation injured H9c2 cells, intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced.
In plain wordsIn injured heart cells in the lab, cells took up the SS31-coated cyclosporin A nanoparticles much more.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseIntracellular uptake in H/R injured H9c2 cells
Study
ratn: not reported in source
H9c2 cells with hypoxia reoxygenation injury
Outcome group
Pharmacokinetics · Cardiovascular
Source sentences
Summary
The in vitro results showed that the intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced in hypoxia reoxygenation (H/R) injured H9c2 cells.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311003
09LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Efficacy outcome
In hypoxia-reoxygenation injured H9c2 cells, CsA@PLGA-PEG-SS31 increased cell viability.
In plain wordsIn injured heart cells in the lab, the SS31-coated cyclosporin A nanoparticles raised cell survival.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseViability of H/R injured H9c2 cells
Study
ratn: not reported in source
H9c2 cells with hypoxia reoxygenation injury
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311004
10LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Mechanism
In hypoxia-reoxygenation injured H9c2 cells, CsA@PLGA-PEG-SS31 inhibited opening of the mitochondrial permeability transition pore.
In plain wordsIn injured heart cells in the lab, the SS31-coated nanoparticles reduced opening of a damaging mitochondrial pore.
Peptide
Elamipretide (SS-31)
Outcome
DecreasemPTP opening in H/R injured H9c2 cells
Study
ratn: not reported in source
H9c2 cells with hypoxia reoxygenation injury
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311005
11LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Mechanism
In hypoxia-reoxygenation injured H9c2 cells, CsA@PLGA-PEG-SS31 inhibited production of reactive oxygen species.
In plain wordsIn injured heart cells in the lab, the SS31-coated nanoparticles reduced reactive oxygen species.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseROS production in H/R injured H9c2 cells
Study
ratn: not reported in source
H9c2 cells with hypoxia reoxygenation injury
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311006
12LabNot a test of Elamipretide (SS-31) aloneIn vitro (cell-free)Other
The CsA@PLGA-PEG-SS31 nanoparticles had a small particle size and positive charge.
In plain wordsIn lab tests, the SS31-coated cyclosporin A nanoparticles were small and positively charged.
Peptide
Elamipretide (SS-31)
Outcome
Not applicableParticle size and charge of CsA@PLGA-PEG-SS31
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Particle size
≈ 50 nm
CsA@PLGA-PEG-SS31
Source sentences
Summary
CsA@PLGA-PEG-SS31 showed small particle size (~ 50 nm) and positive charge due to the modification of SS31 on the surface of nanoparticles.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311001
13LabNot a test of Elamipretide (SS-31) aloneIn vitro (cell-free)Other
CsA@PLGA-PEG-SS31 was stable for more than 30 days and showed a biphasic drug release pattern.
In plain wordsIn lab tests, the SS31-coated cyclosporin A nanoparticles stayed stable for over 30 days and released drug in two phases.
Peptide
Elamipretide (SS-31)
Outcome
Not applicableNanoparticle stability and release
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Stability
> 30 days
CsA@PLGA-PEG-SS31
Source sentences
Summary
CsA@PLGA-PEG-SS31 was stable for more than 30 days and displayed a biphasic drug release pattern.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3068311002

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats.

Summary

Results from this study13

Studies that did not test the peptide alone13

Version history

Subjects

Publication types

MeSH terms

Keywords