PMID- 36670992
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230308
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 12
IP  - 1
DP  - 2023 Jan 5
TI  - Curcumin and N-Acetylcysteine Nanocarriers Alone or Combined with Deferoxamine 
      Target the Mitochondria and Protect against Neurotoxicity and Oxidative Stress in 
      a Co-Culture Model of Parkinson's Disease.
LID - 10.3390/antiox12010130 [doi]
LID - 130
AB  - As the blood-brain barrier (BBB) prevents most compounds from entering the brain, 
      nanocarrier delivery systems are frequently being explored to potentially enhance 
      the passage of drugs due to their nanometer sizes and functional characteristics. 
      This study aims to investigate whether Pluronic(R) F68 (P68) and dequalinium (DQA) 
      nanocarriers can improve the ability of curcumin, n-acetylcysteine (NAC) and/or 
      deferoxamine (DFO), to access the brain, specifically target mitochondria and 
      protect against rotenone by evaluating their effects in a combined Transwell(R) 
      hCMEC/D3 BBB and SH-SY5Y based cellular Parkinson's disease (PD) model. P68 + DQA 
      nanoformulations enhanced the mean passage across the BBB model of curcumin, NAC 
      and DFO by 49%, 28% and 49%, respectively (p < 0.01, n = 6). Live cell 
      mitochondrial staining analysis showed consistent co-location of the nanocarriers 
      within the mitochondria. P68 + DQA nanocarriers also increased the ability of 
      curcumin and NAC, alone or combined with DFO, to protect against rotenone induced 
      cytotoxicity and oxidative stress by up to 19% and 14% (p < 0.01, n = 6), as 
      measured by the MTT and mitochondrial hydroxyl radical assays respectively. These 
      results indicate that the P68 + DQA nanocarriers were successful at enhancing the 
      protective effects of curcumin, NAC and/or DFO by increasing the brain penetrance 
      and targeted delivery of the associated bioactives to the mitochondria in this 
      model. This study thus emphasises the potential effectiveness of this nanocarrier 
      strategy in fully utilising the therapeutic benefit of these antioxidants and 
      lays the foundation for further studies in more advanced models of PD.
FAU - Mursaleen, Leah
AU  - Mursaleen L
AD  - Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 
      115 New Cavendish Street, London W1W 6UW, UK.
AD  - Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, 
      London WC1N 1AX, UK.
AD  - Cure Parkinson's Trust, 120 New Cavendish Street, Fitzrovia, London W1W 6XX, UK.
FAU - Chan, Stefanie Ho Yi
AU  - Chan SHY
AUID- ORCID: 0000-0002-1912-3081
AD  - Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 
      115 New Cavendish Street, London W1W 6UW, UK.
AD  - Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, 
      London WC1N 1AX, UK.
FAU - Noble, Brendon
AU  - Noble B
AD  - Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 
      115 New Cavendish Street, London W1W 6UW, UK.
FAU - Somavarapu, Satyanarayana
AU  - Somavarapu S
AD  - Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, 
      London WC1N 1AX, UK.
FAU - Zariwala, Mohammed Gulrez
AU  - Zariwala MG
AUID- ORCID: 0000-0001-9944-8451
AD  - Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 
      115 New Cavendish Street, London W1W 6UW, UK.
LA  - eng
PT  - Journal Article
DEP - 20230105
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC9855117
OTO - NOTNLM
OT  - Parkinson's disease
OT  - SH-SY5Y cells
OT  - Transwell(R) model
OT  - blood-brain barrier
OT  - curcumin
OT  - deferoxamine
OT  - hCMEC/D3
OT  - iron
OT  - n-acetylcysteine
OT  - neurodegeneration
OT  - oxidative stress
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/22 06:01
PMCR- 2023/01/05
CRDT- 2023/01/21 01:04
PHST- 2022/12/07 00:00 [received]
PHST- 2022/12/26 00:00 [revised]
PHST- 2022/12/28 00:00 [accepted]
PHST- 2023/01/21 01:04 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/22 06:01 [medline]
PHST- 2023/01/05 00:00 [pmc-release]
AID - antiox12010130 [pii]
AID - antioxidants-12-00130 [pii]
AID - 10.3390/antiox12010130 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2023 Jan 5;12(1):130. doi: 10.3390/antiox12010130.