PMID- 34324983
OWN - NLM
STAT- MEDLINE
DCOM- 20210922
LR  - 20240403
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Print)
IS  - 0378-5173 (Linking)
VI  - 607
DP  - 2021 Sep 25
TI  - Cannabidiol loaded extracellular vesicles sensitize triple-negative breast cancer 
      to doxorubicin in both in-vitro and in vivo models.
PG  - 120943
LID - S0378-5173(21)00749-3 [pii]
LID - 10.1016/j.ijpharm.2021.120943 [doi]
AB  - Extracellular Vesicles (EVs) were isolated from human umbilical cord mesenchymal 
      stem cells (hUCMSCs) and were further encapsulated with cannabidiol (CBD) through 
      sonication method (CBD EVs). CBD EVs displayed an average particle size of 
      114.1 +/- 1.02 nm, zeta potential of -30.26 +/- 0.12 mV, entrapment efficiency of 
      92.3 +/- 2.21% and stability for several months at 4  degrees C. CBD release from the EVs 
      was observed as 50.74 +/- 2.44% and 53.99 +/- 1.4% at pH 6.8 and pH 7.4, respectively 
      after 48 h. Our in-vitro studies demonstrated that CBD either alone or in EVs 
      form significantly sensitized MDA-MB-231 cells to doxorubicin (DOX) (*P < 0.05). 
      Flow cytometry and migration studies revealed that CBD EVs either alone or in 
      combination with DOX induced G1 phase cell cycle arrest and decreased migration 
      of MDA-MB-231 cells, respectively. CBD EVs and DOX combination significantly 
      reduced tumor burden (***P < 0.001) in MDA-MB-231 xenograft tumor model. Western 
      blotting and immunocytochemical analysis demonstrated that CBD EVs and DOX 
      combination decreased the expression of proteins involved in inflammation, 
      metastasis and increased the expression of proteins involved in apoptosis. CBD 
      EVs and DOX combination will have profound clinical significance in not only 
      decreasing the side effects but also increasing the therapeutic efficacy of DOX 
      in TNBC.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Patel, Nilkumar
AU  - Patel N
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, USA.
FAU - Kommineni, Nagavendra
AU  - Kommineni N
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, USA.
FAU - Surapaneni, Sunil Kumar
AU  - Surapaneni SK
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, USA.
FAU - Kalvala, Anil
AU  - Kalvala A
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, USA.
FAU - Yaun, Xuegang
AU  - Yaun X
AD  - Department of Chemical and Biomedical Engineering, Florida State University, 
      Tallahassee, FL, USA; The National High Magnetic Field Laboratory, Florida State 
      University, Tallahassee, FL, USA.
FAU - Gebeyehu, Aragaw
AU  - Gebeyehu A
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, USA.
FAU - Arthur, Peggy
AU  - Arthur P
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, USA.
FAU - Duke, Leanne C
AU  - Duke LC
AD  - Department of Biomedical Sciences, Florida State University College of Medicine, 
      1115 West Call Street, Tallahassee, FL, USA.
FAU - York, Sara B
AU  - York SB
AD  - Department of Biomedical Sciences, Florida State University College of Medicine, 
      1115 West Call Street, Tallahassee, FL, USA.
FAU - Bagde, Arvind
AU  - Bagde A
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, USA.
FAU - Meckes, David G Jr
AU  - Meckes DG Jr
AD  - Department of Biomedical Sciences, Florida State University College of Medicine, 
      1115 West Call Street, Tallahassee, FL, USA.
FAU - Singh, Mandip
AU  - Singh M
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, USA. Electronic address: mandip.sachdeva@gmail.com.
LA  - eng
GR  - U54 MD007582/MD/NIMHD NIH HHS/United States
PT  - Journal Article
DEP - 20210727
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 19GBJ60SN5 (Cannabidiol)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - *Breast Neoplasms/drug therapy
MH  - *Cannabidiol
MH  - Cell Line, Tumor
MH  - Doxorubicin
MH  - *Extracellular Vesicles
MH  - Female
MH  - Humans
MH  - *Triple Negative Breast Neoplasms/drug therapy
PMC - PMC8528640
MID - NIHMS1739672
OTO - NOTNLM
OT  - Cannabidiol
OT  - Doxorubicin and triple negative breast cancer
OT  - Extracellular vesicles
OT  - Sensitization
COIS- Declaration of Competing Interest The authors confirm that there are no competing 
      interests. Declaration of interests The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/07/30 06:00
MHDA- 2021/09/23 06:00
PMCR- 2022/09/25
CRDT- 2021/07/29 20:13
PHST- 2021/05/03 00:00 [received]
PHST- 2021/07/19 00:00 [revised]
PHST- 2021/07/22 00:00 [accepted]
PHST- 2021/07/30 06:00 [pubmed]
PHST- 2021/09/23 06:00 [medline]
PHST- 2021/07/29 20:13 [entrez]
PHST- 2022/09/25 00:00 [pmc-release]
AID - S0378-5173(21)00749-3 [pii]
AID - 10.1016/j.ijpharm.2021.120943 [doi]
PST - ppublish
SO  - Int J Pharm. 2021 Sep 25;607:120943. doi: 10.1016/j.ijpharm.2021.120943. Epub 
      2021 Jul 27.