PMID- 32778980
OWN - NLM
STAT- MEDLINE
DCOM- 20201014
LR  - 20221207
IS  - 1530-9932 (Electronic)
IS  - 1530-9932 (Linking)
VI  - 21
IP  - 6
DP  - 2020 Aug 10
TI  - Development and In Vitro Evaluation of Long Circulating Liposomes for Targeted 
      Delivery of Gemcitabine and Irinotecan in Pancreatic Ductal Adenocarcinoma.
PG  - 231
LID - 10.1208/s12249-020-01745-6 [doi]
AB  - The classically used nontargeted chemotherapeutic approach to pancreatic cancer 
      has a dual drawback of suboptimal drug delivery at the target site and the 
      systemic side effects produced by the unfettered exposure of the drug to healthy 
      tissue. This study has the objective of developing novel 
      poly(2-ethyl-2-oxazoline) (PETOX)-based long circulating liposomes loaded with 
      gemcitabine and irinotecan for the treatment of pancreatic ductal adenocarcinoma, 
      with a juxtaposition to PEGylated and uncoated liposomes. A PETOX-cholesteryl 
      chloroformate lipopolymer conjugate (PETOX-ChC) with a carbonate linkage was 
      prepared and characterized by (1)H NMR, FTIR, and DSC. Liposomes were prepared 
      using the thin film hydration technique followed by freeze-thaw and membrane 
      extrusion methods. Liposome characterization includes particle size 
      determination, zeta potential determination using a zetameter, and structural 
      elucidation using (31)P NMR and cryo-TEM. The PETOXylated liposomes showed a 
      particle size of 180.1 +/- 2.2 nm and a zeta potential of - 33.63 +/- 1.23 mV. The 
      liposomal combination therapy of gemcitabine and irinotecan was found to have an 
      IC(50) value 39 times lower in comparison to the drug combination in solution, 
      while the PEGylated and PETOXylated liposomes showed IC(50) values 1.6 times 
      lower and 2 times lower than that of uncoated liposomes, respectively, against 
      Mia PaCa II pancreatic cancer cell line. The PEGylated and PETOXylated liposomes 
      showed 4.1 and 5.4 times slower macrophagial uptake in vitro in comparison to the 
      uncoated liposomes respectively. The PEGylated liposomes showed 11% higher in 
      vitro macrophagial uptake in comparison to PETOXylated liposomes.
FAU - Deodhar, S
AU  - Deodhar S
AD  - Department of Pharmacy Sciences, School of Pharmacy and Health Professions, 
      Creighton University, 2500 California Plaza, Omaha, Nebraska, 68178, USA.
FAU - Dash, A K
AU  - Dash AK
AD  - Department of Pharmacy Sciences, School of Pharmacy and Health Professions, 
      Creighton University, 2500 California Plaza, Omaha, Nebraska, 68178, USA. 
      adash@creighton.edu.
FAU - North, E J
AU  - North EJ
AD  - Department of Pharmacy Sciences, School of Pharmacy and Health Professions, 
      Creighton University, 2500 California Plaza, Omaha, Nebraska, 68178, USA.
FAU - Hulce, M
AU  - Hulce M
AD  - Department of Chemistry, Creighton University, Omaha, Nebraska, USA.
LA  - eng
PT  - Journal Article
DEP - 20200810
PL  - United States
TA  - AAPS PharmSciTech
JT  - AAPS PharmSciTech
JID - 100960111
RN  - 0 (Liposomes)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 7673326042 (Irinotecan)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Adenocarcinoma/*drug therapy
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Carcinoma, Pancreatic Ductal/*drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Deoxycytidine/administration & dosage/*analogs & derivatives
MH  - Drug Delivery Systems
MH  - Humans
MH  - Irinotecan/*administration & dosage
MH  - *Liposomes
MH  - Pancreatic Neoplasms/*drug therapy/pathology
MH  - Particle Size
MH  - Polyethylene Glycols/chemistry
MH  - Gemcitabine
OTO - NOTNLM
OT  - gemcitabine
OT  - irinotecan
OT  - long circulating liposome
OT  - pancreatic cancer
OT  - polyethylene glycol
OT  - polyoxazoline
EDAT- 2020/08/12 06:00
MHDA- 2020/10/21 06:00
CRDT- 2020/08/12 06:00
PHST- 2020/04/07 00:00 [received]
PHST- 2020/07/05 00:00 [accepted]
PHST- 2020/08/12 06:00 [entrez]
PHST- 2020/08/12 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
AID - 10.1208/s12249-020-01745-6 [pii]
AID - 10.1208/s12249-020-01745-6 [doi]
PST - epublish
SO  - AAPS PharmSciTech. 2020 Aug 10;21(6):231. doi: 10.1208/s12249-020-01745-6.