TY - JOUR
T1 - Long chain lipid based tamoxifen NLC. Part II
T2 - Pharmacokinetic, biodistribution and in vitro anticancer efficacy studies
AU - Shete, Harshad
AU - Chatterjee, Sushmita
AU - De, Abhijit
AU - Patravale, Vandana
N1 - Funding Information:
Authors are thankful to University Grant Commission (UGS-SAP) (ICT) and ICMR (ACTREC), Government of India, New Delhi, India for providing financial assistance. The authors are also thankful to Khandelwal Pharmaceuticals Pvt. Ltd. (Mumbai, India) for providing drug sample, Abitec Corporation (Janesville, USA), BASF Fine Chemicals (Mumbai, India), Gattefosse (St-Priest, France) and Sasol GmbH (Hamburg, Germany) for providing gift samples of various excipients. The authors wish to thank Dr. Yogita Pawar BARC, Mumbai, India for their help in identifying and excision of mesenteric lymph nodes in rats.
PY - 2013
Y1 - 2013
N2 - Long chain lipid (LCL) based tamoxifen loaded nanostructured lipid carriers (Tmx-NLCs) meant to target intestinal lymphatic systems (ILSs) was developed and characterized previously. The aim of the present work was to evaluate in vitro efficacy of developed Tmx-NLC against breast cancer cell lines and to confirm the hypothesis of targeting ILS after single dose oral administration. In vitro anticancer activity of Tmx-NLC was assessed in human estrogen receptor expressing breast cancer cell lines viz. MCF-7 and ZR-75-1. The study revealed relatively improved activity for Tmx-NLC compared to free Tmx against MCF-7 cells. However, the activity was compromised against ZR-75-1 cells which could be attributed to its up regulation of MUC1 gene. Confocal and flow cytometric analysis revealed remarkable intracellular uptake of Tmx-NLC and its localization in nuclear and perinuclear region of cells. Tmx-NLC exhibited distinctly different pharmacokinetic profile compared to Tamoxifen suspension (Tmx-susp) and exhibited an increment in the bioavailability by 2.71-fold and prolonged the T1/2 by 7.10-fold. Moreover, detectable drug concentration in mesenteric lymph nodes justifies our hypothesis of targeting ILS and explains the major uptake of Tmx to occur via lymphatic system.
AB - Long chain lipid (LCL) based tamoxifen loaded nanostructured lipid carriers (Tmx-NLCs) meant to target intestinal lymphatic systems (ILSs) was developed and characterized previously. The aim of the present work was to evaluate in vitro efficacy of developed Tmx-NLC against breast cancer cell lines and to confirm the hypothesis of targeting ILS after single dose oral administration. In vitro anticancer activity of Tmx-NLC was assessed in human estrogen receptor expressing breast cancer cell lines viz. MCF-7 and ZR-75-1. The study revealed relatively improved activity for Tmx-NLC compared to free Tmx against MCF-7 cells. However, the activity was compromised against ZR-75-1 cells which could be attributed to its up regulation of MUC1 gene. Confocal and flow cytometric analysis revealed remarkable intracellular uptake of Tmx-NLC and its localization in nuclear and perinuclear region of cells. Tmx-NLC exhibited distinctly different pharmacokinetic profile compared to Tamoxifen suspension (Tmx-susp) and exhibited an increment in the bioavailability by 2.71-fold and prolonged the T1/2 by 7.10-fold. Moreover, detectable drug concentration in mesenteric lymph nodes justifies our hypothesis of targeting ILS and explains the major uptake of Tmx to occur via lymphatic system.
KW - Lymphatic system
KW - Nanostructured lipid carriers
KW - Pharmacokinetics
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=84884156746&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2013.03.036
DO - 10.1016/j.ijpharm.2013.03.036
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:84884156746
SN - 0378-5173
VL - 454
SP - 584
EP - 592
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1
ER -
