title: Long chain lipid based tamoxifen NLC. Part II: pharmacokinetic, biodistribution and in vitro anticancer efficacy studies.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology (Deemed University), Matunga, Mumbai 400019, India.
authors.forename: Harshad
authors.initials: H
authors.lastname: Shete
authors.forename: Sushmita
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Abhijit
authors.initials: A
authors.lastname: De
authors.forename: Vandana
authors.initials: V
authors.lastname: Patravale
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D005434:Flow Cytometry; D006207:Half-Life; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008198:Lymph Nodes / Q000378:metabolism; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D049329:Nanostructures; D036103:Nanotechnology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013629:Tamoxifen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013678:Technology, Pharmaceutical / Q000379:methods; D015854:Up-Regulation
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004965:Estrogen Antagonists; D008055:Lipids; C060192:MUC1 protein, human; D018396:Mucin-1; D013629:Tamoxifen
keywords: Lymphatic system; Nanostructured lipid carriers; Pharmacokinetics; Tamoxifen