Tamoxifen nanostructured lipid carriers: enhanced in vivo antitumor efficacy with reduced adverse drug effects.
A novel approach of enhancing the Tamoxifen uptake via Intestinal Lymphatic System is executed by developing long chain lipid and oil based nanostructured lipid carrier system (Tmx-NLC). The aim was to achieve improved systemic bioavailability of Tamoxifen, prevent systemic and hepatotoxicity and enhance antitumor efficacy. Following the proof of concept achieved in cell culture experiments and in vivo pharmacokinetic and biodistribution study, the current work focuses on investigation of antitumor efficacy and treatment associated toxicity in murine mammary tumor mice model. The efficacy study demonstrated greater tumor suppression and 100% survival with 1.5 and 3 mg/kg Tmx-NLC compared to 3 mg/kg Tamoxifen suspension and Mamofen(®) (Khandelwal Pharmaceuticals, Mumbai, India). Tmx-NLC treatment for a month demonstrated improved systemic toxicity profile and no evidences of hepatotoxicity. Thus, developed Tmx-NLC could prove to be a promising delivery strategy to confer superior therapeutic efficacy and ability to address the biopharmaceutical and toxicity associated issues of drug.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University under Section 3 of UGC Act-1956, Elite Status and Center of Excellence-Government of Maharashtra, Matunga (E), Mumbai, Maharashtra 400019, India.
Harshad K
HK
Shete
National Centre for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health, J.M. Street, Parel, Mumbai, Maharashtra 400012, India.
Nilakash
N
Selkar
National Centre for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health, J.M. Street, Parel, Mumbai, Maharashtra 400012, India. Electronic address: vanageg@nirrh.res.in.
Geeta R
GR
Vanage
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University under Section 3 of UGC Act-1956, Elite Status and Center of Excellence-Government of Maharashtra, Matunga (E), Mumbai, Maharashtra 400019, India. Electronic address: vbp_muict@yahoo.co.in.
Vandana B
VB
Patravale
D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D049329:Nanostructures; D036103:Nanotechnology; D013629:Tamoxifen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
D018931:Antineoplastic Agents, Hormonal; D004337:Drug Carriers; D008055:Lipids; D013629:Tamoxifen
Hepatotoxicity; Intestinal lymphatic system; Murine model; Nanostructured lipid carriers; Tamoxifen