Tamoxifen nanostructured lipid carriers: Enhanced in vivo antitumor efficacy with reduced adverse drug effects

• Published in: International journal of pharmaceutics 2014-07, Vol.468 (1-2), p.1-14
• Main Authors: Shete, Harshad K., Selkar, Nilakash, Vanage, Geeta R., Patravale, Vandana B.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - chemistry; Antineoplastic Agents, Hormonal - pharmacokinetics; Antineoplastic Agents, Hormonal - pharmacology; Antineoplastic Agents, Hormonal - toxicity; Biological Availability; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - prevention & control; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Drug Carriers; Female; Hepatotoxicity; Intestinal Absorption; Intestinal lymphatic system; Lipids - chemistry; Mice, Inbred BALB C; Murine model; Nanostructured lipid carriers; Nanostructures; Nanotechnology; Tamoxifen; Tamoxifen - administration & dosage; Tamoxifen - chemistry; Tamoxifen - pharmacokinetics; Tamoxifen - pharmacology; Tamoxifen - toxicity; Technology, Pharmaceutical - methods; Tissue Distribution
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2014.03.056

[Display omitted] 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 3mg/kg Tmx-NLC compared to 3mg/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.