title: Novel diindolylmethane derivatives based NLC formulations to improve the oral bioavailability and anticancer effects in triple negative breast cancer.
abstract: The present study demonstrates the promising anticancer effects of novel C-substituted diindolylmethane (DIM) derivatives DIM-10 and DIM-14 in aggressive TNBC models. In vitro studies demonstrated that these compounds possess strong anticancer effects. Caco-2 permeability studies resulted in poor permeability and poor oral bioavailability was demonstrated by pharmacokinetic studies. Nano structured lipid carrier (NLC) formulations were prepared to increase the clinical acceptance of these compounds. Significant increase in oral bioavailability was observed with NLC formulations. Compared to DIM-10, DIM-10 NLC formulation showed increase in Cmaxand AUC values by 4.73 and 11.19-folds, respectively. Similar pattern of increase was observed with DIM-14 NLC formulations. In dogs DIM-10 NLC formulations showed an increase of 2.65 and 2.94-fold in Cmaxand AUC, respectively. The anticancer studies in MDA-MB-231 orthotopic TNBC models demonstrated significant reduction in tumor volumes in DIM-10 and DIM-14 NLC treated animals. Our studies suggest that NLC formulation of both DIM-10 and 14 is effective in TNBC models.
authors: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana 500037, India.
authors: Chandraiah
authors: C
authors: Godugu
authors: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
authors: Ravi
authors: R
authors: Doddapaneni
authors: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
authors: Stephen H
authors: SH
authors: Safe
authors: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA. Electronic address: mandip.sachdeva@gmail.com.
authors: Mandip
authors: M
authors: Singh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D019540:Area Under Curve; D001682:Biological Availability; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D007211:Indoles; D008055:Lipids; C016392:3,3'-diindolylmethane
keywords: Diindolylmethane; Nano structured lipid carriers; Oral bioavailability; Triple negative breast cancer (TNBC)