title: The ligand (s) anchored lipobrid nanoconstruct mediated delivery of methotrexate: an effective approach in breast cancer therapeutics.
abstract: The present study was designed to engineer surface-anchored and methotrexate loaded lipobrid nano-constructs for targeting breast cancer. Ligands (fucose, galactose and mannose) anchored lipobrid nano-constructs were used to compare and assess delivery efficiency in breast cancer cell lines as well as in DMBA induced breast cancer animal model. The developed and characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, bio-distribution, changes in tumor volume and animal survival. Our results show greater cellular uptake, cytotoxicity at low IC50, apoptosis with altered lysosomal membrane permeability and greater rate of degradation of lysosomal membrane. We saw better bioavailability and tumor targeting efficiency with minimum secondary organ drug distribution. The significant reduction was seen in tumor burden with ligand anchored lipobrids in comparison to plain and MTX-lipobrid formulations. In conclusion, fucose anchored MTX-lipobrid formulation showed promising results, and warrants to explore the development of therapeutic interventions for breast cancer.
authors.affiliation: Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India.
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Garg
authors.affiliation: Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India; UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh, India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar (Mohali), Punjab, India.
authors.forename: Varun
authors.initials: V
authors.lastname: Kushwah
authors.affiliation: Department of Periodontics, College of Dental Medicine Georgia Regents University, Augusta, GA, USA. Electronic address: rajeev.gru@gmail.com.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Tyagi
authors.affiliation: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr H. S. Gour University, Sagar, MP, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar (Mohali), Punjab, India.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.affiliation: Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India. Electronic address: drkatare@yahoo.com.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Katare
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D002470:Cell Survival; D006801:Humans; D008024:Ligands; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage*
chemical_list: D000964:Antimetabolites, Antineoplastic; D008024:Ligands; D008727:Methotrexate
keywords: Breast cancer targeting; Carbohydrate ligands; Lectin receptors; Lipobrids; Methotrexate