title: PEGylated chitosan nanoparticles potentiate repurposing of ormeloxifene in breast cancer therapy.
abstract: Development and optimization of ormeloxifene-loaded PEGylated chitosan nanoparticles (CNPs) for enhancing its literature profound therapeutic activity against breast cancer.
  
  
  
  CNPs were prepared by ionotropic gelation method and characterized.
  
  
  
  Optimized formulation (CNPs10) had average 304 nm particle size with 0.247 polydispersity index and spherical shape with +31 mV surface charge. CNPs10 had 88.37% entrapment efficiency and 20.93% loading efficiency. CNPs10 demonstrated dose-dependent enhancement in cytotoxicity, cellular uptake, apoptosis, disruption of mitochondrial membrane potential and activation of caspase-3 in breast cancer MDA-MB-231 and MCF-7 cells over free ormeloxifene. In vivo studies divulged improved pharmacokinetic parameters, reduced toxicity, suppressed tumor burden and increased survival in CNPs10-treated female Sprague-Dawley rats.
  
  
  
  PEGylated CNPs enhanced anticancer activity of ormeloxifene.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Hafsa
authors.initials: H
authors.lastname: Ahmad
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Dwivedi
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Shukla
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Arya
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Komal
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Jawahar
authors.initials: J
authors.lastname: Lal
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives*; D004337:Drug Carriers / Q000737:chemistry*; D058492:Drug Repositioning; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D004337:Drug Carriers; D011092:Polyethylene Glycols; C508548:ormeloxifene; D048271:Chitosan; D053148:Caspase 3
keywords: breast cancer; centchroman; ormeloxifene