title: Dextran-poly lactide-co-glycolide polymersomes decorated with folate-antennae for targeted delivery of docetaxel to breast adenocarcinima in vitro and in vivo.
abstract: In this study, a tumor-targeted, docetaxel encapsulated dextran-poly lactide-co-glycolide (DEX-PLGA) polymersomes was fabricated for breast cancer chemotherapy. To attain active cancer targeting, docetaxel encapsulated polymersomes was conjugated with folate for folate receptor guided delivery which is overexpressed in various cancer cells including breast adenocarcinoma. Docetaxel was encapsulated in the bilayer of DEX-PLGA or folate-conjugated DEX-PLGA (FA-DEX-PLGA) polymersomes via nanoprecipitation method in order to provide the controlled drug release. The size of polymersomes obtained were 178.53±2.5nm and offered drug encapsulation efficiency and loading content of 78.85±3.81% and 9.32±0.27, respectively. The data demonstrate that the prepared polymersome formulations sustained docetaxel release for a period of 6days. Cellular uptake study and MTT assay showed that the developed folate-targeted docetaxel-loaded polymersomes had higher cytotoxicity than non-targeted ones as well as free form of drug and was accumulated in 4T1 and MCF-7 cells in vitro. The in vivo tumor inhibitory effect of folate-conjugated docetaxel-loaded DEX-PLGA polymersomes (FA-DEX-PLGA-DTX-NPs) demonstrated an increased therapeutic potency of targeted formulation over both non-targeted (DEX-PLGA-DTX-NPs) and free drug. The represented data reveal that the prepared targeted drug delivery system was able to control the docetaxel release, and also enhance the antitumor potency of docetaxel. This study may open new direction for preparation of folate receptor targeted polymersomes based on DEX-PLGA copolymers for translational purposes.
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: alibolandim@mums.ac.ir.
authors.forename: Mona
authors.initials: M
authors.lastname: Alibolandi
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Medicinal Chemistry Department, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Medicinal Chemistry Department, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
authors.affiliation: Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Taghdisi
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Alabdollah
authors.affiliation: Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Mohammadi
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hooriyeh
authors.initials: H
authors.lastname: Nassirli
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D011091:Polyesters / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D004337:Drug Carriers; D011091:Polyesters; D043823:Taxoids; C000625765:dextran-poly(lactide-co-glycolide); D000077143:Docetaxel; D005492:Folic Acid
keywords: DEX-PLGA; Docetaxel; Folate; Polymersome; Targeted drug delivery