title: SN38 polymeric nanoparticles: in vitro cytotoxicity and in vivo antitumor efficacy in xenograft balb/c model with breast cancer versus irinotecan.
abstract: SN38 (7-ethyl-10-hydroxyl camptothecin), a potent metabolite of irinotecan, has been considered as an anticancer candidate. Its clinical development has been hampered due to its poor solubility. As a result, SN38 loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) was developed in current study to solve its poor water solubility problem while maintaining its cytotoxicity against cancer cells. PLGA NPs were prepared using modified emulsification-solvent evaporation technique and their characteristics were optimized by central composite experimental design in which average size, entrapment efficiency and drug loading were 170.5±11.87 nm, 77.35%±2.314 and 5.95%±0.087, respectively. Scanning electron microscopy and in vitro studies consisting of drug release and cytotoxicity in 4T1 breast cancer cells followed by in vivo biodistribution and blood cytotoxicity were carried out. Therapeutic efficacy of SN38-NPs was evaluated in xenograft balb/c animal with 4T1 breast cancer. The results demonstrated that the treatment with SN38-NPs was more efficacious in comparison with irinotecan. In conclusion, superior cytotoxic effect and improved in vivo antitumor efficacy of SN38-NPs versus irinotecan introduced SN38-NPs as a promising candidate for cancer treatment investigation.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nano Alvand Co., Avicenna Tech. Park, Tehran University of Medical sciences, Tehran, Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Sepehri
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nano Alvand Co., Avicenna Tech. Park, Tehran University of Medical sciences, Tehran, Iran.
authors.forename: Hasti
authors.initials: H
authors.lastname: Rouhani
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Faranak
authors.initials: F
authors.lastname: Tavassolian
authors.affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Montazeri
authors.affiliation: Department of Drug and Food Control, Faculty of Pharmacy and Pharmaceutical Quality Assurance Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khoshayand
authors.affiliation: Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
authors.affiliation: Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dinarvand@tums.ac.ir.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D006801:Humans; D000077146:Irinotecan; D019344:Lactic Acid / Q000737:chemistry*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013499:Surface Properties; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077146:Irinotecan; D002166:Camptothecin
keywords: Anti-tumor efficacy; Cytotoxicity; Irinotecan; PLGA nanoparticles; SN38