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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.
AuthorsNima Sepehri, Hasti Rouhani, Faranak Tavassolian, Hamed Montazeri, Mohammad Reza Khoshayand, Mohammad Hossein Ghahremani, Seyed Nasser Ostad, Fatemeh Atyabi, Rassoul Dinarvand
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 471 Issue 1-2 Pg. 485-97 (Aug 25 2014) ISSN: 1873-3476 [Electronic] Netherlands
PMID24879937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • polylactic acid-polyglycolic acid copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • irinotecan
  • Camptothecin
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacology, therapeutic use)
  • Camptothecin (administration & dosage, analogs & derivatives, chemistry, pharmacology, therapeutic use)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Drug Carriers (chemistry)
  • Drug Liberation
  • Female
  • Humans
  • Lactic Acid (chemistry)
  • Mammary Neoplasms, Experimental (drug therapy, pathology)
  • Mice, Inbred BALB C
  • Nanoparticles (chemistry)
  • Particle Size
  • Polyglycolic Acid (chemistry)
  • Solubility
  • Surface Properties
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

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