Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines.

Abstract

SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan, which is 100-to 1000-fold more cytotoxic than irinotecan. Nevertheless, extreme hydrophobicity of SN-38 has prevented its clinical use. One way of improving the solubility and stability of SN-38 is to formulate the drug into nanoparticles. Folic acid has been widely used as a targeting moiety for various anticancer drugs. For folate-receptor-targeted anticancer therapy, SN-38 nanoparticles were produced using poly-lactide-co-glycolide-polyethylene glycol-folate (PLGA-PEG-FOL) conjugate by emulsification/solvent evaporation method. The FOL-conjugated di-block copolymer was synthesized by coupling the PLGA-PEG-NH(2) di-block copolymer with an activated folic acid. The conjugates were used for the formation of SN-38 nanoparticles with an average size of 200 nm in diameter. The SN-38 targeted nanoparticles showed a greater cytotoxicity against HT-29 cancer cells than SN-38 nontargeted nanoparticles. These results suggested that folate-targeted nanoparticles could be a potentially useful delivery system for SN-38 as an anticancer agent.

FROM THE CLINICAL EDITOR:

SN-38 is the active metabolite of the chemotherapy agent irinotecan, which is 100-1000 fold more cytotoxic than irinotecan, but its extreme hydrophobicity has prevented its clinical use. In this paper, the authors present a nanotechnology-based approach targeting the folate-receptor with SN-38 loaded nanoparticles, demonstrating stronger cytotoxicity against HT-29 cancer cells than with control nanoparticles.

• Authors: Pedram Ebrahimnejad, Rassoul Dinarvand, Abolghasem Sajadi, Mahmoud Reza Jaafari, Ali Reza Nomani, Ebrahim Azizi, Mazda Rad-Malekshahi, Fatemeh Atyabi
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 6 Issue 3 Pg. 478-85 (Jun 2010) ISSN: 1549-9642 [Electronic] United States
• PMID: 19836467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Buffers
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Polyethylene Glycols
• Irinotecan
• Folic Acid
• Camptothecin

Topics

• Buffers
• Camptothecin (analogs & derivatives, chemistry, pharmacology)
• Cell Death (drug effects)
• Drug Delivery Systems (methods)
• Folic Acid (chemistry)
• HT29 Cells
• Humans
• Irinotecan
• Lactic Acid (chemistry)
• Microscopy, Fluorescence
• Nanoparticles (chemistry, ultrastructure)
• Polyethylene Glycols (chemistry)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer