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


BACKGROUND
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.
Ebrahimnejad
Pedram
P
Novel Drug Delivery Systems Lab, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Dinarvand
Rassoul
R
Sajadi
Abolghasem
A
Jaafari
Mahmoud Reza
MR
Nomani
Ali Reza
AR
Azizi
Ebrahim
E
Rad-Malekshahi
Mazda
M
Atyabi
Fatemeh
F
D002021:Buffers; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005492:Folic Acid / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D019344:Lactic Acid / Q000737:chemistry; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D002021:Buffers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000077146:Irinotecan; D005492:Folic Acid; D002166:Camptothecin