title: Novel isoprenoyl nanoassembled prodrug for paclitaxel delivery.
abstract: A new paclitaxel (Ptx) prodrug was designed by coupling a single terpene unit (MIP) to the hydroxyl group in position 2' of the drug molecule. Using a squalene derivative of polyethylene glycol (SQ-PEG) as surface active agent, the resulting bioconjugate (PtxMIP) self-assembled in water leading to the formation of stable nanoparticles (PtxMIP_SQ-PEG NPs) with an impressively high drug loading (82%). In vivo, the anticancer activity of this novel Ptx nanoassembled prodrug was compared to the conventional Cremophor-containing formulation (Taxol) on a murine model of breast cancer lung metastasis induced by intravenous injection of 4T1 tumor cells, genetically modified to stably express firefly luciferase. Cell growth was assessed noninvasively by bioluminescence imaging (BLI) which enabled monitoring tumor metastatic burden in the same animals. PtxMIP_SQ-PEG nanoparticles slowed metastatic spread and were better tolerated than the Cremophor-containing formulation (i.e., free drug), thus demonstrating the potential of terpene-based nanoassembled prodrugs in the improvement of the therapeutic index of Ptx in balb/c mice.
authors.affiliation: Université Paris-Sud , Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry cedex, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Mura
authors.forename: Fatima
authors.initials: F
authors.lastname: Zouhiri
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lerondel
authors.forename: Andrei
authors.initials: A
authors.lastname: Maksimenko
authors.forename: Julie
authors.initials: J
authors.lastname: Mougin
authors.forename: Claire
authors.initials: C
authors.lastname: Gueutin
authors.forename: Davide
authors.initials: D
authors.lastname: Brambilla
authors.forename: Joachim
authors.initials: J
authors.lastname: Caron
authors.forename: Eric
authors.initials: E
authors.lastname: Sliwinski
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaele
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002070:Butadienes / Q000737:chemistry*; D004195:Disease Models, Animal; D018450:Disease Progression; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005260:Female; D045782:Hemiterpenes / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000378:metabolism* / Q000494:pharmacology; D010420:Pentanes / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002070:Butadienes; D045782:Hemiterpenes; D010420:Pentanes; D011355:Prodrugs; C005059:isoprene; D017239:Paclitaxel