title: Nanomicellar paclitaxel increases cytotoxicity of multidrug resistant breast cancer cells.
abstract: Multidrug resistance (MDR) of breast cancer cells still represents an unmet medical need in chemotherapy. To this end, the purpose of this study was to determine efficacy of paclitaxel loaded in sterically stabilized, biocompatible and biodegradable sterically stabilized mixed phospholipid nanomicelles (SSMM; size, approximately 15 nm) and actively targeted vasoactive intestinal peptide-grafted SSMM (SSMM-VIP) in circumventing P-gp-mediated paclitaxel resistance in BC19/3 cells, a human breast cancer cell line that expresses >10-fold higher P-gp than its parental sensitive cell line, MCF-7. We found that in drug sensitive MCF-7 cells, paclitaxel loaded in SSMM (P-SSMM) and SSMM-VIP (P-SSMM-VIP) significantly inhibited cell growth in dose-dependent fashion (p<0.05). Both formulations were approximately 7-fold more potent than paclitaxel dissolved in DMSO (P-DMSO). Efficacy of P-SSMM and P-SSMM-VIP was similar (p>0.5). By contrast, in drug resistant BC19/3 cells, P-SSMM-VIP was significantly more effective than either P-SSMM or P-DMSO ( approximately 2- and 5-fold, respectively; p<0.05). Collectively, these data indicate that actively targeted paclitaxel-loaded SSMM-VIP overcomes multiple drug resistance of BC19/3 cells. We suggest this formulation should be further developed to treat MDR breast cancer.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, IL 60612-4325, USA.
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyüksel
authors.forename: Eunjung
authors.initials: E
authors.lastname: Jeon
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008823:Micelles; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D017239:Paclitaxel