title: Codelivery of doxorubicin and paclitaxel by cross-linked multilamellar liposome enables synergistic antitumor activity.
abstract: Combining chemotherapeutics is a promising method of improving cancer treatment; however, the clinical success of combination therapy is limited by the distinct pharmacokinetics of combined drugs, which leads to nonuniform distribution. In this study, we report a new robust approach to load two drugs with different hydrophilicities into a single cross-linked multilamellar liposomal vesicle (cMLV) to precisely control the drug ratio that reaches the tumor in vivo. The stability of cMLVs improves the loading efficiency and sustained release of doxorubicin (Dox) and paclitaxel (PTX), maximizing the combined therapeutic effect and minimizing the systemic toxicity. Furthermore, we show that the cMLV formulation maintains specific drug ratios in vivo for over 24 h, enabling the ratio-dependent combination synergy seen in vitro to translate to in vivo antitumor activity and giving us control over another parameter important to combination therapy. This combinatorial delivery system may provide a new strategy for synergistic delivery of multiple chemotherapeutics with a ratiometric control over encapsulated drugs to treat cancer and other diseases.
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California , Los Angeles, California 90089, United States.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Liu
authors.forename: Jinxu
authors.initials: J
authors.lastname: Fang
authors.forename: Yu-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wong
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D050997:Nanomedicine / Q000379:methods*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D004317:Doxorubicin; D017239:Paclitaxel