title: A novel injectable phospholipid gel co-loaded with doxorubicin and bromotetrandrine for resistant breast cancer treatment by intratumoral injection.
abstract: Systemically administered anticancer treatments were greatly limited by extensive side effects mainly due to nonspecific distributions in vivo, and multidrug resistance in various tumors. A phospholipids-based in situ-forming gel platform has been developed for the concurrent delivery of doxorubicin (DOX) and bromotetrandrin (W198). Phospholipid gel containing DOX and W198 remained in a solution (sol) state before injection and underwent rapid gelation after injection in vivo. The release of DOX and W198 from phospholipid gel (PG) was sustained in vitro for over 20 days (d). DOX and W198 from PG achieved prolonged release for over two weeks in rats via subcutaneous injection. Compared with repeated injections of free drug, eliminated cardiac toxicity and less bone marrow inhibition were observed for DOX and W198-loaded PG (DOX/W198-PG) in normal rats via subcutaneous injection. Also, a single intratumoral injection of DOX/W198-PG in the resistant MCF-7/Adr xenograft-bearing mice showed much better antitumor efficacy compared to other treatment groups. In sum, DOX/W198-PG was well demonstrated to achieve sustained drug release both in vitro and in vivo with eliminated toxicity and improved antitumor efficacy by reversing the multidrug resistance in breast cancers.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Luo
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Cao
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China. Electronic address: gongtaoy@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019540:Area Under Curve; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D015552:Injections, Intralesional; D061986:MCF-7 Cells; D008297:Male; D008657:Metabolic Clearance Rate; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010743:Phospholipids / Q000737:chemistry*; D017208:Rats, Wistar; D016896:Treatment Outcome; D014783:Viscosity; D023041:Xenograft Model Antitumor Assays
chemical_list: D044182:Benzylisoquinolines; D010743:Phospholipids; C514835:bromotetrandrine; D004317:Doxorubicin
keywords: Bromotetrandrin; Doxorubicin; In situ-forming gel; Intratumoral injection; Resistant cancer