A microemulsion co-loaded with Schizandrin A-docetaxel enhances esophageal carcinoma treatment through overcoming multidrug resistance.
Multidrug resistance (MDR) is the major underlying cause of the low 5-year survival rate of esophageal carcinoma. In this study, we developed a novel microemulsion system (SD-ME) co-loaded with docetaxel (DTX) and Schizandrin A, a potent chemotherapeutic agent and a potential drug resistance modulator, respectively. In the physicochemical characterization studies, SD-ME displayed a well-defined spherical shape and size (56.62 ± 4.16 nm), a narrow polydispersity index (PDI, 0.132 ± 0.002), and a negative surface charge (-19.81 ± 3.11 mv). In the cellular uptake studies, SD-ME with a DTX concentration of 30 μg/mL exhibited a 3.9-fold enhancement of DTX internalization in DTX-resistant EC109 (EC109/DDR) cells in comparison to that observed for EC109 cells, and the mechanisms were associated with reducing P-gp expression and inhibiting P-gp ATPease. The half-maximal inhibitory concentrations (IC50) of DTX and SD-ME against EC109/DDR cells were 40.57 ± 0.39 and 3.59 ± 0.06 μg/mL, respectively. Likewise, the apoptotic rate of EC109/DDR treated with SD-ME increased up to 20-fold compared to that observed with free DTX. In anticancer efficacy studies in vivo, SD-ME markedly retarded the tumor growth of nude mice bearing EC109/DDR tumor xenografts compared with D-ME and free DTX throughout the duration of study. Consequently, mice treated with SD-ME had the highest survival rate (37.5%) during the observation period (70 days). In addition, there were no apparent side effects after the administration of SD-ME. Overall, our study provides evidence for SD-ME as an effective drug delivery system for enhanced MDR tumor treatment.
a Department of Oncology , Zhongda Hospital, School of Medicine, Southeast University , Nanjing , P.R. China.
Xiangyu
X
Su
a Department of Oncology , Zhongda Hospital, School of Medicine, Southeast University , Nanjing , P.R. China.
Chanchan
C
Gao
a Department of Oncology , Zhongda Hospital, School of Medicine, Southeast University , Nanjing , P.R. China.
Fangfang
F
Shi
a Department of Oncology , Zhongda Hospital, School of Medicine, Southeast University , Nanjing , P.R. China.
Xiaoyao
X
Feng
a Department of Oncology , Zhongda Hospital, School of Medicine, Southeast University , Nanjing , P.R. China.
Lin
L
Liu
b Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , P.R. China , and.|c Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing , P.R. China.
Ding
D
Qu
a Department of Oncology , Zhongda Hospital, School of Medicine, Southeast University , Nanjing , P.R. China.
Cailian
C
Wang
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D034242:Cyclooctanes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004339:Drug Compounding; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004655:Emulsions; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010316:Particle Size; D011083:Polycyclic Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D034242:Cyclooctanes; D004338:Drug Combinations; D004655:Emulsions; D017705:Lignans; D011083:Polycyclic Compounds; D043823:Taxoids; D000077143:Docetaxel; C034734:schizandrin A
Docetaxel; Schizandrin A; drug resistance; esophageal carcinoma; microemulsion