Pharmacokinetics and Anti-Tumor Efficacy of PEGylated Liposomes Co-Loaded with Cisplatin and Mifepristone

被引:4
作者
Ocana-Arakachi, Karen [1 ,2 ]
Martinez-Herculano, Julio [1 ]
Jurado, Rafael [1 ]
Llaguno-Munive, Monserrat [1 ,3 ]
Garcia-Lopez, Patricia [1 ]
机构
[1] Inst Nacl Cancerol, Lab Farmaco Oncol, Subdirecc Invest Bas, Mexico City 14080, Mexico
[2] Univ Nacl Autonoma Mexico, Posgrad Ciencias Biol, Mexico City 04510, Mexico
[3] Inst Nacl Cancerol, Lab Fis Med, Subdirecc Invest Basica, Mexico City 14080, Mexico
关键词
bioavailability; cisplatin; co-encapsulation; liposomes; mifepristone; pharmacokinetics; synergism; IN-VITRO; NANOPARTICLES; DELIVERY; CELLS;
D O I
10.3390/ph16101337
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Although cisplatin is an effective chemotherapy drug used against many types of cancer, it has poor bioavailability, produces severe adverse effects, and frequently leads to tumor resistance. Consequently, more effective formulations are needed. The co-administration of cisplatin with mifepristone, which counters an efflux pump drug-resistance mechanism in tumor cells, has shown important synergism, but without resolving the problem of poor bioavailability. Specificity to tumor tissue and bioavailability have been improved by co-encapsulating cisplatin and mifepristone in a liposomal formulation (L-Cis/MF), which needs further research to complete pre-clinical requirements. The aim of this current contribution was to conduct a pharmacokinetic study of cisplatin and mifepristone in male Wistar rats after administration of L-Cis/MF and the conventional (unencapsulated) formulation. Additionally, the capacity of L-Cis/MF to reduce tumor growth in male nude mice was evaluated following the implantation of xenografts of non-small-cell lung cancer. The better pharmacokinetics (higher plasma concentration) of cisplatin and mifepristone when injected in the liposomal versus the conventional formulation correlated with greater efficacy in controlling tumor growth. Future research on L-Cis/MF will characterize its molecular mechanisms and apply it to other types of cancer affected by the synergism of cisplatin and mifepristone.
引用
收藏
页数:16
相关论文
共 41 条
  • [21] Use of an orthovoltage X-ray treatment unit as a radiation research system in a small-animal cancer model
    Medina, Luis-Alberto
    Herrera-Penilla, Blanca-Ivone
    Castro-Morales, Mario-Alberto
    Garcia-Lopez, Patricia
    Jurado, Rafael
    Perez-Cardenas, Enrique
    Chanona-Vilchis, Jose
    Brandan, Maria-Ester
    [J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2008, 27 (1)
  • [22] Multicompartimental Nanoparticles for Co-Encapsulation and Multimodal Drug Delivery to Tumor Cells and Neovasculature
    Mendes, Livia Palmerston
    Nogueira Gaeti, Marilisa Pedroso
    Marcelino de Avila, Paulo Henrique
    Vieira, Marcelo de Sousa
    Rodrigues, Bruna dos Santos
    de Avila Marcelino, Renato Ivan
    Rosa dos Santos, Lilian Cristina
    Valadares, Marize Campos
    Lima, Eliana Martins
    [J]. PHARMACEUTICAL RESEARCH, 2014, 31 (05) : 1106 - 1119
  • [23] Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells
    Nanayakkara, Amila K.
    Follit, Courtney A.
    Chen, Gang
    Williams, Noelle S.
    Vogel, Pia D.
    Wise, John G.
    [J]. SCIENTIFIC REPORTS, 2018, 8
  • [24] Liposomes co-encapsulating doxorubicin and glucoevatromonoside derivative induce synergic cytotoxic response against breast cancer cell lines
    Novais, M. V. M.
    Gomes, E. R.
    Miranda, M. C.
    Silva, J. O.
    Gomes, D. A.
    Braga, F. C.
    Padua, R. M.
    Oliveira, M. C.
    [J]. BIOMEDICINE & PHARMACOTHERAPY, 2021, 136
  • [25] Liposomes: structure, composition, types, and clinical applications
    Nsairat, Hamdi
    Khater, Dima
    Sayed, Usama
    Odeh, Fadwa
    Al Bawab, Abeer
    Alshaer, Walhan
    [J]. HELIYON, 2022, 8 (05)
  • [26] Opsonins and Dysopsonins of Nanoparticles: Facts, Concepts, and Methodological Guidelines
    Papini, Emanuele
    Tavano, Regina
    Mancin, Fabrizio
    [J]. FRONTIERS IN IMMUNOLOGY, 2020, 11
  • [27] Co-delivery nanoparticles of anti-cancer drugs for improving chemotherapy efficacy
    Qi, Shan-Shan
    Sun, Jia-Hui
    Yu, Hao-Han
    Yu, Shu-Qin
    [J]. DRUG DELIVERY, 2017, 24 (01) : 1909 - 1926
  • [28] Ramon-Lopez A, 2012, Farm Hosp, V36, P392, DOI 10.1016/j.farma.2011.08.004
  • [29] Cisplatin for cancer therapy and overcoming chemoresistance
    Ranasinghe, Ranmali
    Mathai, Michael L.
    Zulli, Anthony
    [J]. HELIYON, 2022, 8 (09)
  • [30] Progress and challenges towards targeted delivery of cancer therapeutics
    Rosenblum, Daniel
    Joshi, Nitin
    Tao, Wei
    Karp, Jeffrey M.
    Peer, Dan
    [J]. NATURE COMMUNICATIONS, 2018, 9