SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study
Yi-Ping Fang,1,2 Chih-Hung Chuang,3 Yi-Jhun Wu,1 Hsin-Che Lin,1 Yun-Chi Lu4 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 2Department of Medical Research, Kaohsiung Medical University Hospital, 3Department of Medical Laboratory Science and Biotechnology, College of Health...
Guardado en:
| Autores principales: | , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/9cd75a128f0f4a81b14fd8182d6ba2c6 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:9cd75a128f0f4a81b14fd8182d6ba2c6 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:9cd75a128f0f4a81b14fd8182d6ba2c62021-12-02T02:21:27ZSN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study1178-2013https://doaj.org/article/9cd75a128f0f4a81b14fd8182d6ba2c62018-05-01T00:00:00Zhttps://www.dovepress.com/sn38-loaded-100-nm-targeted-liposomes-for-improving-poor-solubility--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yi-Ping Fang,1,2 Chih-Hung Chuang,3 Yi-Jhun Wu,1 Hsin-Che Lin,1 Yun-Chi Lu4 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 2Department of Medical Research, Kaohsiung Medical University Hospital, 3Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, 4Graduate Institute of Medicine, Collage of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Background: SN38 (7-ethyl-10-hydroxycamptothecin) is a camptothecin derivative acts against various tumors. However, SN38 is hydrolyzed in the physiological environment (pH 7.4), and this instability interferes with its potential therapeutic effect. Our objective was to investigate SN38-loaded liposomes to overcome the poor solubility of SN38 and its biodistribution, which further diminish its toxicity.Materials and methods: The sub-100 nm targeted liposomes was employed to deliver SN-38 and evaluate the characterization, release behaviors, cytotoxicity, in vivo pharmacokinetics and biochemical assay.Results: The SN38-loaded targeted liposomes consisted of small (100.49 nm) spherical nanoparticles with negative charge (-37.93 mV) and high entrapment efficiency (92.47%). The release behavior of the SN38-loaded targeted liposomes was fitted with Higuchi kinetics (R2=0.9860). Free SN38 presented initial burst release. The IC50 for the SN38-loaded targeted liposomes (0.11 µM) was significantly lower than for the SN38 solution (0.37 µM) in the MCF7 cell line (P<0.01). Confocal laser scanning microscopy also confirmed highly efficient accumulation in the MCF7 cells. Pharmacokinetics demonstrated that the SN38-loaded targeted liposomes had a slightly increased half-life and mean residence time and decreased area under the concentration–time curve and maximum concentration. The results suggested that retention was achieved while the exposure of SN38 was significantly decreased. A noninvasive in vivo imaging system also showed that the targeted liposomes selectively targeted MCF7 tumors. In vivo toxicity data demonstrated that the decrease in platelets was significantly improved by SN38-loaded targeted liposomes, and diarrhea was not observed in BALB/c mice.Conclusion: In summary, SN38-loaded targeted liposomes could be a good candidate for application in human breast cancer. Keywords: SN38, targeted liposome, pharmacokinetics, human breast cancer, toxicityFang YPChuang CHWu YJLin HCLu YCDove Medical PressarticleSN-38targeted liposomepharmacokineticshuman breast cancertoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2789-2802 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
SN-38 targeted liposome pharmacokinetics human breast cancer toxicity Medicine (General) R5-920 |
| spellingShingle |
SN-38 targeted liposome pharmacokinetics human breast cancer toxicity Medicine (General) R5-920 Fang YP Chuang CH Wu YJ Lin HC Lu YC SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study |
| description |
Yi-Ping Fang,1,2 Chih-Hung Chuang,3 Yi-Jhun Wu,1 Hsin-Che Lin,1 Yun-Chi Lu4 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 2Department of Medical Research, Kaohsiung Medical University Hospital, 3Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, 4Graduate Institute of Medicine, Collage of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Background: SN38 (7-ethyl-10-hydroxycamptothecin) is a camptothecin derivative acts against various tumors. However, SN38 is hydrolyzed in the physiological environment (pH 7.4), and this instability interferes with its potential therapeutic effect. Our objective was to investigate SN38-loaded liposomes to overcome the poor solubility of SN38 and its biodistribution, which further diminish its toxicity.Materials and methods: The sub-100 nm targeted liposomes was employed to deliver SN-38 and evaluate the characterization, release behaviors, cytotoxicity, in vivo pharmacokinetics and biochemical assay.Results: The SN38-loaded targeted liposomes consisted of small (100.49 nm) spherical nanoparticles with negative charge (-37.93 mV) and high entrapment efficiency (92.47%). The release behavior of the SN38-loaded targeted liposomes was fitted with Higuchi kinetics (R2=0.9860). Free SN38 presented initial burst release. The IC50 for the SN38-loaded targeted liposomes (0.11 µM) was significantly lower than for the SN38 solution (0.37 µM) in the MCF7 cell line (P<0.01). Confocal laser scanning microscopy also confirmed highly efficient accumulation in the MCF7 cells. Pharmacokinetics demonstrated that the SN38-loaded targeted liposomes had a slightly increased half-life and mean residence time and decreased area under the concentration–time curve and maximum concentration. The results suggested that retention was achieved while the exposure of SN38 was significantly decreased. A noninvasive in vivo imaging system also showed that the targeted liposomes selectively targeted MCF7 tumors. In vivo toxicity data demonstrated that the decrease in platelets was significantly improved by SN38-loaded targeted liposomes, and diarrhea was not observed in BALB/c mice.Conclusion: In summary, SN38-loaded targeted liposomes could be a good candidate for application in human breast cancer. Keywords: SN38, targeted liposome, pharmacokinetics, human breast cancer, toxicity |
| format |
article |
| author |
Fang YP Chuang CH Wu YJ Lin HC Lu YC |
| author_facet |
Fang YP Chuang CH Wu YJ Lin HC Lu YC |
| author_sort |
Fang YP |
| title |
SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study |
| title_short |
SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study |
| title_full |
SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study |
| title_fullStr |
SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study |
| title_full_unstemmed |
SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study |
| title_sort |
sn38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study |
| publisher |
Dove Medical Press |
| publishDate |
2018 |
| url |
https://doaj.org/article/9cd75a128f0f4a81b14fd8182d6ba2c6 |
| work_keys_str_mv |
AT fangyp sn38loadedlt100nmtargetedliposomesforimprovingpoorsolubilityandminimizingburstreleaseandtoxicityinvitroandinvivostudy AT chuangch sn38loadedlt100nmtargetedliposomesforimprovingpoorsolubilityandminimizingburstreleaseandtoxicityinvitroandinvivostudy AT wuyj sn38loadedlt100nmtargetedliposomesforimprovingpoorsolubilityandminimizingburstreleaseandtoxicityinvitroandinvivostudy AT linhc sn38loadedlt100nmtargetedliposomesforimprovingpoorsolubilityandminimizingburstreleaseandtoxicityinvitroandinvivostudy AT luyc sn38loadedlt100nmtargetedliposomesforimprovingpoorsolubilityandminimizingburstreleaseandtoxicityinvitroandinvivostudy |
| _version_ |
1718402544492871680 |