PEGylation of lipophilic SN38 prodrug with DSPE-mPEG2000 versus cremophor EL: comparative study for intravenous chemotherapy

Autor: Chunhan Luo, Xing Duan, Fuyue Liu, Anqin Li, Jun Zeng, Yifang Gan, Yaxin Zheng, Chen Li, Li Jia, Lu Yan
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Drug
Glycerol
Male
media_common.quotation_subject
Pharmaceutical Science
02 engineering and technology
Pharmacology
Irinotecan
030226 pharmacology & pharmacy
Polyethylene Glycols
Rats
Sprague-Dawley
03 medical and health sciences
Mice
0302 clinical medicine
Drug Delivery Systems
Cell Line
Tumor
PEG ratio
Cremophor EL
Animals
Prodrugs
Particle Size
Cytotoxicity
media_common
Drug Carriers
Mice
Inbred BALB C
Chemistry
Phosphatidylethanolamines
lcsh:RM1-950
PEGylation
General Medicine
Prodrug
021001 nanoscience & nanotechnology
lipophilic prodrug
nanomedicine
Xenograft Model Antitumor Assays
Rats
SN38
lcsh:Therapeutics. Pharmacology
Toxicity
Drug delivery
Nanomedicine
Nanoparticles
Topoisomerase I Inhibitors
0210 nano-technology
Colorectal Neoplasms
Hydrophobic and Hydrophilic Interactions
Research Article
Zdroj: Drug Delivery
Drug Delivery, Vol 26, Iss 1, Pp 354-362 (2019)
ISSN: 1521-0464
1071-7544
Popis: The lipophilic prodrug of hydrophobic drugs with well-designed molecular structures can form stable pure prodrug nanoparticles (NPs), but rapid NPs aggregation in plasma greatly restricted their direct use for intravenous chemotherapy. To address this, DSPE-mPEG2000 and Cremophor EL are two of the most widely used lipophilic PEG derivatives to enhance their colloidal stability in plasma. However, their drug delivery performances have never been comparatively studied. Here, a redox-responsive lipophilic prodrug of SN38 was chosen as the model drug for such comparative investigations. We found that Cremophor EL/NPs having a small diameter (∼15 nm) and poor kinetic stability displayed an enhanced cell internalization, higher cytotoxicity and prolonged circulation time as compared with DSPE-mPEG2000/NPs. Most importantly, these superiorities further resulted in a much more potent antitumor activity in CT26 colorectal cancer xenograft, but the increased loss of body weight was also noted. These results suggested that Cremophor EL could be more advantageous than DSPE-mPEG2000 in terms of the improvement of antitumor activity, but the enhanced toxicity warranted further attention in the future study.
Databáze: OpenAIRE
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