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LIU Yanjiao, WEN Cheng, LI Dan, GAO Pei, ZHU Guodong. Secretory phospholipase A2 responsiveness and in vitro anti-tumor activity of oxaliplatin-loaded liposomes modified with facial amphiphiles[J]. Journal of China Pharmaceutical University, 2022, 53(4): 441-451. DOI: 10.11665/j.issn.1000-5048.20220407
Citation: LIU Yanjiao, WEN Cheng, LI Dan, GAO Pei, ZHU Guodong. Secretory phospholipase A2 responsiveness and in vitro anti-tumor activity of oxaliplatin-loaded liposomes modified with facial amphiphiles[J]. Journal of China Pharmaceutical University, 2022, 53(4): 441-451. DOI: 10.11665/j.issn.1000-5048.20220407
shu

Secretory phospholipase A2 responsiveness and in vitro anti-tumor activity of oxaliplatin-loaded liposomes modified with facial amphiphiles

  • School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529030, China

Funds: This study was supported by the National Natural Science Foundation of China (No.8167131086)
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  • Received Date: February 24, 2022
  • Revised Date: June 01, 2022
    Graphical Abstract
    • Abstract
  • Modulating drug release from liposomes at tumor sites are important for eliciting therapeutic effects of platinum drugs considering their low permeability through liposomal membranes, here a novel secretory phospholipase A2 (sPLA2) responsive-liposome system was constructed for oxaliplatin (L-OHP).Lipid ingredients dipalmitoyl phosphatidylcholine and distearoyl phosphoethanolamine-PEG2k, together with facial amphiphiles (FAs) including lithocholic acid (LCA) or 3-keto lithocholic acid (kLCA) were used to prepare sPLA2 responsive-liposome (LCA-Lip or kLCA-Lip) by thin-film hydration method.The physicochemical properties, sPLA2-responsive drug release and anti-tumor activity were evaluated in vitro.The results indicated L-OHP loaded liposomes modified with FAs had similar particle sizes of approximately 100 nm and narrow size distributions (PDI < 0.11).Compared with non-FAs-containing liposomes (C-Lip), LCA-Lip or kLCA-Lip has a comparable entrapment efficiency and loading efficiency.LCA-Lip or kLCA-Lip didn't show significant higher drug leakage at the presence of 10% or 50% fetal bovine serum (FBS) in media than that in media without FBS.Treated with secretory phospholipase A2 from Colo205 cells culture conditioned medium (CCM sPLA2) for 24 h, FAs modified liposomes released about 70% of carboxyfluorescein (CF), while C-Lip only released 20% of CF.Compared to L-OHP loaded C-Lip, L-OHP-loaded FAs-included formulations had much greater anti-proliferative activity against sPLA2-secreting Colo205 cells.In summary, our results shows that LCA or kLCA promotes responsiveness of liposomes to tumor-related sPLA2 and points to a new way to develop platium drugs-loaded liposomal delivery systems with better release mechanisms.
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    • References (36)
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