Secretory phospholipase A<sub>2</sub> responsiveness and <i>in vitro</i> anti-tumor activity of oxaliplatin-loaded liposomes modified with facial amphiphiles

LIU Yanjiao; WEN Cheng; LI Dan; GAO Pei; ZHU Guodong

doi:10.11665/j.issn.1000-5048.20220407

Journal of China Pharmaceutical University > 2022 > 53(4): 441-451. > DOI: 10.11665/j.issn.1000-5048.20220407

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

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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

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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 sPLA₂responsive-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.
- secretory phospholipase A₂,
- triggered-release,
- lithocholic acid,
- 3-keto lithocholic acid,
- enzyme-responsive liposome,
- anti-tumor activity,
- facial amphiphiles

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

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