Intravenous DOPG liposomes do not augment pH gradient liposome supported peritoneal dialysis in treatment of acute intravenous amitriptyline intoxication in rats

Abstract

Introduction: Liposomes are nanospheres of lipid bilayer which can bind drug either in the phospholipid membrane or in the central aqueous droplet. Liposomes loaded with a drug can facilitate drug delivery, and empty liposomes can sequester certain drugs to reduce aqueous drug concentrations in experimental intoxication. Therapeutic dialysis in intoxication is limited by drug volumes of distribution and blood protein binding. In rats intoxicated with intravenous amitriptyline, we examined adding intravenous membrane-binding 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG) liposomes to liposome supported peritoneal dialysis (LSPD) in which liposomes in dialysate were augmented with an acidic core. The hypothesis was that a “gradient of liposome affinity” would increase LSPD amitriptyline concentrations.

Methods: Seven control and five intravenous DOPG liposome pre-treated rats were injected with amitriptyline, followed 10 min later by a 10-min LSPD dwell.

Results: DOPG liposomes increased blood amitriptyline concentrations by 50%; control (median [IQR] 1250 [951–1356] nmol/L; intravenous DOPG 1702 [1602–1864] nmol/L, p = 0.032). However, there was no corresponding increase in LSPD dialysate amitriptyline concentrations at the end of the dwell; control (median [IQR] 430 [334–2180] nmol/l, intravenous DOPG 414 [387–483] nmol/L p = 0.75).

Conclusions: Pre-treatment with DOPG liposomes decreased amitriptyline volume of distribution but had no significant effect on elimination of amitriptyline by LSPD.

Keywords:

• Amitriptyline
• poisoning
• dialysis
• peritoneal dialysis
• liposomes

Acknowledgements

The authors would like to acknowledge Mr. Ric Broadhurst and Mr. Robert Smith of Agresearch Ruakura for assistance with the experiment. We also wish to acknowledge Miss Emma Kang for assistance with liposome manufacture.

Disclosure statement

The authors declare no conflicts of interest.

Funding

This study was self-funded by the authors.

Data availability

Granular data from this experiment are available on reasonable request