Binding of Imipramine, Dosulepin, and Opipramol to Liposomes for Overdose Treatment

Howell, Brett A.; Chauhan, Anuj

doi:10.1002/jps.21683

Cited by 8 publications

(18 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…15 Modulation of liposomal internal pH may additionally serve to "trap" toxins once sequestered through effects on molecular ionization. 7 LIPs used in this study had been previously demonstrated as having the greatest affinity for imipramine (similar in structure to clomipramine) in previous work. 7 There was no internal pH modulation in the LIPs used in the present study, which may offer an avenue for further improvement in drug sequestering capacity.…”

Section: Discussionmentioning

confidence: 93%

“…4,5 Liposomes are spherical vesicles of phospholipids and effectively sequester amitriptyline and imipramine in vitro. 6,7 Specific advantages afforded by liposomes (LIPs) include increased surface area:volume ratios, the ability to modulate surface charge and internal pH, and the inherent lipid bilayer structure. To date, however, there are limited data on the antidotal efficacy of liposomal formulations in intact animal models.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Cave

Harvey

Shaw

et al. 2013

Academic Emergency Medicine

Self Cite

View full text Add to dashboard Cite

Objectives: Liposome (LIP)-like lipid dispersions have emerged as useful detoxification vehicles in vitro. The authors compare resuscitation with tailored LIPs, 20% intravenous lipid emulsion (ILE), and sodium bicarbonate (BIC), in a rabbit model of clomipramine toxicity.Methods: Sedated, instrumented New Zealand white rabbits underwent clomipramine infusion at 3.2 mg/kg/min to 50% baseline mean arterial pressure (MAP) and then at 1.6 mg/kg/min for 30 minutes. BIC (3 mL/kg 8.4%), ILE (3 mL/kg 20%), or LIP (24 mg/kg) were infused as rescue treatments at toxicity and were repeated at 10 minutes (n = 5 in each group). remains a difficult therapeutic challenge. Mainstays of therapy include aggressive supportive care and sodium bicarbonate (BIC)-initiated systemic alkalinization. 1 More recently, intravenous lipid emulsion (ILE) preparations have been forwarded as adjuncts to standard management of TCA toxicity with successful reports of use in animal models 2 and human subjects. 3 Both pharmacokinetic and pharmacodynamic mechanisms have been forwarded to explain the beneficial effects of ILE. The widely held lipid sink theory is that lipid sequesters certain xenobiotics (such as TCAs) and reduces toxicity by decreasing the free serum concentration of the offending toxin. 4,5 Liposomes are spherical vesicles of phospholipids and effectively sequester amitriptyline and imipramine in vitro. 6,7 Specific advantages afforded by liposomes (LIPs) include increased surface area:volume ratios, the ability to modulate surface charge and internal pH, and the inherent lipid bilayer structure. To date, however, there are limited data on the antidotal efficacy of liposomal formulations in intact animal models.We examined the effect of LIPs in an established animal model of TCA toxicity. Specifically, in this study we compare resuscitation with bicarbonate (BIC), ILE, and LIPs in a previously studied rabbit model of clomipramineinduced shock. METHODS Study DesignThis was a laboratory study of clomipramine-induced cardiotoxicity in a rabbit model. The study was approved by the institutional ethics committee of the

show abstract

Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Cave

Harvey

Shaw

et al. 2013

Academic Emergency Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, the concentration of albumin at 2.4% was low relative to blood concentration. There is however, work using plasma protein solutions suggesting liposomes are effective at sequestering toxin [5,6]. Adverse effects of liposomes -particularly haemolysis -were not measured in this protocol, but there is a considerable literature regarding the biocompatibility of pegylated liposomes [6].…”

Section: Discussionmentioning

confidence: 99%

“…This is the first demonstration of such an effect in a solution containing human red blood cells. The effect of liposomes in overdose has been previously modelled using physiologically based pharmacokinetic modelling [6]. This work suggests that liposomes at a concentration of 2gm/litre could have significant clinical effects in TCA overdose.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Liposomal binding of imipramine in human red cell/albumin solution with simulated plasmapharesis

Cave¹,

Raghavan²,

Burrows³

et al. 2013

J Pharm Technol Drug Res

Self Cite

View full text Add to dashboard Cite

There has been much recent interest in the use of intravenous lipid based products inthe treatment of tricyclic ntidepressant toxicity. High affinity liposomal carriers have been designed which may be more effective binders of tricyclic antidepressant than intravenous lipid emulsion in the setting of intoxication. The uniformity and size of the liposomes opens the theoretical potential for extracorporeal removal of drug once bound. Imipramine was added to a suspension of human red blood cells and albumin. Liposomes of known high affinity for tricyclics were then added to this suspension. It was hypothesized that the imipramine would be bound to liposomes, which could then be filtered off in a staged process, first using a commercially available plasmapharesis filter and then through a 100nm filter. tatistically significant reductions in imipramine concentration were seen in the final components post filtration, both red cell rich (median, 24% original level, IQR 9-43%) and "pharesate", liposomes filtered off (median 23%, IQR 9-37%). We have demonstrated significant experimental binding of imipramine to liposomes ina human albumin/red blood cell uspension, and have removed liposomes from thissuspension after drug sequestration. Further work is planned to investigate the effect ofliposomes in TCA toxicity in an animal model.

show abstract

Nanotherapeutics for Alleviating Anesthesia‐Associated Complications

Lu,

Wei,

Shi

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Current management of anesthesia‐associated complications falls short in terms of both efficacy and safety. Nanomaterials with versatile properties and unique nano‐bio interactions hold substantial promise as therapeutics for addressing these complications. This review conducts a thorough examination of the existing nanotherapeutics and highlights the strategies for developing prospective nanomedicines to mitigate anesthetics‐related toxicity. Initially, general, regional, and local anesthesia along with the commonly used anesthetics and related prevalent side effects are introduced. Furthermore, employing nanotechnology to prevent and alleviate the complications of anesthetics is systematically demonstrated from three aspects, that is, developing 1) safe nano‐formulization for anesthetics; 2) nano‐antidotes to sequester overdosed anesthetics and alter their pharmacokinetics; 3) nanomedicines with pharmacodynamic activities to treat anesthetics toxicity. Finally, the prospects and challenges facing the clinical translation of nanotherapeutics for anesthesia‐related complications are discussed. This work provides a comprehensive roadmap for developing effective nanotherapeutics to prevent and mitigate anesthesia‐associated toxicity, which can potentially revolutionize the management of anesthesia complications.

show abstract

Binding of Imipramine, Dosulepin, and Opipramol to Liposomes for Overdose Treatment

Cited by 8 publications

References 38 publications

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Liposomal binding of imipramine in human red cell/albumin solution with simulated plasmapharesis

Nanotherapeutics for Alleviating Anesthesia‐Associated Complications

Contact Info

Product

Resources

About