Evaluation of lipid-stabilised tripropionin nanodroplets as a delivery route for combretastatin A4

[Display omitted] Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise for the delivery of different therapeutic agents. Although multiple studies have investigated the effects of the oil and pr...

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Published inInternational journal of pharmaceutics Vol. 526; no. 1-2; pp. 547 - 555
Main Authors Mico, Victoria, Charalambous, Antonia, Peyman, Sally A., Abou-Saleh, Radwa H., Markham, Alexander F., Coletta, P. Louise, Evans, Stephen D.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 30.06.2017
Subjects
Animals
Cells, Cultured
Combretastatin
Drug delivery
Endothelial Cells - drug effects
Mice
Nanoemulsion
Nanoparticles - chemistry
Oils - chemistry
Stilbenes - administration & dosage
Triglycerides - chemistry
Combretastatin
Drug delivery
Nanoemulsion
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Abstract [Display omitted] Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise for the delivery of different therapeutic agents. Although multiple studies have investigated the effects of the oil and preparation conditions on the size of the nanoemulsion nanodroplets for food applications, analogous studies for nanoemulsions for therapeutic applications are limited. Here we present a study on the production of lipid-stabilised oil nanodroplets (LONDs) towards medical applications. A number of biocompatible oils were used to form LONDs with phospholipid coatings, and among these, squalane and tripropionin were chosen as model oils for subsequent studies. LONDs were formed by high pressure homogenisation, and their size was found to decrease with increasing production pressure. When produced at 175MPa, all LONDs samples exhibited sizes between 100 and 300nm, with polydispersity index PI between 0.1 and 0.3. The LONDs were stable for over six weeks, at 4°C, and also under physiological conditions, showing modest changes in size (<10%). The hydrophobic drug combretastatin A4 (CA4) was encapsulated in tripropionin LONDs with an efficiency of approximately 76%, achieving drug concentration of approximately 1.3mg/ml. SVR mouse endothelial cells treated with CA4 tripropionin LONDs showed the microtubule disruption, characteristic of drug uptake for all tested doses, which suggests successful release of the CA4 from the LONDs.
AbstractList [Display omitted] Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise for the delivery of different therapeutic agents. Although multiple studies have investigated the effects of the oil and preparation conditions on the size of the nanoemulsion nanodroplets for food applications, analogous studies for nanoemulsions for therapeutic applications are limited. Here we present a study on the production of lipid-stabilised oil nanodroplets (LONDs) towards medical applications. A number of biocompatible oils were used to form LONDs with phospholipid coatings, and among these, squalane and tripropionin were chosen as model oils for subsequent studies. LONDs were formed by high pressure homogenisation, and their size was found to decrease with increasing production pressure. When produced at 175MPa, all LONDs samples exhibited sizes between 100 and 300nm, with polydispersity index PI between 0.1 and 0.3. The LONDs were stable for over six weeks, at 4°C, and also under physiological conditions, showing modest changes in size (<10%). The hydrophobic drug combretastatin A4 (CA4) was encapsulated in tripropionin LONDs with an efficiency of approximately 76%, achieving drug concentration of approximately 1.3mg/ml. SVR mouse endothelial cells treated with CA4 tripropionin LONDs showed the microtubule disruption, characteristic of drug uptake for all tested doses, which suggests successful release of the CA4 from the LONDs.
Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise for the delivery of different therapeutic agents. Although multiple studies have investigated the effects of the oil and preparation conditions on the size of the nanoemulsion nanodroplets for food applications, analogous studies for nanoemulsions for therapeutic applications are limited. Here we present a study on the production of lipid-stabilised oil nanodroplets (LONDs) towards medical applications. A number of biocompatible oils were used to form LONDs with phospholipid coatings, and among these, squalane and tripropionin were chosen as model oils for subsequent studies. LONDs were formed by high pressure homogenisation, and their size was found to decrease with increasing production pressure. When produced at 175MPa, all LONDs samples exhibited sizes between 100 and 300nm, with polydispersity index PI between 0.1 and 0.3. The LONDs were stable for over six weeks, at 4°C, and also under physiological conditions, showing modest changes in size (<10%). The hydrophobic drug combretastatin A4 (CA4) was encapsulated in tripropionin LONDs with an efficiency of approximately 76%, achieving drug concentration of approximately 1.3mg/ml. SVR mouse endothelial cells treated with CA4 tripropionin LONDs showed the microtubule disruption, characteristic of drug uptake for all tested doses, which suggests successful release of the CA4 from the LONDs.
Author Charalambous, Antonia
Evans, Stephen D.
Peyman, Sally A.
Abou-Saleh, Radwa H.
Coletta, P. Louise
Markham, Alexander F.
Mico, Victoria
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Keywords Combretastatin
Drug delivery
Nanoemulsion
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Snippet [Display omitted] Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare,...
Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise...
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elsevier
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Publisher
StartPage 547
SubjectTerms Animals
Cells, Cultured
Combretastatin
Drug delivery
Endothelial Cells - drug effects
Mice
Nanoemulsion
Nanoparticles - chemistry
Oils - chemistry
Stilbenes - administration & dosage
Triglycerides - chemistry
Title Evaluation of lipid-stabilised tripropionin nanodroplets as a delivery route for combretastatin A4
URI https://dx.doi.org/10.1016/j.ijpharm.2017.05.009
https://www.ncbi.nlm.nih.gov/pubmed/28495582
Volume 526
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