Projects per year
Extensive research has been undertaken to investigate the effect of liposome size in vitro and in vivo. However, it is often difficult to generate liposomes in different size ranges that offer similar low polydispersity and lamellarity. Conventional methods used in the preparation of liposomes, such as lipid film hydration or reverse phase evaporation, generally give rise to liposomal suspensions displaying broad, multimodal size distribution combined with uncontrolled degree of lamellarity. In contrast, microfluidics allows highly homogeneous liposome dispersions to be produced and adjustment of microfluidic operating parameters (flow rate ratio (FRR) and total flow rate (TFR)) can offer size-tuning of liposomes (up to 300 nm, depending on the formulation). Herein, we demonstrate a novel method which allows the production of highly monodisperse, cationic liposomes over a wide particle size range (up to 750 nm in size). This is achieved through controlling the concentration of the aqueous buffer during production. Using this method, liposomes composed of 1,2-dioleoyl-sn-3-phosphoethanolamine (DOPE) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium (DDA) – DOPE:DOTAP and DOPE:DDA liposomes – of up to 750 nm were prepared and investigated. Investigating these formulations in vitro demonstrates that cellular uptake of small (40 nm) and large (>500 nm) liposomes in bone marrow-derived macrophages (BMDM) is similar terms of percentage of liposome+ cells and mean fluorescence intensity (MFI). However, significant differences are observed in BMDM uptake when represented in terms of number of liposomes, liposome surface area or liposome internal volume. In vivo biodistribution studies in mice show that by creating small (<50 nm) liposomes we can modify the clearance rates of these liposomes from the injection site and increase accumulation to the draining lymphatics.
|Number of pages||10|
|Journal||European Journal of Pharmaceutics and Biopharmaceutics|
|Early online date||22 Aug 2019|
|Publication status||Published - 31 Oct 2019|
- cationic liposomes
- liposome size
- macrophage uptake
- particle size
FingerprintDive into the research topics of 'A novel microfluidic-based approach to formulate size-tuneable large unilamellar cationic liposomes: formulation, cellular uptake and biodistribution investigations'. Together they form a unique fingerprint.
- 1 Finished
Data to support: A novel microfluidic-based approach to formulate size-tuneable large unilamellar cationic liposomes: formulation, cellular uptake and biodistribution investigations.
Perrie, Y. (Creator) & Lou Ramirez, G. (Creator), University of Strathclyde, 22 Mar 2019