edoc

Rapid optimization of liposome characteristics using a combined microfluidics and design-of-experiment approach

Sedighi, Mahsa and Sieber, Sandro and Rahimi, Fereshteh and Shahbazi, Mohammad-Ali and Rezayan, Ali Hossein and Huwyler, Jörg and Witzigmann, Dominik. (2019) Rapid optimization of liposome characteristics using a combined microfluidics and design-of-experiment approach. Drug delivery and translational research, 9 (1). pp. 404-413.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/65760/

Downloads: Statistics Overview

Abstract

Liposomes have attracted much attention as the first nanoformulations entering the clinic. The optimization of physicochemical properties of liposomes during nanomedicine development however is time-consuming and challenging despite great advances in formulation development. Here, we present a systematic approach for the rapid size optimization of liposomes. The combination of microfluidics with a design-of-experiment (DoE) approach offers a strategy to rapidly screen and optimize various liposome formulations, i.e., up to 30 liposome formulations in 1 day. Five representative liposome formulations based on clinically approved lipid compositions were formulated using systematic variations in microfluidics flow rate settings, i.e., flow rate ratio (FRR) and total flow rate (TFR). Interestingly, flow rate-dependent DoE models for the prediction of liposome characteristics could be grouped according to lipid-phase transition temperature and surface characteristics. For all formulations, the FRR had a significant impact (p < 0.001) on hydrodynamic diameter and size distribution of liposomes, while the TFR mainly affected the production rate. Liposome characteristics remained constant for TFRs above 8 mL/min. The stability study revealed an influence of lipid:cholesterol ratio (1:1 and 2:1 ratio) and presence of PEG on liposome characteristics during storage. To validate our DoE models, we formulated liposomes incorporating hydrophobic dodecanethiol-coated gold nanoparticles. This proof-of-concept step showed that flow rate settings predicted by DoE models successfully determined the size of resulting empty liposomes (109.3 ± 15.3 nm) or nanocomposites (111 ± 17.3 nm). This study indicates that a microfluidics-based formulation approach combined with DoE is suitable for the routine development of monodisperse and size-specific liposomes in a reproducible and rapid manner.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Sieber, Sandro and Witzigmann, Dominik
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer
ISSN:2190-393X
e-ISSN:2190-3948
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:11 Sep 2020 12:10
Deposited On:11 Sep 2020 12:10

Repository Staff Only: item control page