Microfluidics based manufacture of liposomes simultaneously entrapping hydrophilic and lipophilic drugs

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Abstract

Despite the substantial body of research investigating the use of liposomes, niosomes and other bilayer vesicles for drug delivery, the translation of these systems into licensed products remains limited. Indeed, recent shortages in the supply of liposomal products demonstrate the need for new scalable production methods for liposomes. Therefore, the aim of our research has been to consider the application of microfluidics in the manufacture of liposomes containing either or both a water soluble and a lipid soluble drug to promote co-delivery of drugs. For the first time, we demonstrate the entrapment of a hydrophilic and a lipophilic drug (metformin and glipizide respectively) both individually, and in combination, using a scalable microfluidics manufacturing system. In terms of the operating parameters, the choice of solvents, lipid concentration and aqueous:solvent ratio all impact on liposome size with vesicle diameter ranging from ∼90 to 300 nm. In terms of drug loading, microfluidics production promoted high loading within ∼100 nm vesicles for both the water soluble drug (20–25% of initial amount added) and the bilayer embedded drug (40–42% of initial amount added) with co-loading of the drugs making no impact on entrapment efficacy. However, co-loading of glipizide and metformin within the same liposome formulation did impact on the drug release profiles; in both instances the presence of both drugs in the one formulation promoted faster (up to 2 fold) release compared to liposomes containing a single drug alone. Overall, these results demonstrate the application of microfluidics to prepare liposomal systems incorporating either or both an aqueous soluble drug and a bilayer loaded drug.

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Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume514
Issue number1
Early online date15 Nov 2016
DOIs
Publication statusPublished - 30 Nov 2016

Bibliographic note

© 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ Funding: EPSRC (EP/L015218/1 and EP/I033270/1) and EU H2020 (643381). Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.ijpharm.2016.09.027.

    Keywords

  • liposomes, microfluidics, water soluble drugs, poorly soluble drugs, bilayer loading, manufacturing

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