Journal article Open Access

Microfluidics based manufacture of liposomes simultaneously entrapping hydrophilic and lipophilic drugs

Sameer Joshi; Maryam T. Hussain; Carla B. Roces; Giulia Anderluzzi; Elisabeth Kastner; Stefano Salmaso; Daniel J. Kirby; Yvonne Perrie


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  <identifier identifierType="DOI">10.5281/zenodo.197095</identifier>
  <creators>
    <creator>
      <creatorName>Sameer Joshi</creatorName>
      <affiliation>Aston Pharmacy School, Life and Health Sciences, Aston University, Birmingham, UK. B4 7ET</affiliation>
    </creator>
    <creator>
      <creatorName>Maryam T. Hussain</creatorName>
      <affiliation>Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 7 Cathedral Street, Glasgow, UK. G4 0RE</affiliation>
    </creator>
    <creator>
      <creatorName>Carla B. Roces</creatorName>
      <affiliation>Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 7 Cathedral Street, Glasgow, UK. G4 0RE</affiliation>
    </creator>
    <creator>
      <creatorName>Giulia Anderluzzi</creatorName>
      <affiliation>Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via 9 Marzolo 5, 35131 Padova - Italy</affiliation>
    </creator>
    <creator>
      <creatorName>Elisabeth Kastner</creatorName>
      <affiliation>Aston Pharmacy School, Life and Health Sciences, Aston University, Birmingham, UK. B4 7ET</affiliation>
    </creator>
    <creator>
      <creatorName>Stefano Salmaso</creatorName>
      <affiliation>Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via 9 Marzolo 5, 35131 Padova - Italy</affiliation>
    </creator>
    <creator>
      <creatorName>Daniel J. Kirby</creatorName>
      <affiliation>Aston Pharmacy School, Life and Health Sciences, Aston University, Birmingham, UK. B4 7ET</affiliation>
    </creator>
    <creator>
      <creatorName>Yvonne Perrie</creatorName>
      <affiliation>Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 7 Cathedral Street, Glasgow, UK. G4 0RE</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Microfluidics based manufacture of liposomes simultaneously entrapping hydrophilic and lipophilic drugs</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2016</publicationYear>
  <subjects>
    <subject>liposomes</subject>
    <subject>microfluidics</subject>
    <subject>water soluble drugs</subject>
    <subject>poorly soluble drugs</subject>
    <subject>bilayer loading</subject>
    <subject>aqueous soluble drug</subject>
    <subject subjectScheme="url">http://id.loc.gov/authorities/subjects/sh88007108</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2016-11-15</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/197095</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsIdenticalTo">http://strathprints.strath.ac.uk/57040/</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsPreviousVersionOf">10.1016/j.ijpharm.2016.09.027</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/ecfunded</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://creativecommons.org/licenses/by-nc-nd/4.0/legalcode">Creative Commons Attribution Non Commercial No Derivatives 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;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.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100000780</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/643381/">643381</awardNumber>
      <awardTitle>TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development</awardTitle>
    </fundingReference>
  </fundingReferences>
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