Rapid scale-up and production of active-loaded PEGylated liposomes

Carla B. Roces, Emily Charlotte Port, Nikolaos N. Daskalakis, Julie A. Watts, Jonathan Aylott, Gavin Halbert, Yvonne Perrie

Research output: Contribution to journalArticle

Abstract

Manufacturing of liposomal nanomedicines (e.g. Doxil®/Caelyx®) is a challenging and slow process based on multiple-vessel and batch processing techniques. As a result, the translation of these nanomedicines from bench to bedside has been limited. Microfluidic-based manufacturing offers the opportunity to address this issue, and de-risk the wider adoption of nanomedicines. Here we demonstrate the applicability of microfluidics for continuous manufacturing of PEGylated liposomes encapsulating ammonium sulfate (250 mM). Doxorubicin was subsequently active-loaded into these pre-formed liposomes. Critical process parameters and material considerations demonstrated to influence the liposomal product attributes included solvent selection and lipid concentration, flow rate ratio, and temperature and duration used for drug loading. However, the total flow rate did not affect the liposome product characteristics, allowing high production speeds to be adopted. The final liposomal product comprised of 80–100 nm vesicles (PDI < 0.2) encapsulating ≥ 90% doxorubicin, with matching release profiles to the innovator product and is stable for at least 6 months. Additionally, vincristine and acridine orange were active-loaded into these PEGylated liposomes (≥ 90% and ~100 nm in size) using the same process. These results demonstrate the ability to produce active-loaded PEGylated liposomes with high encapsulation efficiencies and particle sizes which support tumour targeting.

Original languageEnglish
Article number119566
Number of pages32
JournalInternational Journal of Pharmaceutics
Volume586
Early online date2 Jul 2020
DOIs
Publication statusPublished - 30 Aug 2020

Keywords

  • microfluidics
  • high-throughput
  • scalable
  • cost-effective
  • PEGylated liposomes
  • doxorubicin
  • vincristine
  • acridine orange

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Data for: "Rapid scale-up and production of active-loaded PEGylated liposomes"

Roces Rodriguez, C. B. (Creator), Perrie, Y. (Supervisor), Halbert, G. (Supervisor), Port, E. (Contributor) & Daskalakis, N. (Contributor), University of Strathclyde, 23 Jun 2020

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