期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 586, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2020.119566
关键词
Microfluidics; High-throughput; Scalable; Cost-effective; PEGylated liposomes; Doxorubicin; Vincristine; Acridine orange
资金
- Centre for Process Innovation (CPI) within the National Formulation Centre (NFC)
- Engineering and Physical Sciences Research Council (EPSRC) [EP/L022494/1]
- University of Nottingham
- EPSRC [EP/P006965/1, EP/P006485/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/P006485/1, EP/N009126/1] Funding Source: researchfish
Manufacturing of liposomal nanomedicines (e.g. Doxil (R)/Caelyx (R)) 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 similar to 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.
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