Hybrid Vesicle Stability under Sterilisation and Preservation Processes Used in the Manufacture of Medicinal Formulations

Polymers

LarsJ. C. Jeuken¹  PaulA. Beales²  Rashmi Seneviratne²  Michael Rappolt³ 

[1] School of Biomedical Sciences, Astbury Centre for Structural Molecular Biology and Bragg Centre for Materials Research, University of Leeds, LeedsLS2 9JT, UK;School of Chemistry, Astbury Centre for Structural Molecular Biology and Bragg Centre for Materials Research, University of Leeds, LeedsLS2 9JT, UK;School of Food Science and Nutrition and Bragg Centre for Materials Research, University of Leeds, LeedsLS2 9JT, UK;

关键词: liposomes;    polymersomes;    filtration;    freeze-thaw;    membrane mechanics;    encapsulation stability;   

DOI  :  10.3390/polym12040914

来源: DOAJ

【 摘 要 】

Sterilisation and preservation of vesicle formulations are important considerations for their viable manufacture for industry applications, particular those intended for medicinal use. Here, we undertake an initial investigation of the stability of hybrid lipid-block copolymer vesicles to common sterilisation and preservation processes, with particular interest in how the block copolymer component might tune vesicle stability. We investigate two sizes of polybutadiene-block-poly(ethylene oxide) polymers (PBd₁₂-PEO₁₁ and PBd₂₂-PEO₁₄) mixed with the phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) considering the encapsulation stability of a fluorescent cargo and the colloidal stability of vesicle size distributions. We find that autoclaving and lyophilisation cause complete loss of encapsulation stability under the conditions studied here. Filtering through 200 nm pores appears to be viable for sterilisation for all vesicle compositions with comparatively low release of encapsulated cargo, even for vesicle size distributions which extend beyond the 200 nm filter pore size. Freeze-thaw of vesicles also shows promise for the preservation of hybrid vesicles with high block copolymer content. We discuss the process stability of hybrid vesicles in terms of the complex mechanical interplay between bending resistance, stretching elasticity and lysis strain of these membranes and propose strategies for future work to further enhance the process stability of these vesicle formulations.

【 授权许可】

Unknown