Scalable solvent-free production of liposomes

Abstract

Objectives A major challenge faced with the manufacture of liposomes is the high volumes of organic solvents used during manufacturing. Therefore, we have implemented an organic solvent‐free production method for drug‐loaded liposomes and demonstrated its applicability with both aqueous core‐loaded and bilayer‐loaded drugs. Methods Liposomes were produced by high shear mixing dry powder lipids with an aqueous buffer, followed by down‐sizing using a Microfluidizer processor. Liposomes were purified via tangential flow filtration and characterised in terms of size, polydispersity index, zeta potential and drug loading. Key findings Doxorubicin‐loaded PEGylated liposomes can be manufactured using this solvent‐free method with particle sizes of 100–110 nm, low polydispersity index (PDI) (<0.2) and high drug loading (97–98%). If required, liposomes can be further down‐sized via microfluidic processing without impacting drug loading. Similar results were achieved with non‐PEGylated liposomes. With bilayer‐loaded amphotericin B liposomes, again liposomes can be prepared within a clinically appropriate size range (100–110 nm in size, low PDI) with high drug loading (98–100%). Conclusions We apply a simple and scalable solvent‐free method for the production of both aqueous core or bilayer drug‐loaded liposomes.

RETRACTED: Liposomes: Structure, Biomedical Applications, and Stability Parameters With Emphasis on Cholesterol

“…Unlike most nanoparticles, which encounter serious challenges in entering the clinic for various reasons, including safety issues, liposomes are well accepted in the clinic, first liposome-based drug being approved was Doxil ® [( Anselmo and Mitragotri, 2015 ; Bulbake et al, 2017 ; Singh et al, 2020 )], a liposome-based Doxorubicin formulation that has been FDA approved in 1995 for the United States market to treat ovarian cancer and AIDS-related Kaposi’s sarcoma. Subsequently, various other liposomal-based drugs have been commercialized, such as DaunoXome ® , for the delivery of daunorubicin, approved in 1996 to manage advanced HIV-associated Kaposi’s sarcoma and several different formulations ( Khadke et al, 2020 ).…”

Facile Solvent-Free Preparation of Antioxidant Idebenone-Loaded Nanoparticles for Efficient Wound Healing

“…To overcome these shortcomings, in this study, we developed a solvent-free solubilization technique to obtain IB-loaded nanoparticles (IB@NPs) with high and stable antioxidant activity for efficient wound healing [ 28 , 29 ] ( Figure 1 ). If IB is dispersed in an aqueous solution using solubilization technology, its encapsulation efficiency, long-term stability, and bioavailability can be increased, which can be applied in various fields.…”

Quality by Design for enabling RNA platform production processes

“…Adopting generic LNP systems would thus be helpful with a view to better characterize the LNP formation process and transfer knowledge among RNA products against different disease targets. Finally, LNP purification should not be overlooked, as this step can significantly impact particle physical attributes and product thermostability [80,81].…”