The effect of ethanol evaporation on the properties of inkjet produced liposomes

Abstract

Background Inkjet method has been used to produce nano-sized liposomes with a uniform size distribution. However, following the production of liposomes by inkjet method, the solvent residue in the product could have a significant effect on the properties of the final liposomes. Objective This research paper aimed to find a suitable method to remove ethanol content and to study its effect on the properties of the final liposomal suspension. Method Egg phosphatidylcholine and lidocaine were dissolved in ethanol; and inkjet method at 80 kHz was applied to produce uniform droplets, which were deposited in an aqueous solution to form liposomes. Dry nitrogen gas flow, air-drying, and rotary evaporator were tested to remove the ethanol content. Liposome properties such as size, polydispersity index (PDI), and charge were screened before and after ethanol evaporation. Results Only rotary evaporator (at constant speed and room temperature for 2 h) removed all of the ethanol content, with a final drug entrapment efficiency (EE) of 29.44 ± 6.77%. This was higher than a conventional method. Furthermore, removing ethanol led to liposome size reduction from approximately 200 nm to less than 100 nm in most samples. Additionally, this increased the liposomal net charge, which contributed to maintain the uniform and narrow size distribution of liposomes. Conclusion Nano-sized liposomes were produced with a narrow PDI and higher EE compared to a conventional method by using an inkjet method. Moreover, rotary evaporator for 2 h reduced effectively the ethanol content, while maintaining the narrow size distribution.

A Comprehensive Review on Novel Liposomal Methodologies, Commercial Formulations, Clinical Trials and Patents

“…2 Schematic representation of Bangham method, adapted from [49] evaporate organic solvent from the prepared liposomes [51]. Hauschild et al developed the inkjet method as the modern method of ethanol injection; in this method the drug solution that is hydrophilic/lipophilic or both was dissolved in ethanol and transformed to inkjet device for the preparation of liposomes with tremendous control on particle size and for large-scale production [52]. Advantages…”

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“…Phospholipids will self-assemble into bilayers around the solution, forming liposomes. Liposomes produced with this method are 10–100 µm MLVs, not small enough for further applications, and as such it is usually combined with sonication or extrusion [ 21 ]. The DRV method includes the same first steps as the thin film hydration method; however, after the formation of liposomes, sonication or extrusion are applied to reduce the size of the vesicles.…”

“…The major drawbacks of this technique include its time-consuming process, a high organic residue in the final suspension, and difficulty removing ethanol since it forms an azeotropic mixture with water [ 24 ]. Furthermore, an evaporation could damage the structure of vesicles and the particle size distribution is difficult to control with this method [ 21 ]. Additionally, since lipids are poorly soluble in ethanol, ethanol injection often leads to the formation of heterogeneous liposomes [ 24 ].…”

Fabrication, characterization and optimization of nanostructured lipid carrier formulations using Beclomethasone dipropionate for pulmonary drug delivery via medical nebulizers

“…In the preceding decades, nano-carriers have gained popularity for the delivery of therapeutically active compounds into pulmonary system, in order to fulfil several requirements including; shielding drug degradation, drug loading ability, sustained release, biodegradation and biocompatibility; as well as formulation stability during nebulization using various nebulizers. Various lipid-based formulations fulfil these requirements and have successfully delivered APIs (active pharmaceutical ingredients) into the pulmonary system, these include: liposomes and proliposomes , Elhissi, 2017, Elhissi et al, 2011, Gala et al, 2015, Bnyan et al, 2020, transfersomes and protransfersomes (Bnyan et al, 2019, Khan et al, 2020a, Subramanian et al, 2016, Bnyan et al, 2018, niosomes and proniosomes (Najlah et al, 2015, Muzzalupo andMazzotta, 2019), ethosomes and nanoemulsions (Nasri et al, 2020, Pavoni et al, 2020, Nesamony et al, 2014, polymeric nanoparticles (Jarai et al, 2020, d'Angelo et al, 2015 and solid lipid nanoparticles (Liu et al, 2008, Esmaeili et al, 2016. Lipid nanoparticles are a popular research avenue for the delivery of hydrophobic drugs.…”