APR September/October 2020 - 118

VENDOR VIEWPOINT

Harnessing Synthetic Lipids
for Drug Development:
Strategies for Success
Shiksha Mantri
MilliporeSigma

Lipids are gaining enhanced momentum due to their vital role in the field of ribonucleic acid
(RNA) therapeutics and vaccine development for diseases such as cancer and COVID-19.
Currently, there are 18 liposomal drugs approved by the U.S. Food and Drug Administration
(FDA) and hundreds of lipid-based drug candidates in the clinic for a range of ailments. Lipidbased formulations and lipid nanoparticles have shown promise in drug development and
delivery due to their ability to:
*

Enhance active pharmaceutical ingredient (API) stability by protecting the API from
immune response, proteases and other factors (Yingchoncharoen, 2016)

*

Boost the solubility and bioavailability of drugs with poor water solubility
(Yingchoncharoen, 2016)

*

Passively target inflamed or tumor tissues due to their leaky vasculature
(Danhier, 2010)

*

Improve the toxicity profile of the entrapped API; targeted drug delivery could
improve the toxicity profile of the API further as the APIs are delivered directly to the
site of action (Yingchoncharoen, 2016)

*

Ability to deliver difficult APIs such as RNA, which are prone to instability, nucleasemediated lysis, strong immune responses, and inability to reach the site of action.

The newest advancements in lipid-based drug delivery research and drug development is in
the field of nucleic acid delivery, for APIs such as short RNAs for gene silencing or activation (for
e.g. siRNA, miRNA, saRNA) and long RNA (mRNA) for applications in cancer therapy, enzyme
replacement therapy, vaccines, and more. The first vaccine to enter clinical trials for COVID-19
was a mRNA vaccine, where the mRNA of a viral antigen was encapsulated in a lipid nanoparticle.

Methods of Liposome Manufacturing
Shiksha Mantri is the Global
Technical Product Manager
for synthetic lipids and
responsible for the entire
GMP lipids business (portfolio and custom
manufacturing) at MilliporeSigma. In her
current role, she supports the top industry
players and young start-ups in the RNA
delivery and vaccines fields. She holds a
PhD in Chemical Biology from the University
of Oxford, U.K. and did her postdoc at ETH
Zurich, Switzerland.

There are numerous methods for liposome manufacturing (Wagner and Vorauer-Uhl, 2011).
The challenge for liposome drug producers lies in ensuring liposome manufacturing in a
scalable, robust and efficient process.
The rehydration manufacturing process involves the dissolution of lipid molecules in a solvent,
a drying step and a hydration step under agitation followed by energy input such as sonification
or extrusion to downsize the vesicles to unilamellar vesicles of a homogeneous distribution,
followed by purification. Depending on whether the API is hydrophobic or hydrophilic, the API
is added either with the organic solvent during the initial dissolution of the lipid or with the
aqueous solution during the hydration step.
Another manufacturing method of note is the solvent injection method, where the lipids are
dissolved in a solvent-like ethanol and rapidly mixed with an aqueous medium containing the
API as shown in Figure 1.
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