Background: The molecular mechanism of silencing genes using small interference
RNA is as particular and innovative phenomenon as the proposed delivery systems to release them.
Recent advances in RNAi have resulted in the development of multiple siRNA candidates that
are currently being evaluated in preclinical / clinical instances. SNALP®, Atuplex® and Rondel®
technologies stand out; they are mainly based on polymers, cyclodextrins or lipids.
Method: The objective of this work is to review the main features that Gene Therapy Medicinal
Product under current clinical evaluation present from a pharmaceutical technology point of view; it
tries to bring up theoretical concepts that give scientific support to the interpretation of data obtained
during pharmaceutical development process. It is basically focused on improving the translation
from bench/theoretical concepts to bedside of non viral vectors carrying siRNA.
Results: The extensive presence of lipid-based nanoparticle non-viral systems in clinical stages is
due to the advantages of their formulations. These include: safety, low immunogenicity, high
degree of material properties control, function tuning and ability to impact pharmacokinetics and
in vivo biodistribution. This work presents a pharmaceutical approach so as to improve the potential
of success in siRNA delivery using liposomal systems.
Conclusion: Formulation design should be increasingly addressed with industrial criteria; it should be
based on quality by design and on the estimation of critical attributes that affect product performance,
and supported by a range of characterization techniques and appropriate analytical methods.