Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications

Abstract

In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming “the latest generation medicine” with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs.

Carbosilane Dendrimers Loaded with siRNA Targeting Nrf2 as a Tool to Overcome Cisplatin Chemoresistance in Bladder Cancer Cells

“…In 2018, the Food and Drug Administration and the European Medicines Agency approved the first-ever siRNA product loaded in a lipid-based nanoparticle for the treatment of a rare inherited condition, marking a significant milestone in the story of RNA interference (RNAi) [ 35 ]. On the other hand, dendrimers have already been approved for clinical application [ 36 ], and many clinical trials with dendrimers are now being conducted [ 37 , 38 ]. However, siRNA-loaded dendrimers to combat cancer disease are not yet approved for clinical purposes.…”

Gene Therapy in Cancer Treatment: Why Go Nano?

“…Al-Attar and collaborators evaluated a combination of drug delivery devices composed of holo-transferrin conjugated liposomes for siRNA (targeting BCR-ABL) delivery, and electrospun polycaprolactone-gelatin microfibers for resveratrol release [215]. For additional applications on liposomes for gene therapy see [50,209,[216][217][218][219].…”

Noncationic Material Design for Nucleic Acid Delivery

“…So far, we have summarized multiple noncationic materials design for nucleic acid delivery ( Table 3 ). Several of these materials (not limited to noncationic platforms) have been involved in preclinical and clinical trials, [ 124 ] including hyaluronic acids, [ 125 ] aptamers, [ 126 ] lipid‐based, [ 127 ] and GalNAc‐decorated nucleic acid therapeutics. [ 128 ] For noncationic carriers, the pursuit for clinical trials is still in its early stage, specifically regarding nucleic acid delivery.…”