ABSTRACT
The remarkable success of two lipid nanoparticle-mRNA vaccines against coronavirus disease (COVID-19) has placed the therapeutic and prophylactic potential of messenger RNA (mRNA) in the spotlight. It has also drawn attention to the indispensable role of lipid nanoparticles in enabling the effects of this nucleic acid. To date, lipid nanoparticles are the most clinically advanced non-viral platforms for mRNA delivery. This is thanks to their favorable safety profile and efficiency in protecting the nucleic acid from degradation and allowing its cellular uptake and cytoplasmic release upon endosomal escape. Moreover, the development of lipid nanoparticle-mRNA therapeutics was already a very active area of research even before the COVID-19 pandemic, which has likely only begun to bear its fruits. In this Review, we first discuss key aspects of the development of lipid nanoparticles as mRNA carriers. We then highlight promising preclinical and clinical studies involving lipid nanoparticle-mRNA formulations against infectious diseases and cancer, and to enable protein replacement or supplementation and genome editing. Finally, we elaborate on the challenges in advancing lipid nanoparticle-mRNA technology to widespread therapeutic use.
Subject(s)
COVID-19 , Liposomes , Nanoparticles , Humans , COVID-19/therapy , COVID-19 Vaccines , Pandemics , Endosomes , RNA, Messenger/genetics , Nanoparticles/therapeutic useABSTRACT
Obesity has grown to epidemic proportions with 2.1 billion people being overweight worldwide. A food-grade expandable capsule named EndoXpand for the treatment of overweight people was designed and developed in this study. EndoXpand consists of an inner expandable material (core), an embracing membrane, and a gelatin capsule shell. It is designed to occupy volume in the stomach and reduce hunger sensation. The occupied volume is changeable over time, dependent on the number of ingested capsules and their degradation time. This will avoid gastric accommodation to constant volume devices as seen in the use of intragastric balloons. Several materials were tested. Collagen casing was selected as the membrane and corn silk was used to tie the membrane. Dried black fungus (Auricularia auricula) was the biological material that expanded most. However, synthesized cellulose-based hydrogel expanded more and was chosen as the optimal expandable core material. The hydrogel-based EndoXpand expanded 72 times after soaking in an acidic environment for 80 min. The corn silk ligations weakened and broke after 3 h. This resulted in release of the expanded material that was designed to easily pass the pylorus and travel down the intestine for digestion or excretion. In conclusion, this study provides design and in vitro proof-of-technology data for a potential groundbreaking approach. Further studies are needed in animal models and human phase I studies.
