Chemical Engg. Seminar Series : Dr. Nikhil Subraveti

Lipid nanoparticles and hydrogels for drug and gene delivery

Abstract: The field of drug and gene delivery has traditionally relied on nano- or micro-particles like liposomes and hydrogels. A new platform that has recently emerged has been lipid nanoparticles (LNPs), which form the basis for vaccines used against COVID-19. With all these platforms, there is a need to enhance the functionality of the particles. Critical challenges include: (1) achieving targeted delivery with high specificity; (2) efficiently encapsulating complex cargo, such as nucleic acids for gene editing; and (3) precisely controlling the kinetics of cargo release to minimize dosing frequency.

In this talk, I will discuss how chemical engineers can contribute to both the design of novel particles as well as their large-scale manufacture. With regard to LNPs, while microfluidics is commonly used for small-scale LNP production, its limitations—such as high costs and fouling—hinder its scale-up potential. I will demonstrate the use of confined impinging jet (CIJ) mixers for the scalable production of LNPs. Additionally, I will present next-generation LNPs using block copolymer stabilizers, as well as antibody-conjugated LNPs. These new LNPs show improved ability to target non-hepatic cells, including model T-cells. 

Finally, I will introduce a platform of hydrogel containers covered with “smart” polymeric skins. These containers can slowly release small molecules for days and can even achieve the elusive “holy grail” of zero-order release (i.e., release at a constant rate) for an extended period. Moreover, I will show that release of small molecules can be switched ON and OFF in a cyclic manner by engineering the redox chemistry of the skin.