Covid 19

Cancer vaccine (melanoma)

- Active compound, type of biologics 
Nucleic acids namely RNA interference RNAi siRNA (short interfering RNA) to reduce oncogenic Kras expression by binding to RNA molecules to block their expression.

- Formulation ingredients and their role
Exosomes with plasma membrane-like phospholipids , membrane-anchored proteins of exosomes may contribute to their diminished clearance from the circulation( CD47), - integrin functions in part to protect cells from phagocytosis, CD47 is the ligand for signal regulatory protein alpha (SIRPα), and CD47-SIRPα binding initiates the ‘don’t eat me’ signal that inhibits phagocytosis.

- Intracellular delivery strategy
exosome undergoes macropinocytosis by pancreatic tumor cells

protonated at low pH, which makes them positively charged, but they remain neutral at physiological pH (refs7,11,14). 

- The pH-sensitivity of ionizable lipids is beneficial for mRNA delivery in vivo, because neutral lipids have less interactions with the anionic membranes of blood cells and, thus, improve the biocompatibility of lipid nanoparticles 

- trapped in endosomes, in which the pH is lower than in the extracellular environment, ionizable lipids are protonated —> positively charged —> promote membrane destabilization and facilitate endosomal escape of the nanoparticles

ester bond in the linker and lipidic tail of lipid carrier: increase biodegradability —> better delivery efficacy and faster elimination from the liver and plasma in vivo 

- DSPC (phosphatidylcholine) with saturated tails, has a melting temperature of ~54 °C and a cylindrical geometry —>  DSPC molecules to form a lamellar phase —> stabilizes the structure of lipid nanoparticle

Bcl-2 siRNA: suppressed the expression of key apoptosis inhibitor Bcl-2

- Active compound, type of biologics
* MAPKAP kinase 2 inhibitory peptide (with different CPP-modification)
besides biologics, nanoparticles,  gene editing (CRSIPR/Cas9) are also explored.

- Site of action
* Intracellular

- Mechanism of action
* Prevent degradation of peptide drugs

- Formulation ingredients and their role
* PPAA: PPAA interacts with and coats the cell membrane through hydrophobic interactions --> decreases the negative charge of the cell membrane --> concentrate positively charged CPPs to the cell surface and induces cellular internalization

PPAA protonation in endosome (acidic environment) --> conformation change to a more hydrophobic and membrane-active form --> reduce interactions with cationic cargo

- Intracellular delivery strategy
macropinocytosis, clathrin-mediated entocytosis