This topic is lockedReading thru this fascinating study on mitochondria targeting pharma drugs.
https://www.ncbi.nlm...MC4350006/#B345
Diffusion through the IMM is difficult; therefore, mitochondria-targeted compounds need to be encapsulated inside a drug carrier. Moreover, this encapsulation and the subsequent release of the compound inside the mitochondrion must preserve the drug's pharmacological stability/activity. In recent years, great efforts have been made to find solutions for the development of efficient drug carriers. These molecules display several features: (i) ability for binding to the pharmacologically active form of the drug or a prodrug; (ii) an efficient transport system that carries the drug to the site of its action; (iii) specific and selective targeting to the mitochondrial compartment; and (iv) release of the drug inside the mitochondrion (Fig. 7). Current strategies for mitochondrial drug delivery include passive and active targeting (287). In the case of active targeting, specific interactions that take place at mitochondrial sites, including ligand-receptor associations and antigen-antibody binding, are exploited and take advantage of the compatibility between the physicochemical properties of the carrier molecule (electric charge, hydrophilicity, size, and mass) and those of the mitochondrial compartment. Due to mitochondrial morphological properties, passive targeting to these organelles is difficult; hence, active targeting strategies are being developed.
Its a method of delivering the drug direct to the mitochondria instead of just gulping it down and hope it finds its way there. Apparently just making a liposome using small molecules will help to increase the drug's mito penetration.
Small molecules have been efficiently targeted to mitochondria in vivo by several targeting strategies; namely, through enclosure inside liposomes (287), conjugation to lipophilic cations (210), and incorporation into mitochondria-targeted peptides (315) (Table 1). So far, the molecules employed in these approaches involve relevant antioxidants as well as substrates and coenzyme components of the ETC, such as cytochrome c, B2, succinate, and vitamin B1, and proapoptotic proteins including those of the Bax/Bcl2 family and p53 (287).
Whats interesting to me about this passage is that of all the nutrients/drugs they thought to put into a mito targetting pharma, NAD+ somehow didn't make the list. I mean isn't this a no brainer? Am I missing something here?
Imagine taking a small molecule liposomal drug that delivers NAD+ direct to your mitochondria. Not NR, not NMN, but actual NAD+.
Now theoretically there is a way you can make liposomes at home using lecithing and a ultrasonic jewerly cleaner, however if this method actually makes real honest to gosh liposomes is unproven AFAIK. Although if anyone has other info please post. But if that method does, in fact, work, you could get pure NAD powder and make liposomal NAD+.
Of course that DIY method doesn't involve small molecules. And honestly would your homemade liposomes even survive the stomach acid journey? Unknown. Still something to think about
