Gadd, Adam J. R. published the artcileHigh potency of lipid conjugated TLR7 agonist requires nanoparticulate or liposomal formulation, COA of Formula: C13H7Cl2N5, the publication is European Journal of Pharmaceutical Sciences (2018), 268-276, database is CAplus and MEDLINE.
Here, we studied the effect of formulation on potency of a 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE) conjugated TLR7 agonist (DOPE-TLR7a) alongside assessing phys. form using Dynamic Light Scattering (DLS), Nanosight Particle Tracking (NTA) anal. and Small Angle X-ray Scattering (SAXS). A very high potency of DOPE-TLR7a conjugate (EC50 around 9 nM) was observed either when prepared by direct dilution from DMSO or when formulated into 400-700 nm large multilamella liposomes containing dimethyldioctadecylammonium bromide salt (DDA) and DOPE. When prepared by dissolution in DMSO followed by dilution in aqueous culture medium, 93 ± 5 nm nanoparticles were formed. Without dilution from solution in DMSO, no nanoparticles were observed and no immunostimulatory activity could be detected without this formulation step. SAXS anal. of the conjugate after DMSO dissolution/water dilution revealed a lamellar order with a layer spacing of 68.7 Å, which correlates with arrangement in groups of 3 bilayers. The addition of another immunostimulatory glycolipid, trehalose-6,6-dibehenate (TDB), to DOPE:DDA liposomes gave no further increase in immunostimulatory activity beyond that provided by incorporating DOPE-TLR7a. Given the importance of nanoparticle or liposomal formulation for activity, we conclude that the major mechanism for increased potency when TLR7 agonists are conjugated to macromols. is through alteration of phys. form.
European Journal of Pharmaceutical Sciences published new progress about 115204-76-7. 115204-76-7 belongs to nitriles-buliding-blocks, auxiliary class 5.6_Aromatics,Purines, name is 4-((2,6-Dichloro-9H-purin-9-yl)methyl)benzonitrile, and the molecular formula is C13H7Cl2N5, COA of Formula: C13H7Cl2N5.
Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts