Lipid formulation using multi-component condensation reaction and lipid nanoparticles made using the same

A compound according to Formula I

• wherein:
• L1 is —(CH2)n1—;
• L2 is —(CH2)n2—;
• each n1 and n2 independently is from 1, 2, 3, 4, 5, or 6;
• Q is selected from —(CRa2)—, —NH—[(CH2)aNH]b—, —NRb—, —(OCH2CH2)pO—, —P(═O)(CH3)—, —S—S—, or
• each Ra independently is H or C1-6alkyl;
• Rx is —C(═O)R2 or —CH2CH2C(═O)OCH2CH2S—S—(CH2)tCH3;
• Ry is
• or —CH2CH2C(═O)OCH2CH2S—S—(CH2)tCH3;
• a is from 2 to 5;
• b is from 1 to 3;
• r is from 1 to 4;
• s is from 0 to 3;
• p is from 1 to 5;
• each t independently is from 3 to 20;
• Rb is selected from H, C1-6alkyl, or
• L3 is —(CH2)n3—;
• n3 is from 1, 2, 3, 4, 5, or 6;
• each of R1, R2 and R7 if present, independently is selected from —C5-25alkyl, —C5-25alkenyl, —C5-25alkynyl, —(CH2)x—OC(═O)—(C5-25alkyl), —(CH2)x—C(═O)O—(C5-25alkyl), —(CH2)x—(CH2CH2O)y—(C1-12alkyl), —(CH2)x+2—S—S—(C1-12alkyl), or —(CH2)x+1—CH(OC1-12alkyl)2;
• each of R3, R4 and R8, if present, independently is selected from —C5-25alkyl, —C5-25alkenyl, —C5-25alkynyl, —(CH2)x—OC(═O)—(C5-25alkyl), —(CH2)x—C(═O)O—(C5-25alkyl), —(CH2)x—(CH2CH2O)y—(C1-12alkyl), —(CH2)x+2—S—S—(C1-12alkyl), or —(CH2)x+1—CH(OC1-12alkyl)2;
• each of R5, R6, and R9, if present, independently is selected from —C4-22alkyl, —(CH2)z+2N(C1-4alkyl)2, —(CH2)z+2(5- or 6-membered heterocyclyl optionally substituted with C1-4alkyl), —C1-6OPG, —(CH2)z+2(5- to 9-membered heteroaryl), or —(CH2)z+2N((CH2)z+1OPG)2, where PG is a silyl protecting group;
• x is from 0 to 10;
• y is from 1 to 5;
• and
• z is from 0 to 3.