Bolaamphiphilic compounds, compositions and uses thereof
Bolaamphiphilic compounds are provided according to formula I: HG 2 -L 1 -HG 1 I where HG 1 , HG 2 and L 1 are as defined herein. Provided bolaamphiphilic compounds and the pharmaceutical compositions thereof are useful for delivering HIV active drugs into animal or human brain.
1. A formulation containing vesicles comprising one or more bolaamphiphilic compounds, cholesteryl hemisuccinate, cholesterol, stearyl amine, and an active agent which is tenofovir or fosamprenavir ({[(2R,3S)-1-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxy}phosphonic acid), wherein the pH has been adjusted to a pH of 7.5 or 8 using a buffer to maximize tenofovir encapsulation
wherein for 1 mL of formulation the components are: 10 mg GLH 19 and GLH 20 in a ratio of 2/1, 1 mg GLH-55b, 2.4 mg cholesteryl hemisuccinate, 1.6 mg cholesterol, 2.5 mg stearyl amine, and 5 mg tenofovir or fosamprenavir ({[(2R,3S)-1-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxy}phosphonic acid);
and the buffer is a HEPES, wherein
GLH 19 is
wherein
HG is
each p1 and p2 is an integer from 1-400, and R 7a is H or an acyl group.
2. A formulation of claim 1 suitable for IV, IP, oral, or transdermal administration for delivery of the active agent above its therapeutic threshold of 100 ng/mL.
3. A formulation of claim 1 suitable for IV, IP, oral, or transdermal administration for delivery of the active agent above its therapeutic threshold of 100 ng/100 mL.
4. A formulation of claim 1 wherein for 1 mL of formulation the components are: 10 mg GLH 19 and GLH 20 in a ratio of 2/1, 1 mg GLH-55b, 2.4 mg cholesteryl hemisuccinate, 1.6 mg cholesterol, 2.5 mg stearyl amine, and 5 mg tenofovir; and the buffer is a HEPES buffer.
5. A formulation of claim 1 , wherein the pH has been adjusted to a pH of 7.5.