Synthetic lipid-like materials for brain delivery

Patent metadata

Field	Value
Publication number	US-11666539-B2
Application number	US-202117339563-A
Country	US
Kind code	B2
Filing date	Jun 4, 2021
Priority date	May 4, 2020
Publication date	Jun 6, 2023
Grant date	Jun 6, 2023

Abstract

Disclosed are (i) compounds of formula I, or pharmaceutically acceptable salts thereof, and (ii) lipidoid nanoparticles comprising compound of formula I or pharmaceutically acceptable salts thereof, as well as their use as vehicles for drug delivery across the blood-brain barrier.

First claim

I claim:

1. A compound of formula I:
Y—W—R Lipid   (I),

or a pharmaceutically acceptable salt thereof, wherein
Y is

W is —NR 20 ;
R 20 is R Lipid ; and
each instance of R Lipid is independently of the structure:

wherein:
each instance of R 1 and R 2 is independently —H, —OH, —NHR 30 , or —SH;
R 3 and R 4 are both —H; or R 3 and R 4 are taken together to form an oxo (═O) group;
Z is —CH 2 —, —O—, —NR 30 —, or —S—;
X and Y 1 are independently —CH 2 —, —NR 30 —, —O—, —S—, or —Se—;
m is an integer selected from 1-3;
n is an integer selected from 1-14;
p is 0 or 1;
q is an integer selected from 1-10;
t is 0 or 1; and
R 30 is —H, C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl.

2. The compound of claim 1 , wherein, in at least one instance of R Lipid , R 1 and R 2 are —H, R 3 and R 4 are taken together to form an oxo (═O) group, and Z is O.

3. The compound of claim 1 , wherein, in at least one instance of R Lipid , m is 1.

4. The compound of claim 1 , wherein, in at least one instance of R Lipid , p is 1.

5. The compound of claim 1 , wherein, in at least one instance of R Lipid , q is an integer selected from 2-8.

6. The compound of claim 1 , wherein, in at least one instance of R Lipid , t is 0.

7. The compound of claim 1 , selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

8. A lipidoid composition, comprising a compound of claim 1 .

9. The lipidoid composition of claim 8 , further comprising a protein.

10. The lipidoid composition of claim 9 , wherein the protein is GFP-Cre.

11. The lipidoid composition of claim 8 , further comprising a nucleic acid.

12. The lipidoid composition of claim 11 , wherein the nucleic acid is Tau-ASO.

13. The lipidoid composition of claim 8 , further comprising a small molecule, wherein the small molecule is an antifungal agent or a chemotherapeutic agent.

14. The lipidoid composition of claim 13 , wherein the small molecule is selected from the group consisting of bortezomib, imatinib, gefitinib, erlotinib, afatinib, osimertinib, dacomitinib, daunorubicin hydrochloride, cytarabine, fluorouracil, irinotecan hydrochloride, vincristine sulfate, methotrexate, paclitaxel, vincristine sulfate, epirubicin, docetaxel, cyclophosphamide, carboplatin, lenalidomide, ibrutinib, abiraterone acetate, enzalutamide, pemetrexed, palbociclib, nilotinib, everolimus, ruxolitinib, epirubicin, pirirubicin, idarubicin, valrubicin, amrubicin, bleomycin, phleomycin, dactinomycin, mithramycin, streptozotecin, pentostatin, mitosanes, enediynes, glycosides, macrolide lactones, ixabepilone, pentostatin, salinosporamide A, vinblastine, vincristine, etoposide, teniposide, vinorelbine, docetaxel, camptothecin, hycamtin, pederin, theopederins, annamides, trabectedin, aplidine, and ecteinascidin 743 (ET743).

15. The lipidoid composition of claim 8 , wherein the lipidoid composition has a particle size of about 25 nm to about 1000 nm.

16. A pharmaceutical composition, comprising a lipidoid composition of claim 8 ; and a pharmaceutically acceptable carrier or excipient.

Assignees

• Tufts College

Inventors

• Xu Qiaobing

Classifications

• A61K38/45

  Transferases (2) · CPC title

• A61K9/5123 Primary

  Organic compounds, e.g. fats, sugars · CPC title

• A61K47/28

  Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid · CPC title

• A61K9/51 Primary

  Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)} · CPC title

• C07D209/16 Primary

  Tryptamines · CPC title