US2016008282A1PendingUtilityA1

Transdermal Drug Delivery Using Amphiphilic Dendron-Coil Micelles

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Assignee: TRUSTEES OF THE UNIVERSITYOF ILLINOIS BOARD OFPriority: Feb 22, 2013Filed: Feb 21, 2014Published: Jan 14, 2016
Est. expiryFeb 22, 2033(~6.6 yrs left)· nominal 20-yr term from priority
Inventors:Seungpyo HongYang Yang
C08G 83/004C08G 63/6852A61K 47/10A61K 31/138A61K 47/34C08G 63/664A61K 9/0014A61K 9/1075C08G 83/008
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Claims

Abstract

The invention generally relates to the field of drug delivery. In particular, the invention relates to amphiphilic dendron-coils, micelles thereof and their use for the transdermal delivery of drugs.

Claims

exact text as granted — not AI-modified
We claim: 
     
         1 . A method of transdermal delivery of a drug to a patient comprising administering to the patient a topical composition comprising a micelle and a pharmaceutically acceptable excipient,
 wherein the drug has a molecular weight over 500 g/mol, a 1-octanol/PBS partition coefficient (log P) less than 1 or greater than 3, or both, and   wherein the micelle comprises amphiphilic dendron-coils and encapsulates the drug, and   wherein each amphiphilic dendron-coil comprises a hydrophobic core-forming block, a polyester dendron and a poly(ethylene) glycol (PEG) moiety.   
     
     
         2 . The method of  claim 1  wherein the hydrophobic core-forming block comprises polycaprolactone (PCL), poly(lactic acid) (PLA), poly(glycolic acid) (PGA) or poly(lactic-co-glycolic acid) (PLGA); wherein the polyester dendron is a generation 3 to generation 5 polyester dendron with either an acetylene or carboxylate core; and wherein the PEG moiety is a methoxy PEG (mPEG) moiety, amine-terminated PEG (PEG-NH 2 ) moiety, acetylated PEG (PEG-Ac) moiety, carboxylated PEG (PEG-COOH) moiety, thiol-terminated PEG (PEG-SH) moiety, N-hydroxysuccinimide-actived PEG (PEG-NHS) moiety, NH 2 -PEG-NH 2  moiety or NH 2 -PEG-COOH moiety. 
     
     
         3 . The method of  claim 2  wherein the hydrophobic core-forming block comprises polycaprolactone (PCL), poly(lactic acid) (PLA), poly(glycolic acid) (PGA) or poly(lactic-co-glycolic acid) (PLGA). 
     
     
         4 . The method of  claim 2  wherein the hydrophobic core-forming block comprises PCL. 
     
     
         5 . The method of  claim 2  wherein the hydrophobic core-forming block comprises PLA. 
     
     
         6 . The method of  claim 2  wherein the hydrophobic core-forming block comprises PGA. 
     
     
         7 . The method of  claim 2  wherein the hydrophobic core-forming block comprises PLG. 
     
     
         8 . The method of  claim 3  wherein the PCL is poly(ε-caprolactone). 
     
     
         9 . The method of  claim 1 ,  2 ,  3 ,  4 ,  5 ,  6 ,  7  or  8  wherein the hydrophobic core-forming block has a molecular weight from about 0.5 kDa to about 20 kDa. 
     
     
         10 . The method of  claim 8  wherein the poly(ε-caprolactone) has a molecular weight of about 3.5 kDa. 
     
     
         11 . The method of  claim 8  wherein the poly(8-caprolactone) has a molecular weight of about 14 kDa. 
     
     
         12 . The method of  claim 1  wherein the polyester dendron has an acetylene core. 
     
     
         13 . The method of  claim 1  wherein the polyester dendron has a carboxylate core. 
     
     
         14 . The method of  claim 3  wherein the polyester dendron has an acetylene core. 
     
     
         15 . The method of  claim 3  wherein the polyester dendron has a carboxylate core. 
     
     
         16 . The method of  claim 4  or  8  wherein the polyester dendron has an acetylene core. 
     
     
         17 . The method of  claim 10  wherein the polyester dendron has an acetylene core. 
     
     
         18 . The method of  claim 11  wherein the polyester dendron has an acetylene core. 
     
     
         19 . The method of  claim 1 ,  12  or  13  wherein the polyester dendron is a generation 3 (G3) dendron. 
     
     
         20 . The method of  claim 1 ,  12  or  13  wherein the polyester dendron is a generation 4 (G4) dendron. 
     
     
         21 . The method of  claim 1 ,  12  or  13  wherein the polyester dendron is a generation 5 (G5) dendron. 
     
     
         22 . The method of  claim 12  wherein the polyester dendron is a generation 3 polyester-8-hydroxyl-1-acetylene bis-MPA dendron. 
     
     
         23 . The method of  claim 1  wherein the PEG moiety is a methoxy PEG (mPEG) moiety, amine-terminated PEG (PEG-NH 2 ) moiety, acetylated PEG (PEG-Ac) moiety, carboxylated PEG (PEG-COOH) moiety, thiol-terminated PEG (PEG-SH) moiety, N-hydroxysuccinimide-actived PEG (PEG-NHS) moiety, NH 2 -PEG-NH 2  moiety or NH 2 -PEG-COOH moiety. 
     
     
         24 . The method of any one of  claims 4 - 18 , or  22  wherein the PEG moiety is a methoxy PEG (mPEG) moiety, amine-terminated PEG (PEG-NH 2 ) moiety, acetylated PEG (PEG-Ac) moiety, carboxylated PEG (PEG-COOH) moiety, thiol-terminated PEG (PEG-SH) moiety, N-hydroxysuccinimide-actived PEG (PEG-NHS) moiety, NH 2 -PEG-NH 2  moiety or NH 2 -PEG-COOH moiety. 
     
     
         25 . The method of  claim 1  wherein the PEG moiety has a molecular weight from about 0.2 kDa to about 5 kDa. 
     
     
         26 . The method of  claim 24  wherein the PEG moiety has a molecular weight from about 0.2 kDa to about 5 kDa. 
     
     
         27 . The method of any one of the preceding claims wherein the micelle further comprises one or more ligands conjugated to one or more PEG moieties. 
     
     
         28 . The method of any one of the preceding claims wherein the micelle further comprises a chemical penetration enhancer. 
     
     
         29 . The method of any one of the preceding claims wherein the drug is hydrophobic. 
     
     
         30 . The method of any one of the preceding claims wherein the drug is an cancer drug. 
     
     
         31 . The method of  claim 30  wherein the cancer drug is paclitaxel, methotrexate, doxorubicin, cisplatin, carboplatin, tamoxifen, 4-hydroxytamoxifen, endoxifen, fulvestrant; canstatin, proliferin-related protein, restin, maspin, osteopontin, Secreted Protein Acidic and Rich in Cysteine (SPARC) protein, Vascular Endothelial cell Growth Inhibitor (VEGI), prolactin, prothrombin, Interferon (IFN)-alpha, IFN-beta, IFN-gamma, C-X-C motif chemokine 10 (CXCL10), Interleukin (IL)-4, IL-12, metalloprotease and Thrombospondin domains protein (METH)-1 and METH-2, Tissue Inhibitors of metalloproteinase (TIMP), cell division autoantigen 1 (CDA1), platelet factor-4, vasostatin, calreticulin, endostatin, angiostatin, thrombospondin (TSP)-1 and TSP-2, Angiopoietin 2, Vascular Endothelial Growth Factor Receptor (VEGFR)-1, or Novel SH2-containing Protein 1 (NSP-1). 
     
     
         32 . The method of any one of the preceding claims wherein the transdermal delivery of the drug is prolonged. 
     
     
         33 . The method of any one of the preceding claims wherein the transdermal delivery of the drug is biphasic.

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