Designing dendrimers for ocular drug delivery.
New series of phosphorus-containing dendrimers, having one quaternary ammonium salt as core and carboxylic acid terminal groups have been synthesized from generation 0 (3 carboxylic acid terminal groups) to generation 2 (12 carboxylic acid terminal groups). These dendrimers react with the neutral form of carteolol (an ocular anti-hypertensive drug used to treat glaucoma) to afford ion pair (saline) species. The solubility in water of these charged dendrimers depends on the generation considered: generation 0 (3 carteolol) is well soluble, whereas generation 1 (6 carteolol) and generation 2 (12 carteolol) are poorly soluble. These dendrimers have been tested in vivo, as vehicle for ocular drug delivery of carteolol to rabbits.
Spataro
Grégory
G
CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, F-31077 Toulouse, France.
Malecaze
François
F
Turrin
Cédric-Olivier
CO
Soler
Vincent
V
Duhayon
Carine
C
Elena
Pierre-Paul
PP
Majoral
Jean-Pierre
JP
Caminade
Anne-Marie
AM
D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry; D002354:Carteolol / Q000737:chemistry / Q000627:therapeutic use; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D004334:Drug Administration Schedule; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D015195:Drug Design; D005123:Eye / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005901:Glaucoma / Q000188:drug therapy; D009798:Ocular Hypertension / Q000188:drug therapy; D010758:Phosphorus / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D011817:Rabbits; D055672:Static Electricity
D002264:Carboxylic Acids; D050091:Dendrimers; D004337:Drug Carriers; D000644:Quaternary Ammonium Compounds; D010758:Phosphorus; D002354:Carteolol