Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide.
The purpose of this study was to determine the influence of a controlled incremental increase in size, molecular weight and number of amine, carboxylate and hydroxyl surface groups in several series of poly(amidoamine) (PAMAM) dendrimers for controlled ocular drug delivery. The duration of residence time was evaluated after solubilization of several series of PAMAM dendrimers (generations 1.5 and 2-3.5 and 4) in buffered phosphate solutions containing 2 per thousand (w/v) of fluorescein. The New Zealand albino rabbit was used as an in vivo model for qualitative and quantitative assessment of ocular tolerance and retention time after a single application of 25 microl of dendrimer solution to the eye. The same model was also used to determine the prolonged miotic or mydriatic activities of dendrimer solutions, some containing pilocarpine nitrate and some tropicamide, respectively. Residence time was longer for the solutions containing dendrimers with carboxylic and hydroxyl surface groups. No prolongation of remanence time was observed when dendrimer concentration (0.25-2%) increased. The remanence time of PAMAM dendrimer solutions on the cornea showed size and molecular weight dependency. This study allowed novel macromolecular carriers to be designed with prolonged drug residence time for the ophthalmic route.
Vandamme
Th F
TF
UMR 7514, Laboratoire de Chimie Bioorganique, Faculté de Pharmacie, Université Louis Pasteur, 74, Route du Rhin-B.P.60024-, 67401 Illkirch Cedex, France. vandamme@pharma.u-strasbg.fr
Brobeck
L
L
D000588:Amines / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D005123:Eye / Q000187:drug effects; D008297:Male; D009757:Nylons / Q000737:chemistry / Q000494:pharmacology*; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D010862:Pilocarpine / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D014331:Tropicamide / Q000008:administration & dosage* / Q000737:chemistry
D000588:Amines; D009757:Nylons; D009883:Ophthalmic Solutions; D010862:Pilocarpine; D014331:Tropicamide