title: Polyamidoamine dendrimer hydrogel for enhanced delivery of antiglaucoma drugs.
abstract: Dendrimer hydrogel (DH), made from ultraviolet-cured polyamidoamine dendrimer G3.0 tethered with three polyethylene glycol (PEG, 12,000 Da)-acrylate chains (8.1% w/v) in pH 7.4 phosphate buffered saline (PBS), was studied for the delivery of brimonidine (0.1% w/v) and timolol maleate (0.5% w/v), two antiglaucoma drugs. DH was found to be mucoadhesive to mucin particles and nontoxic to human corneal epithelial cells. DH increased the PBS solubility of brimonidine by 77.6% and sustained the in vitro release of both drugs over 56-72 hours. As compared to eye drop formulations (PBS-drug solutions), DH brought about substantially higher human corneal epithelial cells uptake and significantly increased bovine corneal transport for both drugs. DH increased timolol maleate uptake in bovine corneal epithelium, stroma, and endothelium by 0.4- to 4.6-fold. This work demonstrated that DH can enhance the delivery of antiglaucoma drugs in multiple aspects and represents a novel platform for ocular drug delivery.
  
  
  BACKGROUND
  Dendrimer hydrogel was studied as agent for simultaneous delivery of two anti-glaucoma drugs, one hydrophobic and one hydrophilic. Superiority over standard PBS-based formulation was clearly demonstrated for both drugs. The work may be a novel platform for ocular drug delivery.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, Virginia 23284, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Holden
authors.forename: Puneet
authors.initials: P
authors.lastname: Tyagi
authors.forename: Ashish
authors.initials: A
authors.lastname: Thakur
authors.forename: Rajendra
authors.initials: R
authors.lastname: Kadam
authors.forename: Gajanan
authors.initials: G
authors.lastname: Jadhav
authors.forename: Uday B
authors.initials: UB
authors.lastname: Kompella
authors.forename: Hu
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D000068438:Brimonidine Tartrate; D002417:Cattle; D002460:Cell Line; D050091:Dendrimers / Q000494:pharmacology*; D004338:Drug Combinations; D016503:Drug Delivery Systems; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000737:chemistry; D011810:Quinoxalines / Q000494:pharmacology*; D013999:Timolol / Q000493:pharmacokinetics*
chemical_list: D050091:Dendrimers; D004338:Drug Combinations; D009883:Ophthalmic Solutions; C104700:PAMAM Starburst; D011810:Quinoxalines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000068438:Brimonidine Tartrate; D013999:Timolol