Purchase this article with an account.
U. B. Kompella, C. Durairaj, R. S. Kadam, J. W. Chandler; Nanosized Dendrimeric Polyguanidilyated Translocators for Enhanced Ocular Delivery of Gatifloxacin. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3795.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Dendrimeric polyguanidilyated translocators (DPTs) are a novel class of hyperbranched dendrimers with cell penetrating surface guanidine groups, flexible branches, and a core available for functionalization. DPTs efficiently translocate molecules across biological barriers. The purpose of this study was to evaluate the in vivo delivery of gatifloxacin by DPTs.
A DPT formulation capable of enhancing the solubility of gatifloxacin was developed. Cell penetration of the formulation was assessed in human corneal epithelial cells. The potential of the formulation to increase gatifloxacin permeability was assessed in bovine sclera-choroid-RPE (SCRPE). In vitro antibacterial activity of DPT formulation was evaluated against methicillin resistant S. aureus organism (MRSA) by the "time to kill" assay. In vivo pharmacokinetics of gatifloxacin after topical administration of dendrimer formulation (two 50 µl drops 5 mins apart) were assessed in male NZW rabbits and the drug in eye tissues was quantified using an LC-MS/MS assay.
The optimized DPT formulation had 4-fold higher gatifloxacin content (1.2% vs. 0.3% in Zymar) and a pH of 5.9, with no preservative. Rapid entry of dendrimer was observed within 5 min in human corneal epithelial cells. Also, the dendrimer formulation increased the scleral permeability of gatifloxacin by 40%. The time to kill assay indicated a 3 times faster killing rate with DPT formulation when compared to plain gatifloxacin. In vivo studies indicated high drug levels in cornea, conjunctiva sclera, and aqueous humor (AH). Drug levels were detectable in all these tissues as well as vitreous humor (VH) till 24 h. DPT formulation resulted in higher AUC levels (11.88 fold in conjunctiva; 2.62 fold in cornea; 3.74 fold in AH) when compared with 0.3% Zymar.
DPT formulations enhance the solubility as well as permeability of ophthalmic drugs such as gatifloxacin. DPT formulation improves gatifloxacin activity by decreasing the time to kill MRSA. Once daily dosing of DPT formulation maintains high drug levels till 24 h in target tissues.
This PDF is available to Subscribers Only