Solid lipid nanoparticles as promising tool for intraocular tobramycin delivery: Pharmacokinetic studies on rabbits

Abstract

Eye drops are widely accepted as formulations for targeting the anterior segment notwithstanding their limitations in terms of bioavailability. The unique structure of the eye requires specially-designed formulations able to favor the pharmacokinetic profile of administered drugs, mainly minimizing the influence of ocular barriers. Nanotechnology-based delivery systems lead to significant technological and therapeutical advantages in ophthalmic therapy. The aim of the present study was to determine whether tobramycin as ion-pair incorporated in mucoadhesive Solid Lipid Nanoparticles (SLN) reaches the inner parts of the eye favoring drug activity. After technological characterization of the tobramycin entrapped SLN formulation (Tobra-SLN), a pharmacokinetic study in rabbits after topical instillation and intravenous administration of the formulation has been carried out. In addition, the intracellular activity of Tobra-SLN formulation against phagocytosed Pseudomonas aeruginosa was investigated. The SLN were spherical in shape, and showed a hydrodynamic diameter of about 80nm, a negative zeta potential (-25.7mV) with a polydispersity index of 0.15, representative of a colloidal dispersion with high quality, characterized by an unimodal relatively narrow size distribution. As demonstrated by FTIR and DSC, tobramycin ion-pair could be concentrated into lipid inner core of SLN, without interaction with the stearic acid, thus promoting a slow and constant drug release profile in the dissolution medium. Surprisingly, the drug concentration was significantly higher in all ocular tissues after ocular and intravenous administration of Tobra-SLN formulation with respect to reference formulations and only Tobra-SLN allowed the penetration of drug into retina. Furthermore, the use of Tobra-SLN resulted in both higher intraphagocytic antibiotic concentrations in polymorphonuclear granulocytes and greater bactericidal activity against intracellular Pseudomonas aeruginosa, probably due to the ability of Tobra-SLN to penetrate either into phagocytic cells, or alternatively to cross bacterial barrier. The present study broadens the knowledge on the use of SLN as carriers for ocular drug delivery to the posterior chamber and might open new avenues for treatment of ocular infections, representing a strategy to overcome the microbial resistance.

Assembling Surfactants-Mucoadhesive Polymer Nanomicelles (ASMP-Nano) for Ocular Delivery of Cyclosporine-A

“…They were housed in standard cages in a light-controlled room (10 h dark/14 h light cycle) at 19 ± 1 • C and 50 ± 5% relative humidity and were given a standard pellet diet and water ad libitum. During the experiments the rabbits were placed in restraining boxes to which they had been habituated in a room with dim lighting and were allowed to move their heads and eyes freely [33]. For in vivo studies the rabbits were used and treated according to the "Guide for the Care and Use of Laboratory Animals".…”

Ocular delivery of proteins and peptides: Challenges and novel formulation approaches

“…However, low drug-loading, burst-effect and rapid elimination by mononuclear phagocytic system (MPS) are some of the drawbacks of SLNs. Chetoni and co-workers demonstrated therapeutic concentrations of an antibiotic, tobramycin was achieved 3 hours in the retina and vitreous following topical and parentral SLN administrations [166, 167]. Cyclosporine-A loaded chitosan based SLNs have shown promising in vitro results with high permeation and biocompatibility in rabbit corneal endothelial cells [168].…”

Formulation and Characterization of Moxifloxacin Nanoparticles with Ion Exchange Resin

“…[52] CODEN (USA): JDDTAO reduction in administration frequency, reduced drug toxicity, and targeted delivery to specific eye tissues [12,13,14,15] . Polymeric nanoparticles are one of the promising formulations for ophthalmic delivery using various polymers such as Ethyl cellulose and Eudragit [16] , Chitosan, Sodium alginate, Poly-ε-caprolactone, Poly-L-lactide, and Poly-D, Llactide-co-glycolide [17,18] . Nanoemulsions using isopropyl myristate and triacetin have also been explored for ophthalmic application [19] .…”