Charged nanoparticles delivery to the eye using hydrogel iontophoresis.

Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Journal of Controlled Release (Impact Factor: 7.26). 04/2008; 126(2):156-61. DOI: 10.1016/j.jconrel.2007.11.016
Source: PubMed

ABSTRACT Ocular iontophoresis has been investigated for many years as a non-invasive technique for enhancing ionized drug penetration through ocular tissues. In this study we assessed the penetration of charged fluorescent nanoparticles into rabbit eyes using hydrogel iontophoresis. Particle distribution into ocular tissues and penetration efficiency of negative nanoparticles compared with positive nanoparticles was also evaluated. Cathodal and anodal iontophoretic administrations were performed using polyacrylic hydrogels loaded with charged nanoparticle suspension (20-45 nm), applying a current intensity of 1.5 mA for 5 min onto the cornea and sclera. At pre-set time points post treatment, eyes were dissected and tissues were evaluated for fluorescence intensity. Strong fluorescence evidence was observed at anterior and posterior ocular tissues. Negative particle distribution profile revealed fast uptake into the outer ocular tissues, within 30 min post treatment, followed by particle migration into the inner tissues up to 12 h post treatment. The positively charged particles demonstrated better penetration abilities into inner ocular tissues compared to the negatively charge particles. This work provides an opening for the development of a new ocular therapeutic pathway using iontophoresis of extended release drug-loaded charged nanoparticles.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Drug delivery to the eye is hampered by anatomical factors, including the corneal epithelium, the blood-aqueous barrier and the blood-retinal barrier. This review aims to outline the major routes of ocular drug delivery, including systemic, topical, periocular and intravitreal. The pharmacokinetics, the disadvantages and the clinical relevance of these drug delivery routes have been emphasised. Recent advances in surgical techniques, therapeutic approaches and material sciences have produced exciting new therapies for ocular diseases. The role of ophthalmic drug formulation in targeting the desired ocular tissue and enhancing drug delivery by the chosen route whilst minimising side effects is also discussed.
    Expert Opinion on Drug Delivery 04/2006; 3(2):275-87. DOI:10.1517/17425247.3.2.275 · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate in vitro and in vivo hydrogel-iontophoresis delivery of carboplatin to the eye. Iontophoresis was applied on agar gels resembling the eye using different current intensities and durations. Transscleral iontophoresis was performed on healthy rabbits, applying 0, 1, and 3 mA current for 10 min. Similar drug concentrations were obtained in all experimental groups, in in vitro and in vivo studies, regardless of the iontophoretic current applied. A 20-mm penetration depth was found for carboplatin at the agar model. High drug levels were found at the sclera and retina, while lower levels were found at ocular fluids. Carboplatin-iontophoretic application at the above conditions does not have an obvious advantage over passive penetration due to high diffusion properties and insufficient molecular charge. Passive carboplatin diffusion from loaded hydrogels inserted in the lower cul-de-sac should be further investigated as a potential clinical treatment for intraocular retinoblastoma.
    Current Eye Research 04/2008; 33(3):269-75. DOI:10.1080/02713680701871140 · 1.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.
    Current pharmaceutical design 02/2009; 15(23):2724-50. DOI:10.2174/138161209788923886 · 3.29 Impact Factor