Intravitreal delivery

Marketed Drugs or Drugs Under Development for Intravitreal Delivery... 

Thus, there exist a variety of predominantly acute edematous retinal disorders that may be amenable for treatment with an intravitreous injection of INS37217. For treatment of chronic conditions such as cystoid or diabetic macular edema, alternative means of intravitreous delivery, such as intravitreous insert or implant or a sustained-release formulation, will likely be required. 

Chhablani et al. showed that in oxidized PSi covalently loaded daunorubicin demonstrated sustained intravitreal release for 3 months without any evidence of toxicity, while physisorbed daunorubicin was released within 2 weeks and localized retinal toxicity were observed due to high daunorubicin concentration. Wu et al. added a new functionality to PSi dmg delivery system (Wu et al. 2011). They used 1-dimensional porous silicon photonic crystal in intravitreal delivery. The reflectance spectrum of the crystal (i.e., color) changed from red to green as daunombicin was releasing enabling real-time monitoring of the drag release proeess. These types of multifunctional delivery systems based on versatile properties of PSi are expeeted to be published much more in future. 

Administration route 1 Bioactive 1 Biocompatibility 1 Biodegradable porous silicon 1 Bioresorbable property 1 Composite structures 5 Degradation products 5 Drug delivery 1 In vitro drug 2 In vivo drug 2 Intravenous delivery 4 Intravitreal delivery 4 Microparticles 1 Nanoparticles 1 Oral delivery 2 Peptide 3... 

Subtenon High vitreal drug levels, relatively noninvasive, fewer complications unlike intravitreal delivery Retinal pigmented epithelium, chemosis, subconjunctival hemorrhage... 

A Bochot, P Couvreur, E Fattal. Intravitreal administration of antisense oligonucleotides potential of liposomal delivery. Prog Retin Eye Res 19(2) 131—147, 2000. 

An alternative to direct intravitreal injection is to use a noninvasive method of ASO delivery employing iontophoresis. The advantage of using low current density iontophoresis is that the ASO intraocular distribution will allow for therapeutic concentrations to be achieved across a large number of tissues, including the anterior uvea and the cornea as well as neural retinal areas. Voigt et al. [9] evalu-... 

Intraocular drag delivery is more difficult to achieve practically. Research, as described below, is concentrating on the development of intravitreal injections and the use of intraocular implants to improve... 

The main drawbacks associated with liposomes are their short shelf life and difficulty in storage, limited drag-loading capacity and instability on sterilization and finally, transient blurring of vision after an intravitreal injection. Despite these disadvantages, they have a potential as drag delivery systems as they are composed of substances that are non-toxic and totally biodegradable. 

Sustained delivery of ophthalmic medications is a novel approach in treating chronic intraocular infections in conditions where systemic administration is accompanied by undesirable side-effects and repeated intravitreal injections carry the risk of infection. The administration of medications by implants or depot devices is a very rapidly developing technology in ocular therapeutics. The various types of implant and mechanisms of drug release have been discussed in general in Chapter 4. 

Bochot, A., Couvreur, P., and Fattal, E. (2000), Intravitreal administration of antisense oligonucleotides Potential of liposomal delivery, Prog. Retin. Eye Res., 19, 131-147. 

Kawakami, S., Yamamura, K., Mukai, T., Nishida, K., Nakamura, J., Sakaeda, T., Nakashima, M., and Sasaki, H. (2001), Sustained ocular delivery of tilisolol to rabbits after topical administration or intravitreal injection of lipophilic prodrug incorporated in liposomes, /. Pharm. Pharmacol., 53,157-161. 

On the other hand, the most efficient method for drug delivery to the posterior chamber of the eye so far has been intravitreal injection. This chapter focuses on the topical application of drugs to the surface of the eye and discusses the most recent formulation approaches in this area. 

Various colloidal systems have been studied for use as potential ophthalmic delivery systems, including liposomes and nanoparticles. Liposomes are bioerodible and biocompatible systems consisting of microscopic vesicles composed of lipid bilayers surrounding aqueous compartments. Liposomes have demonstrated prolonged drug effect at the site of action but with reduced toxicity. Ophthalmic studies have included topical, subconjunctival, and intravitreal administration, but no commercial preparations are currently available for ophthalmic use. 

The success of intravitreal implants, such as achieved with ganciclovir, has renewed interest in developing an intravitreal corticosteroid implant to further enhance the intravitreal route of administration, thus reducing the need for multiple injections. Bausch and Lomb and Control Delivery Systems have developed an intravitreal implant that can deliver the corticosteroid fluocinolone acetonide (Retrisert) to posterior eye tissue for up to 3 years. The implant, which was approved in 2005 by the U.S. Food and DrugAdministration (FDA), delivers 0.59 or 2.1 mg of fluocinolone acetonide. The long-term ocular side effects of this device are unknown at this time. 

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