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Biodegradable PLA nanoparticles (140 nm) administered intravitreally have been shown to localize in the retinal pigment epithelium (Bourges et al. 2003), and coating nanoparticles with PEG has been reported to enhance the therapeutic efficacy of treatment for ocular diseases such as autoimmune uveoretinitis (De Kozak et al. 2004).
Studies on nonbiodegradable drug-impregnated contact lenses for the sustained release of ocular drugs have been reported by several investigators (Alvarez-Lorenzo et al. 2006; Schultz et al. 2009; Xinming et al. 2007). Soft contact lenses composed of nonbiodegradable hydrogels of poly(2-hydroxyethylmethacrylate) (PHEMA) or hydroxyethylmethacrylate (HEMA) copolymerized with other monomers such as methacrylic acid, acetone acrylamide, and vinyl pyrrolidone are typically used for drug impregnation. The amount of drug that can be loaded into contact lenses is generally low, and drug release is usually rapid and poorly controlled. Entrapping the drug in a biodegradable nanoparticle prior to incorporation into the contact lens may be useful for sustaining drug release (Conway 2008).
9.7 Conclusions
Biodegradable polymer-based drug delivery systems display a variety of characteristics that make them ideally suited for the treatment of ocular diseases. Biodegradable drug delivery systems represent a promising solution to many of the limitations of conventional techniques for ocular drug delivery, particularly in the treatment of sightthreatening retinal diseases. Several of the polymers used in current biodegradable drug delivery systems have been demonstrated to be biocompatible and to have an acceptable ocular safety profile. Additional polymers at the experimental stage of development are being explored for use in biodegradable drug delivery systems and are being evaluated in preclinical and preliminary clinical studies. Biodegradable polymers are versatile in that they can be used to construct delivery systems with customized release profiles to optimize drug delivery for the treatment of various diseases of the posterior and anterior segments of the eye. In addition to being useful for the delivery of novel therapeutic agents, biodegradable drug delivery systems are being explored as a means for delivering already-established drugs that are not sufficiently effective when administered by conventional routes of administration. Ongoing clinical research is being conducted to determine the efficacy and safety of biodegradable drug delivery systems in a variety of ocular diseases, and promising new additions to the therapeutic armamentarium can be expected in the future.
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Chapter 10
Microparticles as Drug Delivery Systems for the Back of the Eye
Rocío Herrero-Vanrell
Abstract Treatment of vitreoretinal disorders often include repeated intraocular injections to achieve effective levels of the active substance in the target site. Intraocular drug delivery systems (IDDS) are considered an alternative to multiple injections as they release the encapsulated drug over long periods of time. Among them, biodegradable microparticles are very useful for intraocular administration because they can be injected as a conventional suspension without surgical procedures, to release the active substance over weeks or months. Microparticles can be loaded with different drugs useful to treat different pathologies affecting the back of the eye such as proliferative vitreoretinopathy, age-related macular degeneration, cytomegalovirus retinitis, diabetic retinopathy, endophthalmitis, glaucoma, herpes infection, macular edema, retinal vein occlusion, retinitis pigmentosa, and uveitis. Administration of microparticles can be performed by periocular, intravitreal, subretinal, or other intraocular routes to treat vitreoretinal disorders. Generally, microparticles are loaded with one active substance. Recently, biodegradable microparticles loaded with more than one drug (“combo microparticles”) are being developed. Moreover, biodegradable microspheres are potential tools for retinal repair in combination with retinal progenitor cells.
Abbreviations
PLA |
Poly(lactic) acid |
PGA |
Poly(glycolic) acid |
PLGA |
Poly(lactic-co-glycolic) acid |
GPC |
Gel permeation chromatography |
R. Herrero-Vanrell (*)
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Avda Complutense s/n, Complutense University, 28040 Madrid, Spain
e-mail: rociohv@farm.ucm.es
U.B. Kompella and H.F. Edelhauser (eds.), Drug Product Development for the Back of the Eye, 231 AAPS Advances in the Pharmaceutical Sciences Series 2, DOI 10.1007/978-1-4419-9920-7_10,
© American Association of Pharmaceutical Scientists, 2011