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Conducting Polymers for Ophthalmic Applications
Published in Ram K. Gupta, Conducting Polymers, 2022
Two main approaches can be identified in the treatment of ocular disorders: (a) delivery of drug molecules to the relevant tissues and (b) surgical procedure for repairing or replacing damaged tissue. Various methods are available for drug delivery to the eye. However, it has major deficiencies in the treatment of diseases that occur primarily in the posterior segment [10]. Intraocular (intracameral and intravitreal), topical, and systemic routes are the most common ocular drug delivery systems (ODDS). The anterior and posterior segments can both be treated with the intracameral approach. Applications to the anterior chamber, in particular, are conducted during surgery (i.e., cataract surgery). For the posterior segment, despite its relatively high bioavailability, some infections may develop such as retinal detachment or hemorrhage, and injections need to be repeated [11, 12]. The intravitreal route includes the injection of the drug directly in the vitreous humor, thus a significant way for the treatment of posterior segment diseases. Drug distribution in the vitreous is regulated by a variety of parameters, including the drug's molecular weight (MW), and is rarely uniform [6].
Ocular Drug Delivery Nanosystems: Recent Developments and Future Challenges
Published in Costas Demetzos, Stergios Pispas, Natassa Pippa, Drug Delivery Nanosystems, 2019
Elena A. Mourelatou, Yiannis Sarigiannis, Christos C. Petrou
Regarding the treatment of anterior segment diseases (keratitis, conjunctivitis, dry eye syndrome [DES], etc.), topical administration is the most commonly used route (Fig. 4.1), where formulations such as solutions, suspensions, ointments, and hydrogels are applied [4]. Although this route is characterized by high patient compliance (no pain), low production cost, and easy formulation and production processes, it suffers from low bioavailability, with less than 5% of the administered dose being able to overcome the ocular barriers and reach the target site. This creates the need for repeated administration in order to achieve a therapeutic effect, which leads to poor patient compliance and side effects caused by systemic absorption of the administered drug [5, 6]. On the other hand, the treatment of posterior segment diseases (glaucoma, age-related macular degeneration [AMD], uveitis, diabetic retinopathy [DR], endophthalmitis, diabetic macular edema, etc.) requires more invasive approaches, such as intravitreal, subconjunctival, subtenon, and posterior juxtascleral routes (Fig. 4.1), with the most prevalent being intravitreal injection [5]. The latter, especially when repeated at regular intervals for maintaining the desired drug’s concentration (e.g., for glaucoma treatment), is associated with significant patient discomfort and nonconformance, as well as sight-threatening complications, including a risk of infections, endophthalmitis, retinal tear or detachment, lens damage, and cataract [2, 7]. Reaching the posterior segment through systemic administration (oral and intravenous) is impractical, since the volume of the eye is extremely small compared to the whole body and the presence of blood retinal barriers limits its accessibility [3].
Development of Ophthalmic Formulations
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Paramita Sarkar, Martin Coffey, Mohannad Shawer
Topical eye drop administration is mainly suitable for the treatment of ocular conditions in the anterior segment of the eye. Targeting the posterior segment of the eye presents a far greater challenge and represents an area of unmet medical needs. Many of the newer drugs aimed at treating conditions such as diabetic retinopathy and AMD are administered via repeated intravitreal injections. Alternative approaches that would improve patient acceptance such as biodegradable inserts or micro- and nanoparticulate delivery systems present a growing field in the area of ophthalmic drug delivery.
Design of a navigational catheter system for the targeted delivery of therapeutics within the suprachoroidal space
Published in Journal of Medical Engineering & Technology, 2020
Anthony E. Felder, Yannek I. Leiderman, Matthew Tomback, Aaron Chicano, Manuela Burek, Xenon Arendovich, Kimberlee Wilkens, Charles Frisbie, Cristian Luciano, Levi N. Kanu, Peter Pfanner
Diseases of the retina, such as age-related macular degeneration [1] and diabetic retinopathy [2], are common causes of blindness. While the pathophysiology of these diseases varies, their location in the posterior segment has historically made drug delivery challenging. These diseases, or stages thereof, are commonly treated by repeated intravitreal injections [3]. However, this method precludes the targeted delivery of novel therapies like retinal implants [4], extracellular scaffolds [5,6], adeno-associated viral vectors [7,8], cellular transplants [9,10], and other genetic therapies [11] due to restrictions on size or location of the injected payload. Another potential delivery medium to the posterior segment is through the suprachoroidal space (SCS) [12]. The SCS spans the perimeter of the ocular globe and can be accessed via a trans-scleral approach with blunt dissection of the neighbouring chorioretinal and scleral tissues. To date, the SCS has been utilised for many purposes, including drug delivery [13–15], retention drainage of the anterior chamber [16], drainage of choroidal effusions [17], and repair of retinal detachment [18]. Moreover, drug delivery within the SCS can increase the efficacy and bioavailability of the administered therapeutic [19,20], potentially reducing adverse side effects caused by delivery to other ocular tissues.
En face swept-source optical coherence tomography angiography choroidal vasculography (CVG) a tool to discriminate choroidal abnormalities in polypoidal choroidal vasculopathy
Published in Expert Review of Medical Devices, 2021
Juan D. Arias, M. Margarita Parra, Andrea T. Hoyos, Francisco Arango, Eduardo J. Viteri, J. Fernando Arevalo
Naïve subjects were included. All patients were treated with anti-VEGF therapy, including Bevacizumab (Avastin, Genentech, South San Francisco, California, USA), Ranibizumab (Lucentis, Genentech, South San Francisco, California, USA) and Aflibercept (Eylea, Regeneron, Tarrytown, NY, USA). All patients received three monthly intravitreal injections. Evaluation after treatment was performed one month after the last intravitreal injection.
Enhancing the efficacy of fluocinolone acetonide by encapsulating with PLGA nanoparticles and conjugating with linear PEG polymer
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Joyce Pinto, Madiha Ahmad, Bharath Raja Guru
Fluocinolone acetonide is a glucocorticoid [1] frequently used for the treatment of ocular inflammations in the posterior chamber such as uveitis or age related macular degeneration [2]. Most long term treatment methods for treating ocular inflammation in the vitreous chamber involve intravitreal injections [3] with the intention of achieving therapeutic concentrations of the drug without systemic toxicity. Frequent invasive therapy can lead to retinal detachment, haemorrhage or endophthalmitis [4]. Therefore, methods to achieve therapeutic value to combat ocular inflammation are advocated. It has been reported that drug conjugates and PLA nanoparticles move towards the posterior part of the eye and remain there for months and release its encapsulated components whereas free drug/fluorescent molecule diffused to the site gradually only for a limited time period [5]. Raymond Iezzi et al. showed FA conjugated hydroxyl-terminated polyamidoamine (PAMAM) dendrimers selectively localized in diseased site to give therapeutic effect for a month by inhibiting retinal degeneration in RCS rat model [6]. Therefore nanoparticles (NPs) encapsulated with drug and drug conjugates offer advantages to reach the posterior region and persists at the site for long durations apart from controlled release of the active agent [7, 8]. Nanoparticles may also help by increasing drug stability over longer periods of time. In the last few decades, biodegradable polymeric NPs and biocompatible implants have shown potential as drug delivery devices for ocular treatment. Some of the initial biodegradable polymeric NPs for ocular delivery were published by Vincent et al. [9]. They evaluated polybutylcyanoacrylate NPs loaded with progesterone. Suzanne Einmahl et al. showed that poly(ortho ester) NPs injected into the suprachoroidal space of the rabbit eye were present up to 3 weeks [10]. Yandrapu et al. worked on PLA NPs within PLGA based microparticles for sustained release of bevacizumab and further studied in a rat model detecting it for up to 2 months [11]. Pan et al. studied dexamethasone sodium phosphate loaded PLGA (50:50 and MW: 3.2kDa) NPs prepared by solvent diffusion method with in vitro drug release over 15 days [12]. Retisert®, an FDA approved intravitreal implant loaded with FA (0.59 mg) composed of polyvinyl alcohol (PVA) with a release of up to 2–2.5 years [4], however the implant has had drawbacks with post implantation cases of cataract and increased intraocular pressure [13]. Iluvien®, another intravitreal insert from Alimera Sciences, was developed for diabetic macular edema, is made from polyimide and PVA and giving a sustained release up to 3 years [14]. The implants are non-biodegradable and remain within the eye for long time after the drug reservoir has depleted can lead to further issues for the patient.