Implants for drug delivery to the posterior segment of the eye: A focus on stimuli-responsive and tunable release systems

Yasin, M. Naveed; Svirskis, Darren; Seyfoddin, Ali; Rupenthal, Ilva D.

doi:10.1016/j.jconrel.2014.09.030

Cited by 132 publications

(101 citation statements)

References 138 publications

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“…Seeking to overcome this negative scenario, research has been dedicated to developing new drug delivery systems, such as polymeric implants with the overall goal to be more selective and achieve favorable bioavailability profiles through sustained releasing of the therapeutic cargo [27,28]. Such systems offer many advantages, including favorable patient compliance, biocompatibility, predictable biodegradation kinetic and mechanical resistance in various intravitreal applications [29–31]. In order to mitigate the cumulative risks associated with repeated intravitreal injections, some implantable polymeric systems have been approved by FDA and currently available, for example: Ozurdex® (Dexamethasone Intravitreal Implant); Iluvien® (Fluocinolone acetonide intravitreal implant) and Triesence® (Triamcinolone acetonide).…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenic activity of PLGA-Lupeol implants for potential intravitreal applications

Soares

Oliveira

Barcelos

et al. 2017

Biomedicine & Pharmacotherapy

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Uncontrolled angiogenesis is directly associated with ocular diseases such as macular degeneration and diabetic retinopathy. Implantable polymeric drug delivery systems have been proposed for intravitreal applications and in the present work, we evaluated the antiangiogenic potential of PLGA ocular implants loaded with the triterpene lupeol using in vitro and in vivo models. The drug/polymer physiochemical properties of the lupeol-loaded PLGA were validated as functionally similar using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Interestingly, in an in vitro culture system, lupeol (100μg/mL and 250μg/mL) was capable to inhibited the proliferation as well as the migration of Human Umbilical Vein Endothelial Cells (HUVEC), without interfering in cell viability, promoting a significant reduction in the percentage of vessels (39.41% and 44.12%, respectively), compared with the control group. In vivo test, by using the chorioallantoic membrane (CAM) model, lupeol-loaded PLGA ocular implants showed antiangiogenic activity comparable to the FDA-approved anti-VEGF antibody Bevacizumab. Overall, our results suggest lupeol-loaded PLGA ocular implants were able to inhibit the angiogenic process by impairing both proliferation and migration of endothelial cells.

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Section: Introductionmentioning

confidence: 99%

Antiangiogenic activity of PLGA-Lupeol implants for potential intravitreal applications

Soares

Oliveira

Barcelos

et al. 2017

Biomedicine & Pharmacotherapy

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“…1,2 To treat these disorders, most drugs need sustained and effective delivery to the posterior segment of the eye. 3 This part of the eye is composed of a blood-retinal barrier and an inner retinal limiting membrane that are relatively impermeable to many therapeutic agents. To improve the effectiveness of the drugs, invasive local therapy such as intravitreal injection is generally required.…”

Section: Introductionmentioning

confidence: 99%

Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections

Xu¹,

Xu²,

Liu³

et al. 2016

IJN

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To visually trace the diffusion and biodistribution of amphiphilic cation micelles after vitreous injection, various triblock copolymers of monomethoxy poly(ethylene glycol)–poly(ε-caprolactone)–polyethylenimine were synthesized with different structures of hydrophilic and hydrophobic segments, followed by labeling with near-infrared fluorescent dye Cyanine5 or Cyanine7. The micellar size, polydispersity index, and surface charge were measured by dynamic light scattering. The diffusion was monitored using photoacoustic imaging in real time after intravitreal injections. Moreover, the labeled nanoparticle distribution in the posterior segment of the eye was imaged histologically by confocal microscopy. The results showed that the hydrophilic segment increased vitreous diffusion, while a positive charge on the particle surface hindered diffusion. In addition, the particles diffused through the retinal layers and were enriched in the retinal pigment epithelial layer. This work tried to study the diffusion rate via a simple method by using visible images, and then provided basic data for the development of intraocular drug carriers.

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“…It contains 60 μg of dexamethasone incorporated into a poly(lactic-glycolic)-acid (PLGA) matrix, which controls the release of dexamethasone over 7 days, achieving higher intraocular drug levels than with conventional dexamethasone drops [47]. Ozurdex ® , Retiser and Iluvien ® are all ocular implants which release corticosteroids over 6, 30 and 36 months, respectively, and are indicated for use in macular oedema and uveitis [7]. Ozurdex ® is based on NOVADUR ® CR platform, where dexamethasone is combined with the biodegradable PLGA to form a small rod-shaped implant.…”

Section: Inflammationmentioning

confidence: 99%

“…Current research into 'smart' CR systems investigates the ability to increase or decrease drug release in situ in response to an external trigger or using a biological marker forming a closed-loop and self-regulating drug delivery system [7]. Application of these smart CR systems in post-surgical settings will have the advantage of tuning drug delivery in direct response to an individual's changing needs.…”

Section: Introductionmentioning

confidence: 99%

Controlled release drug delivery systems to improve post-operative pharmacotherapy

Bhusal

Harrison

Sharma

et al. 2016

Drug Deliv. and Transl. Res.

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Over 230 million surgical procedures are conducted worldwide each year with numbers increasing. Pain, undesirable inflammation and infection are common complications experienced by patients following surgery. Opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anaesthetics (LAs) and antibiotics are the commonly administered drugs peri-operatively to manage these complications. Post-operative pharmacotherapy is typically achieved using immediate-release dosage forms of drugs, which lead to issues around fluctuating plasma concentrations, systemic adverse effects and poor patient adherence. Controlled release (CR) systems for certain medicines including opioids, NSAIDs and antibiotics have demonstrably enhanced treatment efficacy in the post-surgical setting. However, challenges remain to ensure patient safety while achieving individual therapeutic needs. Newer CR systems in the research and development pipeline have a high level of control over medicine release, which can be initiated, tuned or stopped on-demand. Future systems will self-regulate drug release in response to biological markers providing precise individualized therapy. In this review, we cover currently adopted CR systems in post-operative pharmacotherapy, including drug eluting medical devices, and highlight a series of examples of novel CR technologies that have the potential for translation into post-surgical settings to improve medication efficacy and enhance post-surgical recovery.

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Implants for drug delivery to the posterior segment of the eye: A focus on stimuli-responsive and tunable release systems

Cited by 132 publications

References 138 publications

Antiangiogenic activity of PLGA-Lupeol implants for potential intravitreal applications

Antiangiogenic activity of PLGA-Lupeol implants for potential intravitreal applications

Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections

Controlled release drug delivery systems to improve post-operative pharmacotherapy

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