A review on recent drug delivery systems for posterior segment of eye

Nayak, Kritika; Misra, Manju

doi:10.1016/j.biopha.2018.08.138

Cited by 176 publications

(121 citation statements)

References 116 publications

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“…The vitreous humor has a volume of 4 mL in the human eye [137], and it consists of a negatively charged 3D matrix based on collagen and HA [2,137,143]. The mobility of large particles is hindered due to steric effects, because the limiting mesh size of the vitreous is 550 nm [137,144,150,151].…”

Section: Intravitreal Administrationmentioning

confidence: 99%

“…For example, Formica et al [1] reviewed the properties of natural polymers and the use of natural polymers for the preparation of nanocarriers for topical ocular drug administration. Similarly, Nayak et al [2] discussed the properties of liposomes, emulsions, nano-and microspheres, and conjugates as ophthalmic drug formulations, although the topical and intravitreal systems used in that study were based on non-natural biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and polyvinyl alcohol. Tsai et al [3] examined the use of the polysaccharide chitosan in eye drops for DNA delivery to the eye, but no reviews have yet explored the effectiveness of drug delivery to various eye segments in terms of the properties of polysaccharides and their derivatives, nor have ophthalmic drug delivery systems based on polysaccharides been described in detail.…”

Section: Introductionmentioning

confidence: 99%

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Polysaccharides in Ocular Drug Delivery

et al. 2019

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Polysaccharides, such as cellulose, hyaluronic acid, alginic acid, and chitosan, as well as polysaccharide derivatives, have been successfully used to augment drug delivery in the treatment of ocular pathologies. The properties of polysaccharides can be extensively modified to optimize ocular drug formulations and to obtain biocompatible and biodegradable drugs with improved bioavailability and tailored pharmacological effects. This review discusses the available polysaccharide choices for overcoming the difficulties associated with ocular drug delivery, and it explores the reasons for the dependence between the physicochemical properties of polysaccharide-based drug carriers and their efficiency in different formulations and applications. Polysaccharides will continue to be of great interest to researchers endeavoring to develop ophthalmic drugs with improved effectiveness and safety.

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Section: Intravitreal Administrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polysaccharides in Ocular Drug Delivery

et al. 2019

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“…23 Also, the injected aflibercept-DDS showed no migration into the anterior chamber and no anterior and posterior uveitis up to 6 months for long-term IVT delivery of VEGF, which contrasts with other recent studies of DDS systems. [32][33][34] A recent study of IVT injection of PLGA microspheres in cynomolgus macaques describes a moderate to severe inflammatory response within 1 month postinjection that included corneal edema, corneal neovascularization, aqueous flare, vitreous cells, iridal hyperemia, posterior synechiae, inflammatory cells on the lens, and cystoid macular edema that necessitated euthanasia for animal welfare purposes. 34 Although it was observed in this study that smaller microspheres (20 μm in diameter) caused the most severe reaction, whereas the larger PLGA rods (0.9 × 3.7 mm) were well tolerated, 34 we highlight that the encapsulation of the 7 μm PLGA microspheres in the hydrogel is likely responsible for the minimal observed inflammation in the present study.…”

Section: Discussionmentioning

confidence: 99%

Safety and Biocompatibility of Aflibercept-Loaded Microsphere Thermo-Responsive Hydrogel Drug Delivery System in a Nonhuman Primate Model

Kim

Kang-Mieler

Liu

et al. 2020

Trans. Vis. Sci. Tech.

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Citation: Kim S, Kang-Mieler JJ, Liu W, Wang Z, Yiu G, Teixeira LBC, Mieler WF, Thomasy SM. Safety and biocompatibility of aflibercept-loaded microsphere thermo-responsive hydrogel drug delivery system in a nonhuman primate model. Trans Vis Sci Tech. 2020;9(3):30, https://doi.org/10.1167/tvst.9.3.30Purpose: To evaluate the safety and tolerability of a microsphere thermo-responsive hydrogel drug delivery system (DDS) loaded with aflibercept in a nonhuman primate model. Methods:A sterile 50 μL of aflibercept-loaded microsphere thermo-responsive hydrogel-DDS (aflibercept-DDS) was injected intravitreally into the right eye of 10 healthy rhesus macaques. A complete ophthalmic examination, intraocular pressure (IOP) measurement, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and electroretinogram were performed monthly for 6 months. One macaque was euthanized monthly, and the enucleated eyes were submitted for measurement of bioactive aflibercept concentrations. Four eyes were submitted for histopathology.Results: Injected aflibercept-DDS was visualized in the vitreous until 6 months postinjection. No abnormalities were observed in the anterior segment, and IOP remained within normal range during the study period. A small number of cells were observed in the vitreous of some macaques, but otherwise the remainder of the posterior segment examination was normal. No significant changes in retinal architecture or function as assessed by SD-OCT and histology or full-field electroretinography, respectively, were observed. A mild, focal foreign body reaction around the injectate was observed with histology at 6 months postinjection. A mean of 2.1 ng/μL of aflibercept was measured in the vitreous. Conclusions:Intravitreally injected aflibercept-DDS achieved controlled, sustained release of aflibercept with no adverse effects for up to 6 months in the eyes of healthy rhesus macaques.Translational Relevance: Aflibercept-DDS may be a more effective method to deliver bioactive antivascular endothelial growth factor agents than current practice by reducing the frequency of intravitreal injections and providing controlled drug release.

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“…[4][5][6][7] By enabling predictable dosing to aid compliance and by ensuring continuous intraocular therapeutic levels, a device for sustained protein delivery for BotE would not only reduce the treatment burden, but would also have the potential to maximize and maintain vision benefits for patients with retinal diseases in clinical practice with these widely used drugs. Specifically, a sustained release device requiring dosing less than four times a year, as opposed to [6][7][8][9][10][11][12] times per year as in current practice, would meaningfully improve patient care.…”

Section: Introductionmentioning

confidence: 99%

“…Despite years of efforts and advances in research, preclinical, and clinical development, sustained delivery systems for protein therapeutics remain an unmet need [1][2][3] : among ocular drug delivery technologies that have reached clinical trials, the Port Delivery System is the only technology to accommodate a protein therapeutic. 8 Dose, duration, and stability are the three primary challenges in sustained protein release, particularly for intraocular delivery. 3,9 Protein therapies for BotE treatment require repeated bolus doses as frequent as 0.5 mg per month (ranibizumab) or 2 mg every 2 months (aflibercept).…”

Section: Introductionmentioning

confidence: 99%

Device design methodology and formulation of a protein therapeutic for sustained release intraocular delivery

Schlesinger

Bernards

Chen

et al. 2018

Bioengineering & Transla Med

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Despite years of effort, sustained delivery of protein therapeutics remains an unmet need due to three primary challenges – dose, duration, and stability. The work presented here provides a design methodology for polycaprolactone reservoir‐based thin film devices suitable for long‐acting protein delivery to the back of the eye. First, the challenge of formulating highly concentrated protein in a device reservoir was addressed by improving stability with solubility‐reducing excipients. Next, predictive correlations between design parameters and device performance were developed to provide a methodology to achieve a target product profile. Prototype devices were designed using this methodology to achieve desired device size, release rate, therapeutic payload, and protein stability, assessed by in vitro studies. Finally, prototype tolerability was established in a non‐human primate model. The design methodology presented here is widely applicable to reservoir‐based sustained delivery devices for proteins and provides a general device design framework.

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A review on recent drug delivery systems for posterior segment of eye

Cited by 176 publications

References 116 publications

Polysaccharides in Ocular Drug Delivery

Polysaccharides in Ocular Drug Delivery

Safety and Biocompatibility of Aflibercept-Loaded Microsphere Thermo-Responsive Hydrogel Drug Delivery System in a Nonhuman Primate Model

Device design methodology and formulation of a protein therapeutic for sustained release intraocular delivery

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