Research progress of in-situ gelling ophthalmic drug delivery system

Wu, Yumei; Liu, Yuanyuan; Li, Xinyue; Kebebe, Dereje; Zhang, Bing; Ren, Jing; Lü, Jun; Li, Jiawei; Du, Shouying; Liu, Zhidong

doi:10.1016/j.ajps.2018.04.008

Cited by 196 publications

(143 citation statements)

References 79 publications

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“…Among these systems, in situ gels containing stimuli-responsive polymers (such as pH-, thermo-, or ion-sensitive polymers) are one of the most promising approaches to improve the retention time of drugs. 49 Thus far, thermo-responsive polymers have been applied for a variety of ophthalmic applications. For the anterior segment, thermo-responsive in situ forming gels containing antihistamine or anti-inflammatory drugs have been tested to improve transcorneal absorption of drugs.…”

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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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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“…They benefit from changes in physical, biological or chemical cues, undergoing physicochemical changes in the presence of even minor changes in their immediate environment [ 272 , 319 ]. They undergo rapid transformation to viscoelastic gels upon injection, prolonging their residence time and sustaining drug release, which will allow for less frequent dosing with enhanced bioavailability and lowered systemic absorption [ 320 ]. For intravitreal delivery, they also offer benefits of being transparent and clear (important for unhindered vision), and the ability to protect the incorporated drug from degradation in the vitreous [ 321 ].…”

Section: Polypeptide Deliverymentioning

confidence: 99%

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

et al. 2020

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Proteins and peptides have emerged in recent years to treat a wide range of multifaceted diseases such as cancer, diabetes and inflammation. The emergence of polypeptides has yielded advancements in the fields of biopharmaceutical production and formulation. Polypeptides often display poor pharmacokinetics, limited permeability across biological barriers, suboptimal biodistribution, and some proclivity for immunogenicity. Frequent administration of polypeptides is generally required to maintain adequate therapeutic levels, which can limit efficacy and compliance while increasing adverse reactions. Many strategies to increase the duration of action of therapeutic polypeptides have been described with many clinical products having been developed. This review describes approaches to optimise polypeptide delivery organised by the commonly used routes of administration. Future innovations in formulation may hold the key to the continued successful development of proteins and peptides with optimal clinical properties.

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“…To overcome the gel sterilization, the use of in situ stimuli-responsive gelling in response to environmental change (trigger), such as temperature triggered, ionic concentration, enzymes or pH lacrimal, has been proposed. For this gelling system, the sterilization of the dosage form would be in a value below that of the low critical system temperature, based on conformational changes in the polymer structure by weak acid or basic groups that accept protons in responsive changes (pH triggered), and by click reaction for ionotropic crosslinking that takes place due to single or double replacement reactions [ 63 , 64 ].…”

Section: Sterilization Of Ophthalmic Nanopharmaceuticalsmentioning

confidence: 99%

Nanopharmaceuticals for Eye Administration: Sterilization, Depyrogenation and Clinical Applications

Zielińska

Soles

Lopes

et al. 2020

Biology

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As an immune-privileged target organ, the eyes have important superficial and internal barriers, protecting them from physical and chemical damage from exogenous and/or endogenous origins that would cause injury to visual acuity or even vision loss. These anatomic, physiological and histologic barriers are thus a challenge for drug access and entry into the eye. Novel therapeutic concepts are highly desirable for eye treatment. The design of an efficient ocular drug delivery system still remains a challenge. Although nanotechnology may offer the ability to detect and treat eye diseases, successful treatment approaches are still in demand. The growing interest in nanopharmaceuticals offers the opportunity to improve ophthalmic treatments. Besides their size, which needs to be critically monitored, nanopharmaceuticals for ophthalmic applications have to be produced under sterilized conditions. In this work, we have revised the different sterilization and depyrogenation methods for ophthalmic nanopharmaceuticals with their merits and drawbacks. The paper also describes clinical sterilization of drugs and the outcomes of inappropriate practices, while recent applications of nanopharmaceuticals for ocular drug delivery are also addressed.

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Research progress of in-situ gelling ophthalmic drug delivery system

Cited by 196 publications

References 79 publications

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

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

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

Nanopharmaceuticals for Eye Administration: Sterilization, Depyrogenation and Clinical Applications

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