Sustained delivery of anti-VEGFs from thermogel depots inhibits angiogenesis without the need for multiple injections

Ke-min, Xue; Zhao, Xinxin; Zhang, Zhongxing; Qiu, Beiying; Tan, Queenie Shu Woon; Ong, Kok Haur; Liu, Zengping; Parikh, Bhav Harshad; Barathi, Veluchamy A; Yu, Weimiao; Wang, Xiaomeng; Gopal, Lingam; Hunziker, Walter; Su, Xinyi; Loh, Xian Jun

doi:10.1039/c9bm01049a

Cited by 61 publications

(70 citation statements)

References 66 publications

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“…To date, non-biodegradable implants, nano-formulations and hydrogels have emerged as promising strategies (Fig. 2) [45]. Hydrogels have been used as promising materials for a variety of ophthalmic applications [46][47][48][49][50][51][52][53].…”

Section: Novel Sustained Drug Delivery Systems For Anti-vegf Agentsmentioning

confidence: 99%

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Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Seah

Zhao

Lin

et al. 2020

Eye

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Anti-vascular endothelial growth factors (anti-VEGF) have become the most common treatment modality for many retinal diseases. These include neovascular age-related macular degeneration (n-AMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusions (RVO). However, these drugs are administered via intravitreal injections that are associated with sight-threatening complications. The most feared of these complications is endophthalmitis, a severe infection of the eye with extremely poor visual outcomes. Patients with retinal diseases typically have to undergo multiple injections before achieving the desired therapeutic effect. Each injection incurs the risk of the sight-threatening complications. As such, there has been great interest in developing sustained delivery platforms for anti-VEGF agents to the posterior segment of the eye. In recent years, there have been various strategies that have been conceptualised. These include non-biodegradable implants, nano-formulations and hydrogels. In this review, the barriers of drug delivery to the posterior segment of the eye will be explained. The characteristics of an ideal sustained delivery platform will then be discussed. Finally, the current available strategies will be analysed with the above-mentioned characteristics in mind to determine the advantages and disadvantages of each sustained drug delivery modality. Through the above, this review attempts to provide an overview of the sustained delivery platforms in their various phases of development.These authors contributed equally: Ivan Seah Yu Jun, Zhao Xin Xin 1234567890();,:1234567890();,:

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Section: Novel Sustained Drug Delivery Systems For Anti-vegf Agentsmentioning

confidence: 99%

“…Most hydrogel platforms have not only shown to be biocompatible but also allow a sustained release of bioactive anti-VEGF to the retina for durations of multiple months [91,92,[98][99][100][101][102] (Table 2). Yu et al developed a hydrogel system comprised of natural polymers.…”

Section: Hydrogels For Sustained Delivery Of Anti-vegfmentioning

confidence: 99%

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Seah

Zhao

Lin

et al. 2020

Eye

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“…The anti-VEGFs showed activity for up to 40 days, with antiangiogenic effects depicted both ex vivo and in vivo. This study is a steppingstone for the development and use of thermogels in the delivery of bioactive protein molecules (Xue et al, 2019). In another study, gel strength drug release profiles were improved by combining PEG-PCL-PEG, pluronic F127, and poly propylene fumarate (PPF) in a ratio of 4:1:1 in the formulation of an innovative successful pseudo-bone thermogel.…”

Section: Pcl-peg Based Thermogelsmentioning

confidence: 98%

“…Upon heating, the multiblock copolymer is able to generate crosslinks and form a hydrogel under mild conditions to encapsulate protein drug. Reproduced with permission from Royal Society of Chemistry,Xue et al (2019).…”

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confidence: 99%

Hybrid Thermo-Responsive Polymer Systems and Their Biomedical Applications

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Targeted and controlled drug delivery employing "smart materials" is a widely investigated field, within which stimuli-responsive polymers, particularly those which are thermo-responsive, have received considerable attention. Thermo-responsive polymers have facilitated the formulation of in situ gel forming systems which undergo a sol-gel transition at physiological body temperature, and have revolutionized the fields of tissue engineering, cell encapsulation, and controlled, sustained delivery of both drugs and genes. However, the use of single thermo-responsive polymers in the creation of these systems has posed numerous problems in terms of physico-mechanical properties, such as poor mechanical strength, high critical gelation concentrations (CGC) resulting in increased production costs and solutions that are too viscous, toxicity, as well as gelation temperatures that are incompatible with physiological body temperatures. Hybridization of these thermo-responsive polymers with other polymers has therefore been employed, resulting in the creation of tailor-made drug delivery systems that have optimal gelation temperatures and concentrations, ideal viscosities and improved gel strengths. This article reviews various thermo-responsive polymers that have been employed in the formulation of thermo-gelling systems. Special attention has been given to the hybridization of each of these polymers, the resulting systems that have been created, and their biomedical applications.

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“…They are also useful for circumventing the need for frequent repeat injections—which presents several risks and complications to patients—by acting as a drug depot even for unstable protein molecules [ 140 ]. There are a number of in-situ gelling systems reported for ocular delivery of proteins [ 225 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 , 308 ]. Xue et al [ 305 ] developed thermosensitive gels of anti-VEGF drugs (bevacizumab and aflibercept) using a PEG-polypropylene glycol (PPG)-PCL multiblock copolymer (hydrophilic–hydrophobic biodegradable copolymer) [ 305 ].…”

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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Sustained delivery of anti-VEGFs from thermogel depots inhibits angiogenesis without the need for multiple injections

Abstract: Polyurethane thermogels show sustained delivery of bioactive anti-VEGFs therapeutics to the eye.

Cited by 61 publications

References 66 publications

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Hybrid Thermo-Responsive Polymer Systems and Their Biomedical Applications

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

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