Tunable release of ophthalmic therapeutics from injectable, resorbable, thermoresponsive copolymer scaffolds

Prosperi-Porta, Graeme; Muirhead, Benjamin; Sheardown, Heather

doi:10.1002/jbm.b.33501

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…Several labs are investigating additional polymer systems for intravitreal use. This includes our work developing polydopamine nanoparticles for anti-VEGF delivery, as well as efforts by other labs developing technologies such as phase-inversion mixtures of polymer and solvent, PEGylated siloxanes, and NIPAAmbased thermoresponsive polymers for intravitreal (130,229,230). Some of these systems are currently being translated for commercial use, such as ReVana Therapeutics' EyeLief TM and OcuLief TM injectable polymers (231).…”

Section: Intravitreal Injections and Implantsmentioning

confidence: 99%

Considerations for Polymers Used in Ocular Drug Delivery

et al. 2022

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PurposeAge-related eye diseases are becoming more prevalent. A notable increase has been seen in the most common causes including glaucoma, age-related macular degeneration (AMD), and cataract. Current clinical treatments vary from tissue replacement with polymers to topical eye drops and intravitreal injections. Research and development efforts have increased using polymers for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. Polymers provide unique properties that allow for specific engineered devices to provide improved treatment options. Recent work has shown the utilization of synthetic and biopolymer derived biomaterials in various forms, with this review containing a focus on polymers Food and Drug Administration (FDA) approved for ocular use.MethodsThis provides an overview of some prevalent synthetic polymers and biopolymers used in ocular delivery and their benefits, brief discussion of the various types and synthesis methods used, and administration techniques. Polymers approved by the FDA for different applications in the eye are listed and compared to new polymers being explored in the literature. This article summarizes research findings using polymers for ocular drug delivery from various stages: laboratory, preclinical studies, clinical trials, and currently approved. This review also focuses on some of the challenges to bringing these new innovations to the clinic, including limited selection of approved polymers.ResultsPolymers help improve drug delivery by increasing solubility, controlling pharmacokinetics, and extending release. Several polymer classes including synthetic, biopolymer, and combinations were discussed along with the benefits and challenges of each class. The ways both polymer synthesis and processing techniques can influence drug release in the eye were discussed.ConclusionThe use of biomaterials, specifically polymers, is a well-studied field for drug delivery, and polymers have been used as implants in the eye for over 75 years. Promising new ocular drug delivery systems are emerging using polymers an innovative option for treating ocular diseases because of their tunable properties. This review touches on important considerations and challenges of using polymers for sustained ocular drug delivery with the goal translating research to the clinic.

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Section: Intravitreal Injections and Implantsmentioning

confidence: 99%

Considerations for Polymers Used in Ocular Drug Delivery

et al. 2022

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“…These kinds of hydrogels exhibited fast and reversible phase changes with alteration in temperature, and their release profiles resulted as a function of the cross-link density [54,55]. In other research studies, copolymers based on acrylic acid N -hydroxysuccinimide (NAS), N -isopropylacrylamide (NIPAM) and increasing concentrations of acryloyloxy dimethyl-γ-butyrolactone (DBA) and acrylic acid (AA) were synthesized with the aim to obtain thermoresponsive, resorbable copolymers suitable to deliver drugs and/or cells to the posterior segment of the eye in a minimally invasive manner [56,57]. Copolymers of NIPAM and NAS were also conjugated with cell adhesive peptides and amine-functionalized hyaluronic acid.…”

Section: Thermosensitive Ddsmentioning

confidence: 99%

Ocular Drug Delivery: A Special Focus on the Thermosensitive Approach

et al. 2019

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The bioavailability of ophthalmic therapeutics is reduced because of the presence of physiological barriers whose primary function is to hinder the entry of exogenous agents, therefore also decreasing the bioavailability of locally administered drugs. Consequently, repeated ocular administrations are required. Hence, the development of drug delivery systems that ensure suitable drug concentration for prolonged times in different ocular tissues is certainly of great importance. This objective can be partially achieved using thermosensitive drug delivery systems that, owing to their ability of changing their state in response to temperature variations, from room to body temperature, may increase drug bioavailability. In the case of topical instillation, in situ forming gels increase pre-corneal drug residence time as a consequence of their enhanced adhesion to the corneal surface. Otherwise, in the case of intraocular and periocular, i.e., subconjunctival, retrobulbar, peribulbar administration, among others, they have the undoubted advantage of being easily injectable and, owing to their sudden thickening at body temperature, have the ability to form an in situ drug reservoir. As a result, the frequency of administration can be reduced, also favoring the patient’s adhesion to therapy. In the main section of this review, we discuss some of the most common treatment options for ocular diseases, with a special focus on posterior segment treatments, and summarize the most recent improvement deriving from thermosensitive drug delivery strategies. Aside from this, an additional section describes the most widespread in vitro models employed to evaluate the functionality of novel ophthalmic drug delivery systems.

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“…51 However, from a biomedical translational perspective in terms of bringing such nanogels to practical use as nanotherapeutics, the use of PNIPAM remains challenging. Although most cytocompatibility and tissue compatibility studies involving PNIPAM-based materials have yielded promising results, 51,54,55 the highly toxic nature of the NIPAM monomer and the lack of a clear degradation pathway for PNIPAM in vivo has complicated the regulatory approval of PNIPAM for biomedical use.…”

Section: Introductionmentioning

confidence: 99%

Narrowly Dispersed, Degradable, and Scalable Poly(oligoethylene glycol methacrylate)-Based Nanogels via Thermal Self-Assembly

Simpson

Corbett

Arezina

et al. 2018

Ind. Eng. Chem. Res.

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Covalently cross-linked and hydrolytically degradable poly(oligoethylene glycol methacrylate) (POEGMA)based nanogels are fabricated using an all-aqueous self-assembly approach. The nanogels are composed of hydrazide-(POH) and aldehyde-functionalized (POA) POEGMA precursor polymers that exhibit lower critical solution temperature (LCST) behavior in aqueous media and form a covalent, yet degradable, hydrazone linkage upon mixing. By systematically changing the chemistry of the core and cross-linking precursor polymers, the concentration of the core precursor polymer, the ratio of core to cross-linking precursor polymer, and the temperature at which the assembly is conducted, a library of nanogels was produced with significant differences in size, polydispersity, and colloidal stability. Multivariate statistics indicates the presence of significant nonlinear responses within the process variables as well as correlations between the output variables, reflective of the complex balance of aggregation and stabilization mechanisms at play to produce a stable, monodisperse nanogel population. Furthermore, formulations that yield more polydisperse nanogels on a small scale result in macroscopic aggregate formation when scaled up while formulations that yield more monodisperse nanogels can be scaled to yield nanogels with matched properties. We anticipate these results can be applied to strategically synthesize stable, covalently cross-linked, degradable nanogels with targeted sizes at scalable quantities for a range of biomedical and biosensing applications.

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Tunable release of ophthalmic therapeutics from injectable, resorbable, thermoresponsive copolymer scaffolds

Cited by 6 publications

References 39 publications

Considerations for Polymers Used in Ocular Drug Delivery

Considerations for Polymers Used in Ocular Drug Delivery

Ocular Drug Delivery: A Special Focus on the Thermosensitive Approach

Narrowly Dispersed, Degradable, and Scalable Poly(oligoethylene glycol methacrylate)-Based Nanogels via Thermal Self-Assembly

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