Design principles of ocular drug delivery systems: importance of drug payload, release rate, and material properties

Subrizi, Astrid; Amo, Eva M. del; Korzhikov-Vlakh, Viktor; Tennikova, Tatiana; Ruponen, Marika; Urtti, Arto

doi:10.1016/j.drudis.2019.02.001

Cited by 159 publications

(125 citation statements)

References 107 publications

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“…The nature of the drug being delivered, the polymer additive, its concentration, and the use of preservative can be adapted to create the best possible combination of properties for the desired treatment effect. These changes only have minimal impact on the objectively low efficacy of eye drops compared to more invasive treatments (e.g., such as intraocular injections) for certain diseases 2. Despite this, eye drops still offer an attractive treatment option, due to their ease of administration, versatility, and low cost.…”

Section: Topical Ocular Drug Delivery: Eye Dropsmentioning

confidence: 99%

“…Another innovation investigated for overcoming the eye's natural barriers to drug delivery and improving the bioavailability of the carried drug is to increase the viscosity of the eye drop 7a,69b,82. Tests have shown that more viscous drops show a higher resistance to lacrimal clearance and stay resident on the surface of the eye longer 2,10b,38,51,61,76,83. As with mucoadhesion, this increases the window available for drug delivery.…”

Section: Innovations In Topical Ocular Drug Deliverymentioning

confidence: 99%

“…The mechanism of drug loading is also important, as different methods create different release profiles but also involve different solvents 92. The loading of nanoparticles is also limited by the fact that the encapsulated phase makes up a very small fraction of the overall mixture, and the loading is limited to the equilibrium point between the phases 93. Encapsulated delivery systems also pose the risk of premature release in storage which can decrease the possible dosage in vivo.…”

Section: Innovations In Topical Ocular Drug Deliverymentioning

confidence: 99%

“…It is well documented that biological systems that keep the eye free of debris and pathogens and protect the vital posterior structures, present a barrier to topical drug delivery 1. Usual treatments for ocular diseases include intraocular injections, surgical interventions, and/or eye drops 2. Eye drops are most commonly used for treating conditions affecting the anterior structures of the eye ( Figure )—the cornea, conjunctiva, sclera, and trabecular meshwork—as passage through these structures to the posterior segment of the eye is relatively restricted 3.…”

Section: Introduction: the Barriers To Topical Ocular Drug Deliverymentioning

confidence: 99%

“…[1] Usual treatments for ocular diseases include intraocular injections, surgical interventions, and/or eye drops. [2] Eye drops are most commonly used for treating conditions affecting the anterior structures of the eye (Figure 1)-the cornea, conjunctiva, sclera, and trabecular meshwork-as passage through these structures to the posterior segment of the eye is relatively restricted. [3] The cornea comprises sublayers with different properties; the epithelial and endothelial layers are lipophilic, and the stroma is hydrophilic.…”

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confidence: 99%

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Material, Immunological, and Practical Perspectives on Eye Drop Formulation

Bennett

Chinnery

Downie

et al. 2020

Adv Funct Materials

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Eye drops are the most common and inexpensive approach to topical ocular drug delivery. Eye drops offer a noninvasive treatment strategy; however, this can be detrimental to therapeutic efficacy when compared to invasive methods such as surgeries, implants, and injections. Improvements to the efficacy of the topical delivery of drugs to ocular tissues are currently being explored and much of this work centers on adjusting the formulation of the eye drops and prolonging the bioavailability of the therapeutic agent. This is often in preference to improving other patient‐focused or clinical factors. In this progress report, conventional, commercially available polymer eye drops are explored and the ability for current and future innovations to maintain the existing benefits of eye drops to the patient is assessed. The final materials and form of the drops (liquid, gel, or other) and the immunological implications for the user are explored. There is currently no consensus for how to most effectively improve the ocular retention and drug delivery capabilities of eye drops, but key issues are highlighted in the context of current methods under development, and potential questions and considerations for future innovations are raised.

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Section: Topical Ocular Drug Delivery: Eye Dropsmentioning

confidence: 99%

Section: Innovations In Topical Ocular Drug Deliverymentioning

confidence: 99%

Section: Innovations In Topical Ocular Drug Deliverymentioning

confidence: 99%

Section: Introduction: the Barriers To Topical Ocular Drug Deliverymentioning

confidence: 99%

mentioning

confidence: 99%

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Material, Immunological, and Practical Perspectives on Eye Drop Formulation

Bennett

Chinnery

Downie

et al. 2020

Adv Funct Materials

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The Design and Developments of Protein‐Polysaccharide Biomaterials for Corneal Tissue Engineering

Prasathkumar

Chenthamara

Lin

et al. 2023

Adv Materials Technologies

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Corneal blindness is explained by a large reduction in vision loss caused by acute and chronic corneal diseases and/or disorders. Due to the severe unavailability of donor corneas, immune rejection, and the side effects of keratoprosthesis (KPro), vision‐impaired patients are often unable to restore their vision. Corneal tissue engineering appears to be a promising method using natural polymers made from different layers of corneal cells such as epithelium, stroma, and endothelium or full tissue equivalents. Proteins and polysaccharides are able to mimic the chemical composition of the native extracellular matrix (ECM), which has been extensively studied for corneal tissue engineering. Additionally, protein‐based materials are highly favored in corneal regenerative therapy as they have the proper cell‐binding sites for cell adhesion, corneal innervation regeneration, and oxidative stress suppression, while polysaccharide‐based materials can also promote cell proliferation and adhesion as well as ocular permeability. Herein, a comprehensive review of various biomaterials based on natural proteins (fibrin, fibrinogen, silk fibroin, collagen, gelatin, and serum albumin) and polysaccharides (chitin, chitosan, hyaluronic acid, alginate, cellulose, and gellan gum) for corneal tissue engineering are provided. The protein‐polysaccharide biomaterials are mainly used in the form of hydrogels, films, scaffolds, sutures, eye drops, nanocarriers, and nanocapsules to treat ocular diseases that cause blindness, such as corneal wounds, corneal ulcers, Goldenhar syndrome, corneal endothelium and stroma defects, corneal neovascularization, etc. In this review, insight is provided into recent developments in the areas of biomaterial design, cross‐linking strategy, corneal cell selection, and frontiers that are expected to offer researchers support and creativity in the development of corneal regenerative medicine.

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HDL Nanoparticles Have Wound Healing and Anti‐Inflammatory Properties and Can Topically Deliver miRNAs

Wang

Calvert

Kaplan

et al. 2020

Advanced Therapeutics

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microRNAs regulate numerous biological processes, making them potential therapeutic agents. Problems with delivery and stability of these molecules have limited their usefulness as treatments. It is demonstrated that synthetic high-density lipoprotein nanoparticles (HDL NPs) topically applied to the intact ocular surface are taken up by epithelial and stromal cells. microRNAs complexed to HDL NPs (miR-HDL NPs) are similarly taken up by cells and tissues and retain biological activity. Topical treatment of diabetic mice with either HDL NPs or miR-HDL NPs significantly improves corneal reepithelialization following wounding compared with controls. Mouse corneas with alkali burn-induced inflammation, topically treated with HDL NPs, display clinical, morphological, and immunological improvement. These results yield a novel HDL NP-based eye drop for patients with compromised wound healing ability (diabetics) and/or corneal inflammatory diseases (e.g., dry eye).

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Design principles of ocular drug delivery systems: importance of drug payload, release rate, and material properties

Cited by 159 publications

References 107 publications

Material, Immunological, and Practical Perspectives on Eye Drop Formulation

Material, Immunological, and Practical Perspectives on Eye Drop Formulation

The Design and Developments of Protein‐Polysaccharide Biomaterials for Corneal Tissue Engineering

HDL Nanoparticles Have Wound Healing and Anti‐Inflammatory Properties and Can Topically Deliver miRNAs

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