Topical Ocular Drug Delivery to the Back of the Eye by Mucus-Penetrating Particles

Schopf, Lisa; Попов, А. М.; Enlow, Elizabeth M.; Bourassa, James; Ong, Winston; Nowak, Paweł; Chen, Hongming

doi:10.1167/tvst.4.3.11

Cited by 63 publications

(78 citation statements)

References 44 publications

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“…They attributed this decrease to the reduction of mucoadhesive forces between the PLA-PEG NPs and the surface of the eye [174]. However, other more recent work by Schopf and coworkers suggested that nanoparticles coated with a dense, mucoinert PEG surface coating provided increased loteprednol etabonate (LE) delivery to the cornea and retina when applied topically to the surface of the rabbit eye compared to nanoparticles without a mucoinert PEG surface coating [176]. However, the mucoinert surface coating only led to improved LE delivery for nanoparticles (240 nm) and not microparticles (> 1 µm), suggesting that the nanoparticles (LE-MPP) were able to penetrate into the membrane-bound mucus layer of the eye, providing increased residence time and improved drug delivery.…”

Section: Non-systemic Applications For Improved Delivery With Pegymentioning

confidence: 99%

PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

Suk

Kim

et al. 2016

Advanced Drug Delivery Reviews

3,026

2,076

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Coating the surface of nanoparticles with polyethylene glycol (PEG), or “PEGylation”, is a commonly used approach for improving the efficiency of drug and gene delivery to target cells and tissues. Building from the success of PEGylating proteins to improve systemic circulation time and decrease immunogenicity, the impact of PEG coatings on the fate of systemically administered nanoparticle formulations has, and continues to be, widely studied. PEG coatings on nanoparticles shield the surface from aggregation, opsonization, and phagocytosis, prolonging systemic circulation time. Here, we briefly describe the history of the development of PEGylated nanoparticle formulations for systemic administration, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time. A less frequently discussed topic, we then describe how PEG coatings on nanoparticles have also been utilized for overcoming various biological barriers to efficient drug and gene delivery associated with other modes of administration, ranging from gastrointestinal to ocular. Finally, we describe both methods for PEGylating nanoparticles and methods for characterizing PEG surface density, a key factor in the effectiveness of the PEG surface coating for improving drug and gene delivery.

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Section: Non-systemic Applications For Improved Delivery With Pegymentioning

confidence: 99%

PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

Suk

Kim

et al. 2016

Advanced Drug Delivery Reviews

3,026

2,076

View full text Add to dashboard Cite

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“…[42,43] In particular, topical administration is inefficient in delivering medications to the posterior segment because of the rapid drainage through the nasolacrimal ducts, [44] as discussed in section 2.1.1. To reach the posterior segment of the eye, a topically administered drug must penetrate through the cornea (Figure 1), which represents a barrier from external agents that naturally serves to hinder the transport of either exogenous substances from the pre-corneal pockets.…”

Section: Routes Of Ocular Administrationmentioning

confidence: 99%

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Ratay

Bellotti

Gottardi³

et al. 2017

Adv Healthcare Materials

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Dry eye disease (DED), age-related macular degeneration (AMD), and Uveitis are ocular diseases that significantly affect the quality of life of millions of people each year. In these diseases, the action of chemokines, pro-inflammatory cytokines, and immune cells drives a local inflammatory response that results in ocular tissue damage. Multiple therapeutic strategies have been developed to either address the symptoms or abate the underlying cause of these diseases. Herein, we will review the challenges to deliver drugs to the relevant location in the eye for each of these diseases as well as current and innovative therapeutic approaches that attempt to restore homeostasis within the ocular microenvironment.

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“…Delivery of drugs to the posterior segment of the eye through oral/parenteral routes is highly challenging because of the expression of blood ocular barriers. Topical administration is promising in terms of safety and patient compliance but the delivery of therapeutic agents to the posterior ocular tissues through this route is also an extremely difficult task (3, 4). Although various technological advances enhanced drug delivery into the front-of-the eye, back-of-the eye delivery through the topical route needs innovative strategies to improve pre-corneal residence and trans-ocular permeation characteristics of drug molecules (5, 6).…”

Section: Introductionmentioning

confidence: 99%

Melt-Cast Noninvasive Ocular Inserts for Posterior Segment Drug Delivery

Balguri

Adelli

Tatke

et al. 2017

Journal of Pharmaceutical Sciences

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The objective of the present study is to evaluate the utility of melt-cast, topical, ocular inserts for delivery of drugs with different physicochemical properties. The model drugs tested include indomethacin (IN), ciprofloxacin Hydrochloride (CIP) and prednisolone sodium phosphate (PSP). Melt-cast method was used to fabricate ophthalmic inserts. Poly (ethylene oxide) N10, a semi-crystalline thermoplastic polymer (PE0 N10; Mol.wt: 100 kDa) was used as the matrix forming material. Polymeric insert units (4 × 2 × 0.2 mm) with a 10% w/w drug load were tested for in vitro release, transmembrane permeability and in vivo ocular tissue distribution. Marketed ophthalmic solutions were used as control solutions. Drug content in all the formulations ranged between 93 –102% of the theoretical value. Transmembrane flux of IN, PSP and CIP were enhanced by ~3.5-folds, ~3.6-folds and ~2.9-folds, respectively, from the polymeric inserts when compared to the control formulations, post 3 h. Moreover, ocular inserts generated significantly higher drug levels in all the ocular tissues, including the retina-choroid, when compared to their control formulations. The melt-cast ophthalmic inserts show promise as an effective noninvasive ocular drug delivery platform, which will be highly beneficial in the intervention and treatment of a wide variety of ocular complications.

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Topical Ocular Drug Delivery to the Back of the Eye by Mucus-Penetrating Particles

Abstract: These preclinical data support using MPP technology to engineer topical formulations to deliver therapeutic drug levels to the back of the eye and could provide major advancements in managing sight-threatening diseases.

Cited by 63 publications

References 44 publications

PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Melt-Cast Noninvasive Ocular Inserts for Posterior Segment Drug Delivery

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