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WIREs Nanomed Nanobiotechnol
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Controlled ocular drug delivery with nanomicelles

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Many vision threatening ocular diseases such as age‐related macular degeneration (AMD), diabetic retinopathy, glaucoma, and proliferative vitreoretinopathy may result in blindness. Ocular drug delivery specifically to the intraocular tissues remains a challenging task due to the presence of various physiological barriers. Nonetheless, recent advancements in the field of nanomicelle‐based novel drug delivery system could fulfil these unmet needs. Nanomicelles consists of amphiphilic molecules that self‐assemble in aqueous media to form organized supramolecular structures. Micelles can be prepared in various sizes (10–1000 nm) and shapes depending on the molecular weights of the core and corona forming blocks. Nanomicelles have been an attractive carrier for their potential to solubilize hydrophobic molecules in aqueous solution. In addition, small size in nanometer range and highly modifiable surface properties have been reported to be advantageous in ocular drug delivery. In this review, various factors influencing rationale design of nanomicelles formulation and disposition are discussed along with case studies. Despite the progress in the field, influence of various properties of nanomicelles such as size, shape, surface charge, rigidity of structure on ocular disposition need to be studied in further details to develop an efficient nanocarrier system. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies
The anatomy of the eye and various routes of administrations. Credit: National Eye Institute, National Institutes of Health.
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Schematic illustration of formation of polyionic complex (PIC) micelles.
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Dexamethasone concentrations in aqueous humor after administration to rabbits. Circles are PHEA‐PEG‐C16 micelles and squares are dexamethasone suspension. Each data point corresponds to the mean dexamethasone concentration in ng/mL ± SEM determinated in the aqueous humor at each sample time. *Student's t‐test, P < 0.05. (Reproduced with permission Ref )
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Cumulative amounts of DEX released from human sclera in the release studies performed after the passive (open diamonds) and cathodal iontophoretic (closed diamonds) transport experiments of UMM. The results of the control after passive delivery (open triangles) are presented again for comparison. Data represent the mean and standard deviation, n ≥ 3. (Reproduced with permission Ref )
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Release profile of DEX from the F127 and F127/chitosan micelle systems under sink conditions at 25°C (mean ± SD, n = 3). (Reproduced with permission from Ref . Copyright xxxx)
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Structures of various micelle forming amphiphilic polymers and surfactants. Corona forming hydrophilic part of amphiphilic molecule is shown as blue color.
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Schematic illustration of formation of spherical micelle and drug encapsulation. Above critical micelle concentration the amphiphilic molecule (Surfactant or polymer) self‐assemble to form core‐shell structure depicted above. Hydrophobic drug (black dots) may be encapsulated during or after the micelle formation. The hydrophilic segment (Blue color) could be water soluble polymer like poly(ethylene glycol) (PEG) or charged group of surfactant. Hydrophobic segment (Gray color) could be water insoluble lipid or polymer chain.
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