Nanomedicine for Improved Ocular Drug Delivery

  • Type:
    Conference Presentation
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    AIChE Member Credits 0.5
    AIChE Members $19.00
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    AIChE Undergraduate Student Members Free
    Non-Members $29.00
  • Conference Type:
    AIChE Annual Meeting
  • Presentation Date:
    November 9, 2021
  • Duration:
    50 minutes
  • Skill Level:
    Intermediate
  • PDHs:
    0.50

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Eye drops are the dominant dosage form for the ocular route, and are used for a wide range of indications, including glaucoma, dry eye, inflammation, infection and allergy. However, as with all exposed epithelial surfaces, there are innate protective mechanisms that hinder efficient drug delivery to the eye. Thus, only a small fraction of drugs administered by eye drops is typically absorbed into the eye, often necessitating multiple doses per day. As the number of eye drop doses per day increases, so does the potential for ocular surface irritation and systemic side effects, while patient compliance to the treatment regimen decreases. To address these issues, we have developed hypotonic gelling formulations that provide enhanced topical ocular drug delivery for a range of drugs for different ocular indications affecting both the anterior and posterior segment. We demonstrate that our hypotonic, lower concentration thermogelling formulations outperform both conventional isotonic thermogelling formulations and commercial eye drops for drugs that lower intraocular pressure, both hydrophilic (brimonidine tartrate) and hydrophobic (brinzolamide), as well as a hydrophobic peptide drug (cyclosporine) used for treating dry eye. Importantly, our hypotonic gelling formulation caused no signs of ocular irritation or toxicity with twice-daily administration for up to five weeks in rabbits, as measured by corneal staining, blink-rate test and corneal histology. Further, characterization of the uniformity, refractive index and absorbance suggest that visual clarity is maintained and the shear-thinning properties are similar to those of commercial lubricating eye drops. We also provide data to support the hypothesis that by holding the drug at high concentration at the ocular surface, drug delivery to the posterior retina and choroid can be increased. We demonstrate proof-of-principle with topically delivering drugs that inhibit hypoxia inducible factor 1 (acriflavine) and vascular endothelial growth factor receptor (sunitinib) to prevent laser-induced choroidal neovascularization in mice. Importantly, therapeutic drug delivery to the posterior segment was confirmed in large animals with eyes similar in size to the human eye, also providing protection against prevention of laser-induced choroidal neovascularization. Our findings highlight the importance of formulations that conform to the ocular surface before viscosity enhancement for increased and prolonged ocular surface contact and drug absorption. The therapeutic implications span a variety of ocular indications with the potential for enhanced disease management and patient quality of life.
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Pricing


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AIChE Member Credits 0.5
AIChE Members $19.00
AIChE Graduate Student Members Free
AIChE Undergraduate Student Members Free
Non-Members $29.00
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