Publications by authors named "Matthew B Appell"

Vaginal drug delivery is often preferred over systemic delivery to reduce side effects and increase efficacy in treating diseases and conditions of the female reproductive tract (FRT). Current vaginal products have drawbacks, including spontaneous ejection of drug-eluting rings and unpleasant discharge from vaginal creams. Here, we describe the development and characterization of a hypotonic, gel-forming, Pluronic-based delivery system for vaginal drug administration.

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Neurodegenerative diseases affecting the visual system encompass glaucoma, macular degeneration, retinopathies, and inherited genetic disorders such as retinitis pigmentosa. These ocular pathologies pose a serious burden of visual impairment and blindness worldwide. Current treatment modalities include small molecule drugs, biologics, or gene therapies, most of which are administered topically as eye drops or as injectables.

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Effective eye drop delivery systems for treating diseases of the posterior segment have yet to be clinically validated. Further, adherence to eye drop regimens is often problematic due to the difficulty and inconvenience of repetitive dosing. Here, we describe a strategy for topically dosing a peptide-drug conjugate to achieve effective and sustained therapeutic sunitinib concentrations to protect retinal ganglion cells (RGCs) in a rat model of optic nerve injury.

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Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye.

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There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenient for patients, and lack of adherence to prescribed dosing regimens limits treatment efficacy and contributes to antibiotic resistance.

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While eye drops are the most common ocular dosage form, eye drops for treating diseases of the posterior segment (retina, choroid, optic nerve) have yet to be developed. In glaucoma, eye drops are used extensively for delivering intraocular pressure (IOP)-lowering medications to the anterior segment. However, degeneration of retinal ganglion cells (RGCs) in the retina may progress despite significant IOP lowering, suggesting that a complementary neuroprotective therapy would improve glaucoma management.

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