Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses.

PURPOSE: The majority of contact lens wearers experience a significant level of ocular discomfort associated with lens wear, often within hours of wear, related to dry lenses, inflammation, protein adhesion to the lens surface, etc. Application of controlled drug release techniques has focused on the incorporation and/or release of a single comfort molecule from a lens including high molecular weight comfort agents or pharmaceutical agents. Previous studies have sought to mitigate the occurrence of only single propagators of discomfort. Clinical studies with eye drop solutions have shown that a mixture of diverse comfort agents selected to address multiple propagators of discomfort provide the greatest and longest lasting sensations of comfort for the patient. In this paper, multiple propagators of discomfort are addressed through the simultaneous release of four molecules from a novel contact lens to ensure high level of lens wear comfort. METHODS: Silicone hydrogel contact lenses were engineered via molecular imprinting strategies to simultaneously release up to four template molecules including hydropropyl methylcellulose (HPMC), trehalose, ibuprofen, and prednisolone. RESULTS: By adjusting the ratio of functional monomer to comfort molecule, a high level of control was demonstrated over the release rate. HPMC, trehalose, ibuprofen, and prednisolone were released at therapeutically relevant concentrations with varying rates from a single lens. CONCLUSIONS: The results indicate use as daily disposable lenses for single day release or extended-wear lenses with multiple day release. Imprinted lenses are expected to lead to higher efficacy for patients compared to topical eye drops by improving compliance and mitigating concentration peaks and valleys associated with multiple drops.

Nucleic acid biohybrid nanocarriers with high-therapeutic payload and controllable extended release of daunomycin for cancer therapy.

We have developed a novel, nanosized drug carrier with high-therapeutic payload, controllable release, and the potential for active tumor targeting. It consists of a 15 nm gold nanoparticle with dense surface loading of DNA duplexes. We utilize the natural intercalating behavior of daunomycin to load the drug between DNA base pairs. We obtained a high-therapeutic payload of >1,000 drug molecules per gold nanoparticle (AuNP), one of the highest loadings reported in literature to date. We have engineered unique DNA sequences to control release of daunomycin for over 48 hr and show higher cell death compared to equivalent concentrations of free daunomycin. We have also explored cell internalization mechanisms to identify the pathways by which our gold nanoparticles enter the cell. This nanocarrier is in the ideal size range of 16-100 nm in diameter to utilize the enhanced permeability and retention effect for passive targeting to tumors. Our AuNP platform is effective as a therapeutic drug delivery device and can easily incorporate any aptamer of choice through complementary base pairing. Our work has produced an innovative nanoscale drug-delivery platform potentially leading to personalized cancer therapies through careful selection of aptamers and an adjustable drug release profile.

Challenges and solutions in topical ocular drug-delivery systems.

Vision significantly affects quality of life and the treatment of ocular disease poses a number of unique challenges. This review presents the major challenges faced during topical ocular drug administration and highlights strategies used to overcome the natural transport barriers of the eye. The circulation of tear fluid and aqueous humor decrease the residence time of topically delivered drugs, while ocular barriers in the corneal and conjuctival epithelia and the retinal pigment epithelium limit transport. Successful treatment strategies increase the residence time of drugs in the eye and/or enhance the ability of the drug to penetrate the ocular barriers and reach the target tissue. In this review, we discuss several drug-delivery strategies that have achieved clinical success or demonstrate high potential. We also draw attention to a number of excellent reviews that explore various ocular drug-delivery techniques in depth. Finally, we highlight cutting-edge drug-delivery technologies that improve the efficacy of current drug-delivery methods or use proven techniques to deliver novel therapeutics.