Commercialization challenges for drug eluting contact lenses.

INTRODUCTION: Eye drops are commonly used for delivering ophthalmic drugs despite many deficiencies including low bioavailability and poor compliance. Contact lenses can deliver drugs with high bioavailability but commercial contacts release drug rapidly, limiting benefits and necessitating modifications to improve the drug release characteristics. AREAS COVERED: This review covers the common approaches to prolong the release rates of drugs from contact lenses including molecular imprinting, incorporation of nano/microparticles, vitamin-E barriers, and layered/implant contact lenses. It also evaluates their suitability for commercialization and discusses challenges that need to be addressed before commercialization is possible. EXPERT OPINION: In spite of many benefits of contact lenses compared to eye drops, a drug-eluting contact lens has not emerged in the market due to many reasons including potential safety risks, patient and practitioner acceptance, and production and storage factors. Importantly, changes in the critical lens properties must also be considered such as ion and oxygen permeability, loss in modulus, optical and swelling properties, and protein adherence upon drug loading. Many technologies have addressed scientific and commercialization challenges and are currently being tested both in animal and clinical studies. It is likely that a drug-eluting contact lens will be commercialized in the future.

The nucleus is irreversibly shaped by motion of cell boundaries in cancer and non-cancer cells.

Actomyosin stress fibers impinge on the nucleus and can exert compressive forces on it. These compressive forces have been proposed to elongate nuclei in fibroblasts, and lead to abnormally shaped nuclei in cancer cells. In these models, the elongated or flattened nuclear shape is proposed to store elastic energy. However, we found that deformed shapes of nuclei are unchanged even after removal of the cell with micro-dissection, both for smooth, elongated nuclei in fibroblasts and abnormally shaped nuclei in breast cancer cells. The lack of shape relaxation implies that the nuclear shape in spread cells does not store any elastic energy, and the cellular stresses that deform the nucleus are dissipative, not static. During cell spreading, the deviation of the nucleus from a convex shape increased in MDA-MB-231 cancer cells, but decreased in MCF-10A cells. Tracking changes of nuclear and cellular shape on micropatterned substrata revealed that fibroblast nuclei deform only during deformations in cell shape and only in the direction of nearby moving cell boundaries. We propose that motion of cell boundaries exert a stress on the nucleus, which allows the nucleus to mimic cell shape. The lack of elastic energy in the nuclear shape suggests that nuclear shape changes in cells occur at constant surface area and volume.