Ocular therapies with biomacromolecules: From local injection to eyedrop and emerging noninvasive delivery strategies

The last two decades have witnessed a continuously increasing number of biomacromolecules approved for the treatment of ocular diseases. The eye possesses multiple protective mechanisms to resist the invasion of exogenous substances, but meanwhile these physiological defense systems also act as strong barriers, impeding absorption of most biomacromolecules into the eye. As a result, local injections play predominant roles for posterior ocular delivery of biomacromolecules in clinical practice. To achieve safe and convenient application of biomacromolecules, alternative strategies to realize noninvasive intraocular delivery are necessary. Various nanocarriers, novel penetration enhancers and physical strategies have been explored to facilitate delivery of biomacromolecules to both anterior and posterior ocular segments but still suffered difficulties in clinical translation. This review compares the anatomical and physiological characteristics of the eyes from those frequently adopted experimental species and profiles the well-established animal models of ocular diseases. We also summarize the ophthalmic biomacromolecules launched on the market and put emphasis on emerging noninvasive intraocular delivery strategies of peptides, proteins and genes.