Because of their high specificity and low side effects,
protein drugs possess a substantial global market. However, the low bioavailability of
protein is still a major obstacle to their expanded applications, which is expected to be answered with proper
protein formulations. Taking
corneal neovascularization (CNV) as an example, we demonstrated a co-assembled system of hexa-
histidine and Ava (
Avastin) with
metal ions (HmA@Ava) could cross the cornea, the most important bio-barrier during the treatment of most diseases of the anterior segment in clinics. We found that the nanosized HmA@Ava efficiently encapsulated Ava with impressive loading capacity without destroying the bioactivity of Ava and assisted Ava penetration through the corneal barriers to effectively inhibit CNV development in an
alkali burn rat model with sustained and pH-dependent Ava release. Our results suggested that the co-assembled strategy of
protein and HmA is a proper formulation to
protein drugs, with promising penetration ability to deliver
protein across bio-barriers, which could open a path for
topical administration of
protein drugs for treatment of various ocular diseases and hold enormous potential for delivery of therapeutic
proteins not only for ocular diseases but also for other diseases that require
protein treatment.