Efficient delivery of instilled drugs into the corneal stroma and intraocular tissues remains a major challenge in ophthalmic pharmacology. Existing enhancers of transmucosal and transepithelial permeability are often toxic and fail to overcome ocular surface barriers effectively. Dynamic modulation of ocular surface acidity during drug instillation represents a promising approach for gentle “opening” of these barriers and enhancing the bioavailability of certain classes of drugs.

PURPOSE

This study aimed to develop a pharmaceutically acceptable eye drop vehicle based on an overloaded pH buffer capable of dynamically regulating ocular surface acidity and thereby ensuring effective and safe transmucosal and transepithelial delivery of substances.

MATERIAL AND METHODS

This pilot study included six rabbits (four groups). The permeability of copper (Cu²⁺) and neodymium (Nd³⁺) ions was investigated; these ions were selected as models due to their high affinity for mucins and the epithelium. The ions were delivered into the corneal stroma using a vehicle based on an overloaded pH buffer and phosphate-buffered saline (PBS). Stromal concentrations were assessed as follows: Cu — by atomic absorption spectrometry, Nd — by energy-dispersive spectrometry. The absence of toxic reactions was confirmed by biomicroscopy.

RESULTS

The eye drop vehicle based on an overloaded pH buffer increased the stromal copper concentration by 1.6-fold compared to PBS (0.54 vs 0.33 mg/kg). The new vehicle enabled significant accumulation of Nd in the corneal stroma at 0.39 wt% [0.36—0.43 wt.%], whereas with PBS the stromal Nd level was measured at 0.07 wt.% [0.07—0.08 wt.%] (below the detection threshold of p<0.001).

CONCLUSIONS

The eye drop vehicle based on an overloaded pH buffer provides a physiological and significant enhancement of transmucosal and transepithelial transport of cationic substances without inducing ocular tissue damage. This approach may increase drug bioavailability, reduce the required initial dose of active components in dosage forms, decrease toxic burden, and eliminate the need for toxic permeability enhancers in ophthalmic formulations.