Lisinopril in the composition of calcium phosphate nanoparticles as a promising antiglaucoma agent

A method of preparing calcium phosphate particles containing the angiotensin-converting enzyme inhibitor lisinopril has been suggested. The influence of the conditions of preparation of the particles on their characteristics (size, ζ-potential values, and structure) has been determined. It has been demonstrated that, at a reduced temperature (4°C) of preparation, particles with hydrodynamic radii 40–100 nm with a hollow porous structure and high degree of crystallinity are formed, while at high temperatures (40°C), amorphous particles with hydrodynamic radii 60–230 nm are formed. A decrease of the pH value of a medium from 7.5 to 5.8 resulted in the appearance of only large particles with mean hydrodynamic radius of approximately 400 nm. Replacing the potential-determining Na+ ions with K+ resulted in a higher absolute value of the ζ potential (−15 ± 2 mV compared to −6 ± 1 mV). It has been demonstrated in the experiments in vivo that lisinopril incorporated in the calcium phosphate particles caused a significantly stronger (approximately 2 times) and prolonged decrease of the intraocular pressure when compared to the same inhibitor used in the form of an aqueous solution.