Chitosan-covered calcium phosphate particles as a drug vehicle for delivery to the eye

Chitosan-Covered Calcium Phosphate Particles Co-Loaded with Superoxide Dismutase 1 and ACE Inhibitor: Development, Characterization and Effect on Intraocular Pressure

“…SOD1-loaded CaP-particles were obtained using slightly modified co-synthesis method [ 17 , 19 , 43 ]. All the solutions necessary for the synthesis ((12.5 mM K 2 HPO 4 containing 0.66 mg/mL (62.3 kU/mL) SOD1; 15.6–46.8 mM sodium citrate; 12.5 mM CaCl 2 )) were prepared and pre-filtered.…”

“…Covering CaP-particles with chitosan was performed as described in [ 19 ]. Briefly, 1 volume of 1 mg/mL 5 kDa chitosan in deionized water, pH 3.9, was added dropwise to 2 volumes of CaP-particle suspension, pH 6.5, with constant vigorous stirring on a magnetic stirrer (400 rpm).…”

“…The synthesis of CaP-nanoparticles is rather simple and inexpensive [ 13 ], and these particles are capable of incorporating both high and low-molecular-weight compounds [ 14 , 15 , 16 , 17 ]. We have previously demonstrated that the inclusion of low molecular weight drugs, β-adrenoblocker timolol [ 16 ], and the inhibitors of angiotensin-converting enzyme (ACE), into CaP-nanoparticles increased the effects of these drugs on the intraocular pressure (IOP) [ 17 , 18 , 19 ], while the inclusion of the antioxidant enzyme, superoxide dismutase 1 (SOD1), into such particles was shown to be effective in the treatment of oxidative stress and inflammation in immunogenic uveitis [ 20 ].…”

“…However, CaP-particles possess a negative surface charge [ 16 , 17 ], which might impair drug penetration into the eye due to the negatively charged mucin layer on the anterior eye surface [ 21 , 22 ]. Thus, the coating of CaP-particles with common positively charged mucoadhesive biopolymer chitosan [ 23 , 24 ] can enhance the affinity for the eye surface and increase the bioavailability of the included drug [ 18 , 19 ] without toxicity risks [ 25 ]. We have shown previously that hybrid chitosan-covered CaP-particles containing the ACE inhibitor, enalaprilat, demonstrated elevated retention time in the tear fluid and enhanced efficacy in lowering IOP with prolonged effect compared to both enalaprilat in solution and enalaprilat within uncovered CaP-particles [ 19 ].…”

Recent Progress in Chitosan-Based Nanomedicine for Its Ocular Application in Glaucoma

“…The developed enalaprilat nanoparticulate system had a much greater influence on IOP. This effect could be due to the higher zeta potential of glycol–chitosan coated calcium phosphate nanoparticles, which impart a greater affinity towards negatively charged ocular corneal cells and hence provide better penetration [ 81 ]. Recently, Rubennicia et al investigated the IOP lowering effect of latanoprost containing the chitosan–hyaluronic acid hybrid system in albino rats and compared its effect to the latanoprost alone [ 66 ].…”