Ocular diseases can deteriorate vision to the point of blindness and thus can have a major impact on the daily life of an individual. Conventional therapies are unable to provide absolute therapy for all ocular diseases due to the several limitations during drug delivery across the blood-retinal barrier, making it a major clinical challenge. With recent developments, the vast number of publications undergird the need for nanotechnology-based drug delivery systems in treating ocular diseases. The tool of nanotechnology provides several essential advantages, including sustained drug release and specific tissue targeting. Additionally, comprehensive in vitro and in vivo studies have suggested a better uptake of nanoparticles across ocular barriers. Nanoparticles can overcome the blood-retinal barrier and consequently increase ocular penetration and improve the bioavailability of the drug. In this review, we aim to summarize the development of organic and inorganic nanoparticles for ophthalmic applications. We highlight the potential nanoformulations in clinical trials as well as the products that have become a commercial reality.
One-pot synthesis of poly(β-cyclodextrin) (p(β-CD)) micro-/nanoparticles was accomplished using two different cross-linkers, divinyl sulfone (DVS) as p(β-CD)-1 and trimethylolpropane glycidyl ether (TMPGDE) as p(β-CD)-2. High gravimetric yields of 84 ± 4 and 62 ± 6%, respectively, were attained for p(β-CD)-1 and p(β-CD)-2 particles. The p(β-CD)-1 and p(β-CD)-2 particles had spherical shapes with 5.09 ± 0.24 and 0.60 ± 0.01 μm diameters, respectively, and exhibited good water dispersibility at physiological pH, and their isoelectric points were calculated correspondingly to be pH 1.1 and 1.2. The surface areas of p(β-CD)-1 and p(β-CD)-2 particles were determined to be 4.76 ± 0.6 and 2.18 ± 0.2 m2/g, respectively. Moreover, p(β-CD) particles were found to be biocompatible with more than 98% cell viability on human retinal pigment epithelial (ARPE-19) cells at 0.1 mg/mL concentration. Also, p(β-CD)-1 particles exhibited 52.81 ± 9.5% Fe(II) chelation capacity at 1.0 mg/mL concentration. The hemolysis and coagulation tests revealed that p(β-CD)-1 particles possessed excellent blood compatibility with a 1.18 ± 0.60% hemolysis ratio and a 92.02 ± 1.02% clotting index even at 2.0 mg/mL concentration, whereas the safety limit of p(β-CD)-2 particles for blood interactions was determined to be 0.5 mg/mL. The in vitro drug release performances of p(β-CD)-1 and p(β-CD)-2 particles for hydrophobic acyclovir and hydrophilic vancomycin model drugs at pH 7.4 PBS showed sustained releases of 2.14 ± 0.34 and 1.34 ± 0.43 mg/g acyclovir and 51.90 ± 1.09 and 61.26 ± 3.71 mg/g vancomycin within 24 h, respectively. Kinetic modeling of experimental release data revealed the best fit for drug release from p(β-CD) particles mediated by the Korsmeyer–Peppas model.
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