Extended levobunolol release from Eudragit nanoparticle-laden contact lenses for glaucoma therapy

Abstract

Background Majorly, the reason for the permanent loss of vision is glaucoma. But the currently available common treatment methodologies such as eye drops have various disadvantages like patient incompliance due to repeated administration and poor (1–5%) bioavailability leading to poor efficiency. The objective of this research was to formulate Eudragit-based nanoparticles of levobunolol incorporated into a contact lens to obtain sustained ocular delivery of levobunolol at the therapeutics level. Eudragit nanoparticles of levobunolol were formulated by nanoprecipitation methodology utilizing different ratios of Eudragit S100 and polyvinyl alcohol. The prepared nanoparticles were evaluated and optimized by efficiency of entrapment, particle size, morphology of surface and zeta potential. The optimized nanoparticles were then entrapped into the matrix of the contact lens by the soaking method which were then characterized and compared for optical clarity study, equilibrium swelling study, shelf life and in vitro drug release in simulated tear fluid followed by ex vivo transcorneal permeation study. Results Formulation F3 was obtained as optimized nanoparticle formulation with 102.61 nm ± 3.92 of particle size, − 22.2 mV ± 2.76 of zeta potential and 86.995% ± 1.902 of efficiency of entrapment. The equilibrium swelling index and transmittance of nanoparticle incorporated into contact lenses showed better results when compared to drug solution-loaded lenses. In vitro release indicated more sustained drug profiles (84.33% ± 0.34 of drug release over a period of 12 days) as compared to drug solution-loaded lenses (89.282% ± 0.900 of drug release over a period of 3 days). Ex vivo transcorneal permeation studies showed more permeation (6.75% ± 0.170) through contact lenses as compared to marketed eye drops (3.03% ± 0.088). Conclusion This research demonstrates the remarkable results of drug-laden contact lenses to serve as a great medium for the continued delivery of ocular drugs without affecting the physical and optical characteristics of the lens content.

Novel Contact Lenses Embedded with Drug-Loaded Zwitterionic Nanogels for Extended Ophthalmic Drug Delivery

“…The light transparency slightly decreased because of the incorporation of PSBMA nanogels. Similar results were also observed by Xu et al [ 27 ] and Maulvi et al [ 28 ] in that the transmittance of contact lenses decreased when nanoparticles were loaded. The Chinese characters (眼means: eyes) under the series of contact lenses show that optical properties were not affected ( Figure 6 b), because the incorporated nanogels were monodispersed and were nano-sized (as can be seen from SEM results), which was not likely to significantly affect visual clarity.…”

“…At the same time, accelerated drug release was achieved in a tear environment (pH 7.4) because of the dissolution of Eudragit S100. Kumar et al [ 28 ] also reported extended levobunolol release from pH-sensitive Eudragit nanoparticle-laden contact lenses for glaucoma therapy. However, the natural aggregation of nanoparticles reduced the optical transparency of contact lenses, and the decreased water content caused by the incorporation of nanoparticles reduced the wear comfort of the contact lenses.…”

Application of Convergent Science and Technology toward Ocular Disease Treatment

“…Kumar et al formulated Eudragit nanoparticles loaded with levobunolol by a soaking method. Loaded lenses’ physical and optical properties were not affected, and controlled long-term release was achieved for levobunolol [ 71 ]. In a rabbit tear fluid model, silicone CLs containing brimonidine-loaded nanoparticles were prepared by Xu et al A high concentration of brimonidine was achieved for 96h with nanoparticle-loaded lenses [ 72 ].…”

Lipase mediated new chemo‐enzymatic synthesis of (RS)‐, (R)‐, and (S)‐bunolol

“…To evaluate the influence of acyl donors, namely, vinyl acetate, benzyl acetate, ethyl acetate, isobutyric anhydride, and butyric anhydride (0.1 mmol) were reacted with (RS)-12 in the presence of CAL L4777 the ee s , ee p , and C were monitored using chiral HPLC. Finally, the enzyme concentration was optimized, by conducting the reactions at optimized substrate concentration (1 mmol) by varying the selected enzyme concentration (10,20,30,40,80, and 120 mg/ml).…”

“…6 The (S)-enantiomer of β-blockers are reported to be more effective in treating diseases involving the β-adrenergic system. [7][8][9][10][11] Smith 12 and Čižm arikov a et al 13 reported that both isomers bind to the heart's β1, β2, and β3 receptors; however, the (S)-isomers have a stronger antagonistic impact because of its longer half-life with higher binding affinity for the β-receptor than the (R)-isomers. (R)-enantiomer has lower affinity for the receptor; eventually, it attaches to other receptors and can lead to undesirable consequences.…”