Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

Abstract

Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems

“…Due to the diverse benefits of sustained and controlled drug release, high physical stability, low degradation of lipids, in vivo acceptability, and applicability to different administration routes makes lipid nanoparticles a very adaptive and effective carrier for various drug-delivery systems [ 147 ]. Lipid nanoparticles especially liposomes, solid-lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and nanoemulsions have the potential ability to entrap both lipophobic and lipophilic drugs, enhance the bioavailability of low aqueous soluble drugs, and protect them against untimely degradation.…”

“…Recent investigation showed tremendous potential of nanoparticle-based buccal drug-delivery systems to furnish enhanced localization and drug targeting. The SLN is considered to be an efficient nano-drug-delivery carrier used for a broad range of drugs delivered through either oral or non-oral routes [ 147 ]. For successful buccal delivery, prolonged contact with SLN and buccal mucosa is important to minimize loss of drug due to saliva turnover, swallowing and chewing, tongue movements and phonation.…”

Lung Targeted Lipopolymeric Microspheres of Dexamethasone for the Treatment of ARDS

“…For the determination of particle size, the microspheres were suspended in normal saline and the size distribution was analyzed using laser diffraction analysis (Malvern Mastersizer 300, Malvern, UK) [ 25 ]. The particle size was expressed as volume-weighted mean diameter in micrometers [ 26 ].…”

The Emerging Role of Topical Ocular Drugs to Target the Posterior Eye

“…Besides the formulations mentioned above, many other forms of nanomedicines, including nanoemulsion [121], quantum dot [122], solid-lipid nanoparticle [123], and so on, have been investigated as topical ocular drug carriers and demonstrate beneficial efficacy. As an example, dexamethasone carried by soluble nanoparticle (drug name OCS-01) developed by Oculis is now in a phase III clinical trial for DME.…”