Topical ophthalmic lipid nanoparticle formulations (SLN, NLC) of indomethacin for delivery to the posterior segment ocular tissues

Abstract

Purpose The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) and to investigate their potential use in topical ocular delivery. Methods IN SLNs (0.1% w/v) and NLCs (0.8% w/v) were prepared, characterized and evaluated. Their in vitro release and flux profiles across the cornea and sclera-choroid-RPE (trans-SCR) tissues and in vivo ocular tissue distribution were assessed. Furthermore, chitosan chloride (CS) (mol. wt. < 200 kDa), a cationic and water-soluble penetration enhancer, was used to modify the surface of the SLNs, and its effect was investigated through in vitro transmembrane penetration and in vivo distribution tissue studies. Results For the IN-SLNs, IN-CS-SLNs and IN-NLCs, the particle size was 226 ± 5, 265 ± 8, and 227 ± 11 nm, respectively; the zeta potential was −22 ± 0.8, 27 ± 1.2, and −12.2 ± 2.3 mV, respectively; the polydispersity index (PDI) was 0.17, 0.30, and 0.23, respectively; and the entrapment efficiency (EE) was 81 ± 0.9, 91.5 ± 3.2 and 99.8 ± 0.2%, respectively. The surface modification of the SLNs with CS increased the ocular penetration of IN. The NLCs maintained significantly higher IN concentrations in all ocular tissues tested compared to the other formulations evaluated in vivo. Conclusion The results suggest that lipid-based particulate systems can serve as viable vehicles for ocular delivery. The NLC formulations demonstrated increased drug loading capability, entrapment and delivery to anterior and posterior segment ocular tissues.

Development, Characterization and Antidiabetic Potentials of Nilgirianthusciliatus Nees Derived Nanoparticles

“…Biodegradable nanoparticles have been used frequently used as drug delivery vehicles due to their high bioavailability, good encapsulation properties, and relatively lack of toxicity [36]. Different nano-sized carriers, such as nanoparticles, polymeric micelles, liposomes, surface-modified nanoparticles and solid lipid nanoparticles [37][38][39][40], have been developed and suggested for achieving these goals. As the basis for a natural encapsulation agent, gelatin is widely used in a number of formulations because of its biocompatibility, biodegradability, and low antigenicity.…”

Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations

“…Currently, there are few commercial topical formulations specifically intended for the treatment of ocular posterior segment diseases. Even so, in recent years, new advanced topically drug release systems have been developed in order to improve the drug access to the back of the eye, such as nanoparticles [99,118], emulsions [119], nanostructured lipid carriers [120], liposomes [121], and nanosuspensions [122].…”

Ocular disposition of ciprofloxacin from topical, PEGylated nanostructured lipid carriers: Effect of molecular weight and density of poly (ethylene) glycol

“…The bulky and highly hydrated corona of the PEG extending from the lipid bilayer into the aqueous phase is critical for enhancing steric stabilization of the nanoparticles (23). Also, incorporation of PEG could allow better stabilization against aggregation, on storage and on sterilization - by amorphization and inducing imperfections in crystal lipid lattices (24, 25). …”