Potential Eye Drop Based on a Calix[4]arene Nanoassembly for Curcumin Delivery: Enhanced Drug Solubility, Stability, and Anti-Inflammatory Effect

Abstract

Curcumin is an Indian spice with a wide spectrum of biological and pharmacological activities but poor aqueous solubility, rapid degradation, and low bioavailability that affect medical benefits. To overcome these limits in ophthalmic application, curcumin was entrapped in a polycationic calix[4]arene-based nanoaggregate by a simple and reproducible method. The calix[4]arene-curcumin supramolecular assembly (Calix-Cur) appeared as a clear colloidal solution consisting in micellar nanoaggregates with size, polydispersity index, surface potential, and drug loading percentage meeting the requirements for an ocular drug delivery system. The encapsulation in the calix[4]arene nanoassembly markedly enhanced the solubility, reduced the degradation, and improved the anti-inflammatory effects of curcumin compared to free curcumin in both in vitro and in vivo experiments. Calix-Cur did not compromise the viability of J774A.1 macrophages and suppressed pro-inflammatory marker expression in J774A.1 macrophages subjected to LPS-induced oxidative stress. Histological and immunohistochemical analyses showed that Calix-Cur reduced signs of inflammation in a rat model of LPS-induced uveitis when topically administrated in the eyes. Overall, the results supported the calix[4]arene nanoassembly as a promising nanocarrier for delivering curcumin to anterior ocular tissues.

Palladium Nanoparticles Fabricated by Green Chemistry: Promising Chemotherapeutic, Antioxidant and Antimicrobial Agents

“…Finally, the biosynthesized Pd NPs are purified and washed via centrifugation [ 51 ]. It is worth mentioning that few recent studies reported on the use of supramolecules (macromolecules) such as calix[n]arenes and cyclodextrins as potential stabilizing agents for the biosynthesized Pd NPs [ 52 , 53 , 54 , 55 , 56 ]. They have been chosen as promising capping agents due to their biocompatible and eco-friendly nature [ 57 ].…”

Synthesis and Conformational Characteristics of Thermosensitive Star-Shaped Six-Arm Polypeptoids

“…It was shown that transition from linear to star-shaped macromolecules significantly increases the polymer's ability of molecular recognition [3,4]. Special attention is paid to the derivatives of polyethylene oxide and polyalkyloxazolines, which is resulting from their biocompatibility and the ability to show low critical solution temperature (LCST) behavior, which allows controlling the processes of complexation of low-molecular compounds [5][6][7][8]. It should be pointed out that incorporation into the polymer of such moieties as macrocycles, for example calixarenes, cyclodextrins, etc., leads to a significant increase of the affinity of these macromolecules to low-molecular compounds and metal ions.…”

Curcumin as a Therapeutic Option in Retinal Diseases

“…A rat model of anterior uveitis, induced by LPS was also evaluated with the same results, the application of curcumin/calix [4]arene decreased ocular inflammation and reduced inflammation proteins to a higher extent than free curcumin. It also reduced ICAM-1 by the suppression of NF-κB [95].…”