Encapsulation of Alpha-Lipoic Acid in Functional Hybrid Liposomes: Promising Tool for the Reduction of Cisplatin-Induced Ototoxicity

Abstract

In this study, in order to address the drawback of cisplatin (CDDP)-induced ototoxicity, we propose a straightforward strategy based on the delivery of a sulfur-based antioxidant, such as lipoic acid (LA), to HEI-OC1 cells. To this aim, hybrid liposomes (LA@PCGC) with a spherical shape and a mean diameter of 25 nm were obtained by direct sonication of LA, phosphatidylcholine and a gelatin-curcumin conjugate in a physiological buffer. LA@PCGC were found to be stable over time, were quickly (i.e., by 1 h) taken up by HEI-OC1 cells, and guaranteed strong retention of the bioactive molecule, since LA release was less than 20%, even after 100 h. Cell viability studies showed the efficiency of LA@PCGC for stabilizing the protective activity of LA. Curcumin residues within the functional liposomes were indeed able to maintain the biological activity of LA, significantly improving (up to 2.19-fold) the viability of HEI-OC1 cells treated with 5 μM CDDP. Finally, LA@PCGC was incorporated within an alginate-based injectable hydrogel carrier to create a formulation with physical chemical features suitable for potential ear applications.

Cutting‐Edge Achievements of Inner Ear Drug Delivery Systems

“…They then incorporated alpha lipoic acid into a hybrid nanoformulation composed of phosphatidylcholine and GC. [ 15 ] The nanosystems were rapidly taken up by the cells and their stability was improved, resulting in slow release.…”

Nanotechnological Approaches to Enhance the Potential of α-Lipoic Acid for Application in the Clinic

“…The formulation proved to be stable, enhanced the oral absorption and bioavailability of α-lipoic acid, and improved hepatoprotection in hepatic injury model rats [ 105 ]. Other authors have synthesised new liposomes, consisting of phosphatidylcholine and curcumin, in which α-lipoic acid has been encapsulated; using these liposomes, they demonstrated a high encapsulation efficiency of lipoic acid and its slow release, which countered cisplatin-induced toxicity in HEI-OC1 cells, a cell line utilised as a model for auditory cells [ 106 ].…”

Cisplatin ototoxicity mechanism and antagonistic intervention strategy: a scope review

“…LA@PCGC was injected into company with alginate-based hydrogel carrier to guarantee an appropriate residence time for LA within the administration site. These properties make it become a promising tool for protection from cisplatin-induced ototoxicity ( Curcio et al, 2022 ). The combination of Pifithrin-alpha (PFT-α), d-met, and Neurotrophin-3 (NT3) consisting of an antioxidative, neurotrophic and anti-apoptotic factor given prior to cisplatin exposure has a significant cellular protective effect on cisplatin-induced death ( Febles et al, 2022 ).…”