Curcumin-Encapsulated Chitosan-Coated Nanoformulation as an Improved Otoprotective Strategy for Ototoxic Hearing Loss

Abstract

Overexpression of apoptotic factors in the inner ear is generally proven to induce ototoxicity. This has aroused research interest in various antiapoptotic drugs, the most representative of which is curcumin (CUR). In this study, two nanoformulations of CUR were developed with sustained-release behavior to improve their protective effects against ototoxic hearing loss (HL), which were the nanoparticles of CUR-loaded poly­(lactic acid–glycolic acid) (CUR-PLGA NPs) and CUR-loaded chitosan-coated PLGA NPs (CUR-CS/PLGA NPs). The obtained results revealed that both CUR-NPs provided otoprotection in vitro and in vivo, and their effective doses in guinea pigs were much less than that of dexamethasone, which was clinically used to treat HL. Moreover, relative to CUR and CUR-PLGA NPs, CUR-CS/PLGA NPs exhibited the highest accumulation in HEI-OC1 cells and guinea pigs’ cochlea. In pharmacodynamic experiments, the optimal administration timing was investigated, and CUR-CS/PLGA NPs showed sustained efficacy and the best hearing improvement at all tested sound frequencies. Lastly, the protective effect of CUR nanoformulations was further validated via inhibition of Caspase-3 and Bax activation, thereby reducing the concentration of reactive oxygen species and protecting mitochondrial integrity in hair cells. Collectively, CUR-CS/PLGA NPs demonstrated potent and lasting effects against ototoxic HL, making our novel formulation a promising candidate for the alleviation of sensorineural HL.

Indium Doped Gan Porous Micro‐Rods Enhanced CO2 Reduction Driving By Solar Light

“…By PL and electrochemical analysis, the optimal reduction characteristics of 3%‐In/GaN should be due to the rapid transport and separation of carriers. Mott‐Schottky [ 32,51 ] curve can be used to estimate the energy band position (E CB ) as shown in Figure 8b and Figure S9 (Supporting Information). The pure GaN and In/GaN are n‐type semiconductors with the positive slop.…”

Creation of Chitosan‐Based Nanocapsule‐in‐Nanofiber Structures for Hydrophobic/Hydrophilic Drug Co‐Delivery and Their Dressing Applications in Diabetic Wounds

“…Following the confirmation of the O/W mini‐emulsion formulation for preparing OCS NCs, Cur, a poor water‐soluble anti‐inflammatory agent, was used as a model hydrophobic drug to be loaded into the inner cavity of the NCs. [ 65 ] With a successful encapsulation via the NCs, Cur is considered to exhibit enhanced water solubility, thus broadening the biomedical applicability. Towards this end, Cur was dissolved in the oil template in advance, followed by our developed O/W mini‐emulsion interfacial cross‐linking procedure to prepare Cur‐loaded OCS NCs (Cur‐OCS NCs).…”

Cutting‐Edge Achievements of Inner Ear Drug Delivery Systems

“…[22] Notably, unlike cell-penetrating peptides, the natural polysaccharide chitosan can reversibly open tight junctions in epithelial cells, facilitating paracellular and intercellular transport and improving cellular uptake and distribution of curcumin in the cochlea. [23] Furthermore, there is an ongoing development of smart drug delivery systems that can trigger precisely spatiotemporal controlled release of therapeutic drugs via internal stimuli such as redox, pH, or external stimuli such as light, thermal, and magnetic fields). For instance, Gu et al developed reactive oxygen species (ROS)-responsive nanoparticles that could deliver antioxidants on-demand spatiotemporally.…”

“…[ 22 ] Notably, unlike cell‐penetrating peptides, the natural polysaccharide chitosan can reversibly open tight junctions in epithelial cells, facilitating paracellular and intercellular transport and improving cellular uptake and distribution of curcumin in the cochlea. [ 23 ]…”