<p>Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy</p>

Abstract

Background: Peripheral neuropathy is a common and painful side effect that occurs in patients with cancer induced by Oxaliplatin (OXL). The neurotoxicity correlates with the damage of dorsal root ganglion (DRG) neurons and Schwann cells (SCs). Hydroxysafflor yellow A (HSYA), icariin, epimedin B and 3, 4-dihydroxybenzoic acid (DA) are the main neuroprotective ingredients identified in Wen-Luo-Tong (WLT), a traditional Chinese medicinal topical compound. The purpose of this study was to prepare and evaluate the efficacy of an ethosomes gel formulation loaded with a combination of HSYA, icariin, epimedin B and DA. However, the low LogP value, poor solubility and macromolecule are several challenges for topical delivery of these drugs. Methods: Ethosomes were prepared by the single-step injection technique. Particle size, entrapment efficiency and in vitro drug deposition studies were determined to select the optimum ethosomes. The optimized ethosomes were further incorporated into carbopol to obtain a gel. The rheological properties, morphology, in vitro drug release, in vitro gel application and skin distribution of the ethosomes gels were studied. A rat model of oxaliplatin-induced neuropathy was established to assess the therapeutic efficacy of the ethosomes gel. Results: Seventy percent (v/v) ethanol, cinnamaldehyde and Phospholipon 90G were employed to develop ethosomes a carrier system. This system had a high entrapment efficiency, carried large amounts of HSYA, epimedin B, DA and icarrin, and penetrated deep into the epidermis and dermis. The optimized ethosomes had the maximum deposition of icariin, HSYA, epimedin B and relative higher amount of DA in epidermis (2.00±0.13 µg/cm 2 , 5.72 ±0.75 µg/cm 2 , 1.97±0.27 µg/cm 2 and 9.25±1.21 µg/cm 2 , respectively). 0.5% carbopol 980 was selected to develop the ethosomes gel with desirable viscoelasticity and spreadability, which was suitable for topical application. The mechanical allodynia and hyperalgesia induced by OXL in rats were significantly reduced after the new ethosomes gel was applied to rats compared to model group. Conclusion: Based on our findings, the ethosomes gel delivery system provided a new formulation for the topical delivery of HSYA, icariin, epimedin B and DA to counteract OXL-induced peripheral neuropathy.

Formulation and Development of a Water-in-Oil Emulsion-Based Luliconazole Cream: In Vitro Characterization and Analytical Method Validation by RP-HPLC

“…Moreover, in order to sufficiently permeate the drug via the skin, it is required to exhibit appropriate spreading characteristics, desirable viscosity, and improved skin retention time by topical semisolid preparations. Additionally, it is assumed in general that the viscosity of these formulations is directly interrelated with the proportion of polymer [ 31 , 32 ].…”

Ropivacaine‐Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation

“…Then, the use of drug delivery systems is an interesting strategy for developing new and biocompatible pharmaceutical formulations, avoiding injuries to the nerves and spinal cord. In this sense, recent studies report the effects of nanomaterials in Schwann cell cultures looking forward their use for peripheral nerve regeneration by using graphene mesh supported in alginate hydrogels [ 40 ] and polymeric nanoparticles [ 41 ] as well as ethosome-gels for peripheral neuropathy treatment [ 42 ].…”

Platinum-Induced Peripheral Neuropathy (PIPN): ROS-Related Mechanism, Therapeutic Agents, and Nanosystems

“…Considering the poor solubility of the four neuroprotective compounds, they developed ethosome gels by employing ethanol, cinnamaldehyde, phospholipon 90G, and carbopol 980 ( Figure 3A ). The ethosome gel not only significantly alleviated the OXA-induced mechanical allodynia and hyperalgesia but also decreased the numbers of eccentric nuclei of DRG neurons compared with rat model groups ( Figures 3B–D ) ( Lin et al, 2020 ).…”