In Vitro Skin Permeation of Idebenone from Lipid Nanoparticles Containing Chemical Penetration Enhancers

Abstract

Lipid nanoparticles (LNPs) have been proposed as carriers for drug skin delivery and targeting. As LNPs effectiveness could be increased by the addition of chemical penetration enhancers (PE), in this work, the feasibility of incorporating PE into LNPs to improve idebenone (IDE) targeting to the skin was investigated. LNPs loading IDE 0.7% w/w were prepared using hydrophilic (propylene glycol, PG, 10% w/w or N-methylpyrrolidone, NMP, 10% w/w) and/or lipophilic PE (oleic acid, OA, 1% w/w; isopropyl myristate, IPM, 3.5% w/w; a mixture of 0.5% w/w OA and 2.5% w/w IPM). All LNPs showed small sizes (<60 nm), low polydispersity index and good stability. According to the obtained results, IDE release from LNPs was not the rate-limiting step in IDE skin penetration. No IDE permeation was observed through excised pigskin from all LNPs, while the greatest increase of IDE penetration into the different skin layers was obtained using the mixture OA/IPM. The antioxidant activity of IDE-loaded LNPs, determined by the oxygen radical absorbance capacity assay, was greater than that of free IDE. These results suggest that the use of suitable PE as LNPs components could be regarded as a promising strategy to improve drug targeting to the skin.

Multidrug Idebenone/Naproxen Co‐loaded Aspasomes for Significant in vivo Anti‐inflammatory Activity

“…To overcome these drawbacks and preserve the stability and activity of Idebenone, nanocarriers with suitable physicochemical properties have been synthesized. [30] Moreover, Idebenone does not have suitable physicochemical and biopharmaceutical properties, like sodium naproxen, to pass by stratum corneum epidermis and reach the epidermis or derma where the anti-inflammatory effects are required. [31] For these reasons, Idebenone and naproxen were co-loaded into aspasomes, thus providing a multidrug nanocarrier which further improves the anti-inflammatory properties that aspasomes had per se.…”

“…Moreover, Idebenone is quickly inactivated after exposition to UV‐Vis light with a resulting decrease of its antioxidant activity. To overcome these drawbacks and preserve the stability and activity of Idebenone, nanocarriers with suitable physicochemical properties have been synthesized [30] . Moreover, Idebenone does not have suitable physicochemical and biopharmaceutical properties, like sodium naproxen, to pass by stratum corneum epidermis and reach the epidermis or derma where the anti‐inflammatory effects are required [31] …”

Solid Lipid Nanoparticles as Carriers for the Synthetic Opioid LP2: Characterization and In Vitro Release

“…SLNs with similar technological properties (small mean size, low PDI and ζ-potential values, and good stability during storage at room temperature) were obtained in previous works using the PIT method [23]. The presence of long polyoxyethylene chains of the surfactant oleth-20 on the nanoparticle surface, which could provide a steric stabilization, was considered responsible for the good stability of the resulting nanocarriers [23]. As illustrated in Table 1, LP2-loaded SLNs showed a PIT value greater than that of unloaded SLN, thus suggesting different interactions among the lipid core components in the presence of LP2.…”

“…All samples remained clear during the storage period with no sign of drug precipitation. SLNs with similar technological properties (small mean size, low PDI and ζ-potential values, and good stability during storage at room temperature) were obtained in previous works using the PIT method [23]. The presence of long polyoxyethylene chains of the surfactant oleth-20 on the nanoparticle surface, which could provide a steric stabilization, was considered responsible for the good stability of the resulting nanocarriers [23].…”

“…SLNs were prepared using the phase-inversion temperature (PIT) as previously reported [23,24]. The oil phase components were CP (7,0% w/w, solid lipid), oleth-20, (8.7% w/w, surfactant), GO (4.4% w/w, co-surfactant), and LP2 (1.1% w/w), while the aqueous phase consisted of saline solution (NaCl 0.90% w/w).…”