Comparisons between a self‐microemulsifying system and lipid nanoparticles of oxyresveratrol on the physicochemical properties and Caco‐2 cell permeability

Abstract

The lipid‐based formulations including an oily self‐microemulsifying drug delivery system (SMEDDS), solid lipid nanoparticles (SLN), and nanostructured lipid carriers (NLC) were developed for the oral delivery of oxyresveratrol (OXYR). Each system was successfully formulated using different optimized compositions and methods. The obtained SMEDDS appeared as a yellow oily liquid, while the SLN and NLC as low viscous suspensions. The physical properties, cytotoxicity, and drug permeability across the Caco‐2 monolayer of the different systems were compared. The non‐aqueous SMEDDS had about a 13‐fold higher drug loading than the lipid nanoparticles. The particle sizes (26.94 ± 0.08 nm) of OXYR‐SMEDDS were significantly smaller than that of the NLC and SLN (p < 0.05). Also, a narrow size distribution of the SMEDDS (PDI, 0.073 ± 0.010) was obtained compared to the lipid nanoparticles (PDI, 0.2–0.3). By using the MTT assay, the OXYR‐SMEDDS showed a fourfold greater toxicity on the Caco‐2 cells than the SLN and NLC containing OXYR. At the non‐toxic concentration of 100 μM of OXYR, the SMEDDS and the lipid nanoparticles had 2.5–3‐fold enhanced permeability and 1.3–1.8‐fold reduced efflux transport compared to the unformulated OXYR (p < 0.05). Practical applications: The improvement of the in vitro oral absorption of the lipid‐based formulations resulted from the increased permeability and inhibited efflux mediated mechanisms. These lipid‐based systems have raised the possibility of the oral OXYR in treating and preventing some importance diseases in future. In addition, these systems could also be used as a potential carrier for oral delivery of other compounds which are substrates for efflux transporters. However, in vivo studies are needed to further investigate oral drug bioavailability. Moreover, for use as a commercial product, it is necessary to improve the storage stability and the toxicity of the oily SMEDDS. The lipid nanoparticles (SLN and NLC) and self‐microemulsifying drug delivery systems (SMEDDS) of oxyresveratrol (OXYR) were produced using different compositions and methods. The appearance and characteristics of the lipid‐based systems were different. However, all of three lipid‐based formulations significantly improved intestinal permeability and reduced efflux transport of OXYR. Therefore, these systems could be used as a potential carrier for oral delivery of OXYR or other compounds which are substrates for efflux transporters.

Lyophilized Hybrid Nanostructured Lipid Carriers to Enhance the Cellular Uptake of Verapamil: Statistical Optimization and In Vitro Evaluation

“…The Caco-2 cells lines is spontaneously differentiating to form monolayer which has significant morphological and biological resemblance to the intestinal epithelium [ 19 ]. Several researchers have reported the in vitro cytotoxicity studies of Compritol ATO 888® [ 20 ], oleic acid [ 21 , 22 ], Tween 80® [ 23 , 24 ], and poloxamer 188 [ 25 ]. These substances were used as excipients in the optimized formulation of HVD-NLCs (VER-9).…”

Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

“…In another study, a self-microemulsifying drug delivery system (SMEDDS) for oral delivery of ORV was developed [ 293 ]. The ORV-SMEDDS showed more favorable physical properties than both the ORV-NLC and the ORV-SLN, with higher drug loading, smaller particle sizes, and narrower size distribution [ 294 ]. All three delivery systems showed enhanced permeability and reduced efflux transport across the Caco-2 monolayer compared to the unformulated ORV.…”

Anti-Inflammatory Activity of Oxyresveratrol Tetraacetate, an Ester Prodrug of Oxyresveratrol, on Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

“…These drawbacks restrict the clinical utility of OXY. Several strategies have been used to improve the physicochemical properties and enhance the pharmacokinetic profile of OXY, such as the use of cyclodextrin encapsulation [17,35,36], nanostructured lipid carriers [5], a self-micro emulsifying drug delivery system [37], cocrystallization [38,39], microemulsion [40], and ester prodrugs [20].…”