Evaluation of the Influence of Process Parameters on the Properties of Resveratrol-Loaded NLC Using 22 Full Factorial Design

Abstract

Resveratrol (RSV) is a natural antioxidant commonly found in grapes, berries, and nuts that has shown promising results in the treatment of a variety of degenerative and age-related diseases. Despite the proven beneficial results on reduction of reactive oxidant species (ROS) and on inflammatory process, RSV shows various limitations including low long-term stability, aqueous solubility, and bioavailability, restricting its applications in the medical-pharmaceutical area. To overcome these limitations, it has been applied in pharmaceutical formulations as nanostructured lipid carriers (NLC). Thus, the present study focuses on the optimization of the production process of NLC. NLC was produced by high shear homogenization (HSH) and ultrasound method (US) using Compritol® ATO C888 as solid lipid and Miglyol 812® as liquid lipid. In order to obtain an optimized formulation, we used a 22 full factorial design with triplicate of central point investigating the effects of the production process parameters; shear intensity and homogenization time, on the mean particle size (PS) and polydispersity index (PDI). Instability index, encapsulation efficiency, and production yield were also evaluated. As the PS and PDI values obtained with 6 min of shear at 19,000 rpm and 10 min of shear and 24,000 rpm were similar, the instability index (<0.1) was also used to select the optimal parameters. Based on the results of the experimental design and instability index, it was concluded that the shear rate of 19,000 rpm and the shear time of 6 min are the optimal parameters for RSV-loaded NLC production. Factorial design contributed therefore to optimize the variables of the NLC production process from a small number of experiments.

Gefitinib loaded nanostructured lipid carriers: characterization, evaluation and anti-human colon cancer activity in vitro

“…PdI is considered to be an important parameter for physical stability of nanoformulations. Smaller value of PdI is desirable for long term stability of nanosuspensions (Shimojo et al, 2019). Effect of storage period on PdI has been shown in Figure 4.…”

Pure Trans-Resveratrol Nanoparticles Prepared by a Supercritical Antisolvent Process Using Alcohol and Dichloromethane Mixtures: Effect of Particle Size on Dissolution and Bioavailability in Rats

“…Further, its benefits are affected after its oral administration owing to its poor solubility and instability in physiological conditions as well as extensive metabolism [8,9]. To date, several formulation strategies such as amorphous solid dispersions, composite nanoparticles, emulsions, liposomes, polymeric micelles, self-emulsifying drug delivery systems, and solid lipid nanoparticles have been investigated to resolve this problem [10][11][12][13][14][15][16][17][18][19]. In addition, the enhanced oral bioavailability in humans has been reported with lipid formulation, micellar liquid formulation, and microparticles mixed with a liquid formulation [20][21][22].…”

Gelatin-Based Hydrogels for the Controlled Release of 5,6-Dihydroxyindole-2-Carboxylic Acid, a Melanin-Related Metabolite with Potent Antioxidant Activity

“…Severe limitations in this perspective stem from the ease of this compound to undergo oxidation with subsequent loss of its properties. In addition, proper formulation allowing for vehiculation through the skin and a controlled release would greatly add to the beneficial effects prolonging the action and taking the bioavailable concentrations relatively low.In recent years, several natural compounds have been tested for the topical treatment of skin disorders by use of a variety of transcutaneous delivery systems including lipophilic nanoparticles like liposomes [12], solid lipid nanoparticles [13,14], nanostructured lipid carriers, monoolein aqueous dispersions [15,16], ethosomes [17,18], and lecithin organogels [19,20]. Speed up of wound healing process by a nanohydrogel embedding an antioxidant compound like baicalin has been described that exhibited optimal performance for a complete skin restoration and inhibition of specific inflammatory markers [21].A variety of hydrophilic delivery systems have also been explored such as gelatin, the product of collagen hydrolysis, as it offers several advantages including the historical safe use in a wide range of medical applications, low costs, inherent electrostatic binding properties, and proteolytic degradability.…”

“…In recent years, several natural compounds have been tested for the topical treatment of skin disorders by use of a variety of transcutaneous delivery systems including lipophilic nanoparticles like liposomes [12], solid lipid nanoparticles [13,14], nanostructured lipid carriers, monoolein aqueous dispersions [15,16], ethosomes [17,18], and lecithin organogels [19,20]. Speed up of wound healing process by a nanohydrogel embedding an antioxidant compound like baicalin has been described that exhibited optimal performance for a complete skin restoration and inhibition of specific inflammatory markers [21].…”