Optimized Preparation of Celastrol-Loaded Polymeric Nanomicelles Using Rotatable Central Composite Design and Response Surface Methodology

Abstract

Celastrol has been found to be a potent anti-inflammatory and antitumor plant derivative recently. Herein we established an accurate reverse phase HPLC (RP-HPLC) determination method of celastrol, and prepared an effective nanoscale drug delivery system from the optimized formulations of celastrol-loaded carboxyl functioned poly(ethylene glycol)-block-poly(propylene glycol)-blockpoly(ethylene glycol)(PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles. Rotatable central composite design (RCCD) and response surface methodology (RSM) were applied to improve the celastrol entrapment efficiency (EE), drug loading percentage (DLP), and decrease the particle size. The characteristics of the optimized micelles including particle size distribution, morphology, zeta potential and in vitro release of celastrol from micelles were carried out. Results showed that RP-HPLC method was successfully applied to detect and qualify the celastrol. The drug quantification range of the method was 20-200 g/mL with a linear correlation coefficient of greater than 0.999. The average accuracy (99.763%), the precision (0.521%) and recovery (99.63%) for this method were good. The optimal conditions for the preparation of celastrol-loaded polymeric nanomicelles were found to be: the celastrol/polymer weight ratio 8.5-9 mg/25 mg, hydration volume 11-17 mL. Under the optimal conditions, the EE was 100 3 ± 4 3%, DLP was 22 8 ± 1 0%, the average particle size was 117 3 ± 1 27 nm and the zeta potential was −2 19 ± 0 15 mV. Transmission electron micrograph (TEM) showed the micelles to be oval and rodlike shaped, with mean diameter around 20 nm. The in vitro experiments proved that celastrol in polymeric nanomicelles released gradually over the period of 24 h. These results showed that the RCCD and RSM could efficiently be applied for optimized preparation of celastrol-loaded polymeric nanomicelles.

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

“…To surpass the physicochemical and pharmacokinetic limitations of celastrol and to diminish the effective dose, several methodologies have been tested that can represent useful strategies, such as exosomes (200), lipid nanospheres (201), nanoencapsulation (202), polyamidoamine dendrimer nanocarriers (203), liposomes (204–206), polymeric micelles (207, 208), cell-penetrating peptides-coated nanostructured lipid carriers (194, 209–211), sugar-silica nanoparticles (212), and self-microemulsifying drug delivery system (193). For instance, recent data have shown that celastrol-loaded exosomes enhance free celastrol efficacy and reduce dose-related toxicity in lung cancer (200).…”

Celastrol Nanoemulgel Formulation and in Vitro Penetration Test

“…The procedure was carried out by taking 0.2 µl of a Celastrol nanoemulgel preparation using uranyl acetate dye 2% (w/v) 0.2 µl, which was dripped on the cooper grid plate. Furthermore, observations were made at a magnifications of 30,000, 50,000 and 100,000 times [25,26].…”

“…The method was developed into peroral, IP, and topical routes. The study results concluded that Celastrol developed into nanotechnology increased the absorption efficiency (EE) to 98.06% with an average particle size of 89.6±7.3 nm ≤100 nm and zeta potential of 87.8±5.8 mV [4][5][6][7][8].…”

Oral Bioavailability Evaluation of Celastrol-Encapsulated Silk Fibroin Nanoparticles Using an Optimized LC-MS/MS Method

“…Nevertheless, the reliable determination methods are essential for the precise pharmacokinetics of the analyte and its novel formulations. Till now, some determination methods of CL in plasma based on HPLC technology and their application in pharmacokinetic studies have been reported [ 18 , 19 , 20 , 21 ]. However, the insufficient selectivity and sensitivity of HPLC methods apparently limit their wide application on in vivo pharmacokinetics such as oral bioavailability studies of CL loaded drug delivery systems.…”