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

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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)-block-poly(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 μg/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.

Keywords: CELASTROL; POLYMERIC NANOMICELLES; RESPONSE SURFACE METHODOLOGY; ROTATABLE CENTRAL COMPOSITE DESIGN; RP-HPLC

Document Type: Research Article

DOI: http://dx.doi.org/10.1166/jbn.2012.1398

Publication date: June 1, 2012

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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