Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability

Abstract

Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.

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Acknowledgments

The authors would like to acknowledge the financial support from Fujian Kangshimei Co, China, for the present research. Prof. Xin-Fu Zhou is grateful for the NHMRC fellowship. Ankit Parikh is obliged for the University President’s Scholarships from University of South Australia. Also, we thank Lyn Waterhouse from Adelaide Microscopy, The University of Adelaide for the technical support in transmission electron microscopy analysis, Dr. Binoy Sarkar from Centre for Environmental Risk Assessment and Remediation, University of South Australia for X-ray diffraction study, Dr. Nobuyuki Kawashima and Dr. Steve McInnes from Future Industries Institute, University of South Australia, for scanning electron microscopy and differential scanning calorimetry analysis, respectively, H. Md. Morshed Alam (BASF Australia Ltd) for generously providing SOL, and Stephen Philip, a Ph.D. candidate, from School of Pharmacy and Medical Sciences, University of South Australia, for NMR study. The Reid animal house staff members from University of South Australia are acknowledged for generous support in animal work.

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Authors

Contributions

Sanjay Garg (SG) and Xin-Fu Zhou (XFZ) conceived the project. Ankit Parikh (AP), Krishna Kathawala (KK), Yunmei Song (YS), XFZ, and SG designed the study; AP, KK, and XFZ performed the research; AP, KK, YS, XFZ, and SG analyzed the data; AP, KK, XFZ, and SG wrote the paper.

Corresponding authors

Correspondence to Xin-Fu Zhou or Sanjay Garg.

Ethics declarations

All the animal experiments were approved by local animal ethics committee of the University of South Australia under South Australian Animal Welfare Act 1985 and in accordance with an institutional guideline.

Conflict of interest

Ankit Parikh, Xin-Fu Zhou, and Sanjay Garg are the named inventors of Chinese patent 201610267974.5. Fujian Kangshimei Co, China, owns the intellectual property. There is no other potential conflict of interest relevant to this article.

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Parikh, A., Kathawala, K., Song, Y. et al. Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability. Drug Deliv. and Transl. Res. 8, 1389–1405 (2018). https://doi.org/10.1007/s13346-018-0543-3

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Keywords

  • Curcumin
  • Soluplus
  • Solubility
  • Stability
  • Permeability
  • Oral bioavailability