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Comparison and correlation of in vitro, in vivo and in silico evaluations of alpha, beta and gamma cyclodextrin complexes of curcumin

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Abstract

In the present study investigated the effect of curcumin (CUR) alpha (α), beta (β) and gamma (γ) cyclodextrin (CD) complexes on its solubility and bioavailability. CUR the active principle of turmeric is a natural antioxidant agent with potent anti-inflammatory activity along with chemotherapeutic and chemopreventive properties. Poor solubility and poor oral bioavailability are the main reasons which preclude CUR use in therapy. Extent of complexation was β-CD complex (82 %) > γ-CD (71 %) > α-CD (65 %). Pulverization method resulted in significant enhancement of CUR (0.002 mg/ml) solubility with CUR α-CD complex (0.364 mg/ml) > CUR β-CD complex (0.186 mg/ml) > CUR γ-CD complex (0.068 mg/ml). Gibbs-free energy and in silico molecular docking studies favour formation of α-CD complex > β-CD complex > γ-CD complex. With reference to CUR, relative bioavailability of CUR α-CD, CUR β-CD and CUR γ-CD complexes were 460, 365 and 99 % respectively. CUR–CD complexes exhibited increased bioavailability with an increase in t½, tmax, Cmax, AUC, Ka, and MRT; and a decrease in Ke, clearance and Vd values. AUC increase was CUR α-CD complex > CUR β-CD complex > CUR γ-CD complex. Significant difference (p < 0.05) was observed between CUR α-CD complex and CUR γ-CD complex by one-way ANOVA and Dunnett’s post hoc test for multiple comparison analysis. Correlation observed between in vitro, in vivo and in silico methods indicates potential of in silico and in vitro methods in CD selection.

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Acknowledgments

Authors would like to thank Prof. B.G. Shivananda, Principal, Al-Ameen College of Pharmacy for his kind support and encouragement to carry out this project.

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Authors and Affiliations

  1. Al-Ameen College of Pharmacy, Hosur Road, Bangalore, 560027, India

    Nagaraju M. Patro, Azmi Sultana, Raghu N. Gorantla, Vinay Pandit, Kshama Devi, Anand Suresh & Sarasija Suresh

  2. Cyclochem Co., Ltd, Tokyo, Japan

    Keiji Terao, Daisuke Nakata, Ayako Jo, Akihito Urano & Yoshiyuki Ishida

  3. National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India

    Shishir Rohit, Baljinder K. Grewal, Elizabeth M. Sophia, Vineeth K. Ekbote & Sarasija Suresh

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Patro, N.M., Sultana, A., Terao, K. et al. Comparison and correlation of in vitro, in vivo and in silico evaluations of alpha, beta and gamma cyclodextrin complexes of curcumin. J Incl Phenom Macrocycl Chem 78, 471–483 (2014). https://doi.org/10.1007/s10847-013-0322-1

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