Effect of Cyclodextrin Complexation of Curcumin on Its Solubility and Antiangiogenic and Anti-inflammatory Activity in Rat Colitis Model

Overview

Journal AAPS PharmSciTech

Publisher Springer

Specialty Pharmacology

Date 2009 Jun 5

PMID 19495987

Citations 47

Authors

Vivek R Yadav

Sarasija Suresh

Kshama Devi

Seema Yadav

Affiliations

Soon will be listed here.

Abstract

The purpose of the study was to prepare and evaluate the anti-inflammatory activity of cyclodextrin (CD) complex of curcumin for the treatment of inflammatory bowel disease (IBD) in colitis-induced rat model. Inclusion complexes of curcumin were prepared by common solvent and kneading methods. These complexes were further evaluated for increase in solubility of poorly soluble curcumin. The inclusion complexes were characterized for enhancement in solubility, in vitro dissolution, surface morphology, infrared, differential scanning calorimetry, and X-ray studies. Solubility, phase solubility, and in vitro dissolution studies showed that curcumin has higher affinity for hydroxypropyl-beta-CD (HPbetaCD) than other CDs. HPbetaCD complex of curcumin was further investigated for its antiangiogenic and anti-inflammatory activity using chick embryo and rat colitis model. HPbetaCD complex of curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in chorioallantoic membrane assay. Curcumin- and HPbetaCD-treated rats showed a faster weight gain compared to dextran sulfate solution (DSS) controls. Whole colon length appeared to be significantly longer in HPbetaCD-treated rats than pure curcumin and DSS controls. An additional finding in the DSS-treated rats was the predominance of eosinophils in the chronic cell infiltrate. Decreased mast cell numbers in the mucosa of the colon of CD of curcumin- and pure-curcumin-treated rats was observed. This study concluded that the degree of colitis caused by administration of DSS was significantly attenuated by CD of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for IBD patients.

Citing Articles

Curcumin Solubility and Bioactivity Enhancement Through Amorphization with Tryptophan via Supercritical Fluid Technology.

Garbiec E, Rosiak N, Sip S, Zalewski P, Cielecka-Piontek J Int J Mol Sci. 2025; 26(2).

PMID: 39859569 PMC: 11766122. DOI: 10.3390/ijms26020855.

Cyclodextrin Drugs in Liposomes: Preparation and Application of Anticancer Drug Carriers.

Feng L, Wei R, Wu J, Chen X, Wen Y, Chen J AAPS PharmSciTech. 2024; 26(1):3.

PMID: 39638889 DOI: 10.1208/s12249-024-02999-0.

Utilizing an Ex Vivo Skin Penetration Analysis Model for Predicting Ocular Drug Penetration: A Feasibility Study with Curcumin Formulations.

Raab C, Brugger S, Lechner J, Barbalho G, Gratieri T, Agarwal P Pharmaceutics. 2024; 16(10).

PMID: 39458631 PMC: 11510696. DOI: 10.3390/pharmaceutics16101302.

Enhancing the solubility and potency of tetrahydrocurcumin as an anti-cancer agent using a β-cyclodextrin inclusion complex approach.

Low Z, Teo M, Nordin F, Palanirajan V, Morak-Mlodawska B, Qazi A PLoS One. 2024; 19(7):e0305171.

PMID: 39058699 PMC: 11280155. DOI: 10.1371/journal.pone.0305171.

Albumin-Based Hydrogel Films Covalently Cross-Linked with Oxidized Gellan with Encapsulated Curcumin for Biomedical Applications.

Tincu Iurciuc C, Daraba O, Jerome C, Popa M, Ochiuz L Polymers (Basel). 2024; 16(12).

PMID: 38931981 PMC: 11207739. DOI: 10.3390/polym16121631.

References

Sharma R, Gescher A, Steward W . Curcumin: the story so far. Eur J Cancer. 2005; 41(13):1955-68. DOI: 10.1016/j.ejca.2005.05.009. View

Pan M, Huang T, Lin J . Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999; 27(4):486-94. View

Wallace J, Macnaughton W, Morris G, Beck P . Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Gastroenterology. 1989; 96(1):29-36. DOI: 10.1016/0016-5085(89)90760-9. View

Hanauer S . Inflammatory bowel disease. N Engl J Med. 1996; 334(13):841-8. DOI: 10.1056/NEJM199603283341307. View

Ruby A, Kuttan G, Babu K, Rajasekharan K, Kuttan R . Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995; 94(1):79-83. DOI: 10.1016/0304-3835(95)03827-j. View

Folkman J, Klagsbrun M . Angiogenic factors. Science. 1987; 235(4787):442-7. DOI: 10.1126/science.2432664. View

Gescher A, Sharma R, Steward W . Cancer chemoprevention by dietary constituents: a tale of failure and promise. Lancet Oncol. 2002; 2(6):371-9. DOI: 10.1016/S1470-2045(00)00392-2. View

Ammon H, Wahl M . Pharmacology of Curcuma longa. Planta Med. 1991; 57(1):1-7. DOI: 10.1055/s-2006-960004. View

Ireson C, Orr S, Jones D, Verschoyle R, Lim C, Luo J . Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res. 2001; 61(3):1058-64. View

10.

Skaper S, Pollock M, Facci L . Mast cells differentially express and release active high molecular weight neurotrophins. Brain Res Mol Brain Res. 2001; 97(2):177-85. DOI: 10.1016/s0169-328x(01)00314-x. View

11.

Podolsky D . Inflammatory bowel disease. N Engl J Med. 2002; 347(6):417-29. DOI: 10.1056/NEJMra020831. View

12.

Holder G, Plummer J, Ryan A . The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat. Xenobiotica. 1978; 8(12):761-8. DOI: 10.3109/00498257809069589. View

13.

Loftsson T, Brewster M . Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996; 85(10):1017-25. DOI: 10.1021/js950534b. View

14.

Cooper H, Murthy S, Kido K, Yoshitake H, Flanigan A . Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation. Carcinogenesis. 2000; 21(4):757-68. DOI: 10.1093/carcin/21.4.757. View

15.

Sharma R, McLelland H, Hill K, Ireson C, Euden S, Manson M . Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001; 7(7):1894-900. View

16.

Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni J, Das P . Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. Br J Pharmacol. 2003; 139(2):209-18. PMC: 1573841. DOI: 10.1038/sj.bjp.0705241. View

17.

Vilaseca J, Salas A, Guarner F, Rodriguez R, Martinez M, Malagelada J . Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis. Gut. 1990; 31(5):539-44. PMC: 1378570. DOI: 10.1136/gut.31.5.539. View

18.

Presta M, Belleri M, Vacca A, Ribatti D . Anti-angiogenic activity of the purine analog 6-thioguanine. Leukemia. 2002; 16(8):1490-9. DOI: 10.1038/sj.leu.2402646. View

19.

Loftsson T, Masson M, Brewster M . Self-association of cyclodextrins and cyclodextrin complexes. J Pharm Sci. 2004; 93(5):1091-9. DOI: 10.1002/jps.20047. View

20.

Rao D, Sekhara N, Satyanarayana M, Srinivasan M . Effect of curcumin on serum and liver cholesterol levels in the rat. J Nutr. 1970; 100(11):1307-15. DOI: 10.1093/jn/100.11.1307. View