Curcumin (CUR) has various pharmacological effects, but its extensive first-pass metabolism and short elimination half-life limit its bioavailability. Therefore, transdermal application has become a potential alternative to delivery CUR. To increase CUR solubility for the development of a transparent homogenous gel and also enhance the permeation rate of CUR into the skin, β-cyclodextrin–curcumin nanoparticle complex (BCD–CUR-N) was developed. CUR encapsulation efficiency was increased by raising the percentage of CUR to BCD up to 20%. The mean particle size of the best CUR loading formula was 156 nm. All evaluation data using infrared spectroscopy, Raman spectroscopy, powder X-ray diffractometry, differential thermal analysis and scanning electron microscopy confirmed the successful formation of the inclusion complex. BCD–CUR-N increased the CUR dissolution rate of 10-fold (p < 0.01). In addition, the improvement of CUR permeability acrossed skin model tissue was observed in gel containing the BCD–CUR-N and was about 1.8-fold when compared with the free CUR gel (p < 0.01). Overall, CUR in the form of the BCD–CUR-N improved the solubility further on the penetration of CUR.
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Maheswari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci. 2006;78(18):2081–7. doi:10.1016/j.lfs.2005.12.007.
De R, Kundu P, Swarnakar S, Ramamurthy T, Chowdhury A, Nair GB, et al. Antimicrobial activity of curcumin against Helicobacter pylori isolates from India and during infections in mice. Antimicrob Agents Chemother. 2009;53(4):1592–7. doi:10.1128/AAC.01242-08.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64(4):353–6.
Anand P. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharma. 2008;76:1590–611. doi:10.1016/j.bcp.2008.08.008.
Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999;27(4):486–94.
Garcea G, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, et al. Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer. 2004;90(5):1011–5. doi:10.1038/sj.bjc.6601623.
Alonso A, Meirelles NC, Yushmanov VE, Tabak M. Water increases fluidity of intercellular membranes of stratum corneum: correlation with water permeability, elastic, and electrical resistance properties. J Invest Dermatol. 1996;106:1058–63. doi:10.1111/1523-1747.
Sparr E, Wennerström H. Responding phospholipid membranes—interplay between hydration and permeability. Biophys J. 2001;81:1014–28.
Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85(10):1017–25.
Vivek RY, Sarasija S, Kshama D, Seema Y. Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti-inflammatory activity in rat colitis model. AAPS Pharm Sci Tech. 2009;10(3):752–62. doi:10.1208/s12249-009-9264-8.
Kazemi F, Zaraghami N, Fekri aval S, Monfaredan A. β-Cyclodextrin–curcumin complex inhibit telomerase gene expression in T47-D breast cancer cell line. African J Biotechnol. 2011;10(83):19481–8.
Yallapu MM, Jaggi M, Chauhan SC. β-Cyclodextrin–curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids Surf B: Biointerfaces. 2010;79:113–25. doi:10.1016/j.colsurfb.2010.03.039.
Loftsson T, Masson M. Cyclodextrins in topical drug formulations: theory and practice. Int J Pharm. 2001;225:15–30. doi:10.1016/S0378-5173(01)00761-X.
Sznitowska M, Janicki S, Williams AC. Intracellular or intercellular localization of the polar pathway of penetration across stratum corneum. J Pharm Sci. 1998;87:1109–14. doi:10.1021/js980018w.
Jayaprakasha GK, Rao LJM, Sakariah KK. Improved HPLC method for the determination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin. J Agric Food Chem. 2002;50(13):3668–72. doi:10.1021/jf025506a.
Darandale SS, Vavia PR. Cyclodextrin-based nanosponges of curcumin: formulation and physicochemical characterization. J Incl Phenom Macrocycl Chem. 2012;74(1–4):145–55.
Sourabhan S, Kaladhar K, Sharma CP. Method to enhance the encapsulation of biologically active molecules in PLGA nanoparticles. Trends Biomater Artif Organs. 2009;22(3):211–5.
Spivey R, Swofford RL. Inclusion complexes of N-benzoyl-d-leucine and N-benzoyl-l-leucine with beta-cyclodextrin by Raman spectroscopy. Appl Spectrosc. 1999;53:435–8. doi:10.1366/0003702991946893.
Frank CJ. Review of pharmaceutical applications of Raman spectroscopy. In: Pelletier MJ, editor. Analytical applications of Raman spectroscopy. UK: Blackwell Science; 1999. p. 224–71.
Rossi B, Verrocchio P, Villiani G. Vibrational dynamics of inclusion complexes by Raman scattering: an experimental and numerical study. Phil Mag. 2007;87:559.
Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23:363–98.
Sanphui P, Goud NR, Khandavilli UBR, Bhanoth S, Nangia A. New polymorphs of curcumin. Chem Commun. 2011;47:5013–5. doi:10.1080/14786430600887657.
Lin SY, Hou SJ, Hsu TH, Yeh FL. Comparisons of different animal skins with human skin in drug percutaneous penetration studies. Methods Find Exp Clin Pharmacol. 1992;14:645–54.
Egawa M, Hirao T, Takahashi M. In vivo estimation of stratum corneum thickness from water concentration profiles obtained with Raman spectroscopy. Acta Derm Venereol. 2007;87:4–8.
Loftsson T, Masson M, Brewster ME. Self-association of cyclodextrins and cyclodextrin complexes. J Pharm Sci. 2004;93:1091–9.
Pugh WJ, Hadgraft J, Roberts MS. Physicochemical determinants of stratum corneum permeation. In: Roberts MS, Walters KA, editors. Dermal absorption and toxicity assessment. New York: Marcel Dekker; 1998. p. 245–68.
Babu RJ, Pandit JK. Effect of cyclodextrins on the complexation and transdermal delivery of bupranolol through rat skin. Int J Pharm. 2004;271:155–65. doi:10.1016/j.ijpharm.2003.11.004.
This work was financially supported by the Indonesia Managing High Education for Relevance and Efficiency Program, Bandung Institute of Technology 2012.
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Rachmawati, H., Edityaningrum, C.A. & Mauludin, R. Molecular Inclusion Complex of Curcumin–β-Cyclodextrin Nanoparticle to Enhance Curcumin Skin Permeability from Hydrophilic Matrix Gel. AAPS PharmSciTech 14, 1303–1312 (2013). https://doi.org/10.1208/s12249-013-0023-5
- diffusion kinetic
- hydrophilic gel
- skin permeation