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Current Nanoscience

Editor-in-Chief

ISSN (Print): 1573-4137
ISSN (Online): 1875-6786

Research Article

Usefulness of Lipidic Nanoparticles of Curcumin and Tetrahydrocurcumin for Skin Inflammation: A Comparative Study

Author(s): Komal Saini, Manoj Kumar Verma, Indu Pal Kaur and Vandita Kakkar*

Volume 19, Issue 4, 2023

Published on: 09 September, 2022

Page: [549 - 558] Pages: 10

DOI: 10.2174/1573413718666220414151940

Price: $65

Abstract

Background: Yellow curcumin, the “Indian Gold” has been known since ancient times to modulate the activities of a wide variety of targets. The voluminous literature and several patents are proof of the therapeutic value of curcumin. Tetrahydrocurcumin (THC), however, has remained an unexplored molecule, although its cosmeceutical properties have been documented. Their compromised bioavailability, poor aqueous solubility (curcumin 11 ng/mL, THC 56ng/mL), and high log P (Cur: 3.28; THC: 2.98) are hurdles to being developed as potential drugs.

Objective: This article discusses the usefulness of lipidic nanoparticles of curcumin and THC for skin inflammation.

Method: Nanocouturing to produce lipidic nanoparticles (LNs) of curcumin and THC was done via an optimized microemulsification technique. LNs were characterized by FTIR, TEM, pharmacokinetics, and pharmacodynamic study.

Results: FTIR reflected the suitable incorporation of drugs into LNs. TEM examination revealed a spherical to ellipsoidal shape with a particle size of <200 nm. In vitro release study indicated that the release of both drugs was between 70-80% within 24 h. Ex vivo permeation studies confirmed the ability of LNs to cross the stratum corneum. Stability studies (Q1AR2) indicated that both were stable, safe, and non-irritating (OECD 404). Xylene-induced ear edema model of inflammation showed both molecules to possess equivalent abilities to treat inflammation.

Conclusion: Curcumin, being yellow coloured, is unstable at physiological pH and plasma and possesses poor bioavailability, while THC is a colorless stable molecule, making it a molecule of choice to be developed as an effective topical product.

Keywords: Curcumin, tetrahydrocurcumin, lipidic nanopaticles, pharmacodynamic study

Graphical Abstract

[1]
Corson, T.W.; Crews, C.M. Molecular understanding and modern application of traditional medicines: Triumphs and trials. Cell, 2007, 130(5), 769-774.
[http://dx.doi.org/10.1016/j.cell.2007.08.021] [PMID: 17803898]
[2]
Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: Problems and promises. Mol. Pharm., 2007, 4(6), 807-818.
[http://dx.doi.org/10.1021/mp700113r] [PMID: 17999464]
[3]
Madhu; Kaushik, D. Design and development of curcumin loaded nanoparticles for antibacterial activity. J. Emerg. Technol. Innov. Res., 2021, 8(12), 65-81.
[4]
Paul, S.; Mohanram, K.; Kannan, I. Antifungal activity of curcumin-silver nanoparticles against fluconazole-resistant clinical isolates of Candida species. Ayu, 2018, 39(3), 182-186.
[http://dx.doi.org/10.4103/ayu.AYU_24_18] [PMID: 31000996]
[5]
Loutfy, S.A.; Elberry, M.H.; Farroh, K.Y.; Mohamed, H.T.; Mohamed, A.A.; Mohamed, E.B.; Faraag, A.H.I.; Mousa, S.A. Antiviral activity of chitosan nanoparticles encapsulating curcumin against hepatitis C virus genotype 4a in human hepatoma cell lines. Int. J. Nanomedicine, 2020, 15, 2699-2715.
[http://dx.doi.org/10.2147/IJN.S241702] [PMID: 32368050]
[6]
Abu-Taweel, G.M.; Attia, M.F.; Hussein, J.; Mekawi, E.M.; Galal, H.M.; Ahmed, E.I.; Allam, A.A.; El-Naggar, M.E. Curcumin nanoparticles have potential antioxidant effect and restore tetrahydrobiopterin levels in experimental diabetes. Biomed. Pharmacother., 2020, 131, 110688.
[http://dx.doi.org/10.1016/j.biopha.2020.110688] [PMID: 33152905]
[7]
Kakkar, V.; Kaur, I.P. Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium induced behavioural, biochemical and histopathological alterations in mice brain. Food Chem. Toxicol., 2011, 49(11), 2906-2913.
[http://dx.doi.org/10.1016/j.fct.2011.08.006] [PMID: 21889563]
[8]
Kakkar, V.; Singh, S.; Singla, D.; Kaur, I.P. Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Mol. Nutr. Food Res., 2011, 55(3), 495-503.
[http://dx.doi.org/10.1002/mnfr.201000310] [PMID: 20938993]
[9]
Kakkar, V.; Mishra, A.K.; Chuttani, K.; Kaur, I.P. Proof of concept studies to confirm the delivery of curcumin loaded solid lipid nanoparticles (C-SLNs) to brain. Int. J. Pharm., 2013, 448(2), 354-359.
[http://dx.doi.org/10.1016/j.ijpharm.2013.03.046] [PMID: 23558314]
[10]
Wang, J.; Wang, H.; Zhu, R.; Liu, Q.; Fei, J.; Wang, S. Anti-inflammatory activity of curcumin-loaded solid lipid nanoparticles in IL-1β transgenic mice subjected to the lipopolysaccharide-induced sepsis. Biomaterials, 2015, 53, 475-483.
[http://dx.doi.org/10.1016/j.biomaterials.2015.02.116] [PMID: 25890744]
[11]
Siwak, D.R.; Shishodia, S.; Aggarwal, B.B.; Kurzrock, R. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer, 2005, 104(4), 879-890.
[http://dx.doi.org/10.1002/cncr.21216] [PMID: 16007726]
[12]
Kaur, I.P.; Kakkar, V. Bioavailability enhancement and brain targeting of curcumin: A potential antitumor agent. ChemInfor, 2012, 43(40)
[http://dx.doi.org/10.1002/chin.201240250]
[13]
Aggarwal, B.B.; Deb, L.; Prasad, S. Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses. Molecules, 2014, 20(1), 185-205.
[http://dx.doi.org/10.3390/molecules20010185] [PMID: 25547723]
[14]
Somparn, P.; Phisalaphong, C.; Nakornchai, S.; Unchern, S.; Morales, N.P. Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol. Pharm. Bull., 2007, 30(1), 74-78.
[http://dx.doi.org/10.1248/bpb.30.74] [PMID: 17202663]
[15]
Kadoma, Y.; Fujisawa, S. Comparative radical-scavenging activity of curcumin and tetrahydrocurcumin with thiols as measured by the induction period method. In Vivo, 2007, 21(6), 979-982.
[PMID: 18210744]
[16]
Sugiyama, Y.; Kawakishi, S.; Osawa, T. Involvement of the beta-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem. Pharmacol., 1996, 52(4), 519-525.
[http://dx.doi.org/10.1016/0006-2952(96)00302-4] [PMID: 8759023]
[17]
Hong, J.; Lambert, J.D.; Lee, S.H.; Sinko, P.J.; Yang, C.S. Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites. Biochem. Biophys. Res. Commun., 2003, 310(1), 222-227.
[http://dx.doi.org/10.1016/j.bbrc.2003.09.007] [PMID: 14511674]
[18]
Dileep, K.V.; Tintu, I.; Sadasivan, C. Molecular docking studies of curcumin analogs with phospholipase A2. Interdiscip. Sci., 2011, 3(3), 189-197.
[http://dx.doi.org/10.1007/s12539-011-0090-9] [PMID: 21956741]
[19]
Ayli, E.E.; Dugas-Breit, S.; Li, W.; Marshall, C.; Zhao, L.; Meulener, M.; Griffin, T.; Gelfand, J.M.; Seykora, J.T. Curcuminoids activate p38 MAP kinases and promote UVB-dependent signalling in keratinocytes. Exp. Dermatol., 2010, 19(6), 493-500.
[http://dx.doi.org/10.1111/j.1600-0625.2010.01081.x] [PMID: 20456495]
[20]
Kakkar, V.; Kaur, I.P.; Kaur, A.P.; Saini, K.; Singh, K.K. Topical delivery of tetrahydrocurcumin lipid nanoparticles effectively inhibits skin inflammation: In vitro and in vivo study. Drug Dev. Ind. Pharm., 2018, 44(10), 1701-1712.
[http://dx.doi.org/10.1080/03639045.2018.1492607] [PMID: 29938544]
[21]
Torres-Torres, C.; Morales-Bonilla, S.; Mota-Díaz, I.I.; Douda, J.; González-Vargas, C.R.; Villalpando, I. Thermo-mechanical effects and photo-induced release of liposome-encapsulated nanodiamonds by polarization-resolved laser pulses. Optik (Stuttg.), 2021, 245, 167738.
[http://dx.doi.org/10.1016/j.ijleo.2021.167738]
[22]
Triplett, M.D.; Rathman, J.F. Optimization of β-carotene loaded solid lipid nanoparticles preparation using a high shear homogenization technique. J. Nanopart. Res., 2009, 11, 601-614.
[http://dx.doi.org/10.1007/s11051-008-9402-3]
[23]
Crave, V.O.; Faghihzadeh, F.; Anaya, N.M.; Schifman, L.A. Fourier transform infrared spectroscopy to assess molecular-level changes in microorganisms exposed to nanoparticles. Nanotechnol. Environl. Eng., 2016, 1, 1-16.
[http://dx.doi.org/10.1007/s41204-016-0001-8]
[24]
ICH. Harmonised tripartite guideline stability testing of new drug substances and products Q1A (R2). 2003.
[25]
De Sousa Marcial, S.P.; Carneiro, G.; Leite, E.A. Lipid-based nanoparticles as drug delivery system for paclitaxel in breast cancer treatment. J. Nanopart. Res., 2017, 19, 340.
[http://dx.doi.org/10.1007/s11051-017-4042-0]
[26]
OECD. OECD guideline for testing of chemicals 404. 2002.
[27]
Manaia, E.B.; Abuçafy, M.P.; Chiari-Andréo, B.G.; Silva, B.L.; Oshiro, Junior, J.A.; Chiavacci, L.A. Physicochemical characterization of drug nanocarriers. Int. J. Nanomedicine, 2017, 12, 4991-5011.
[http://dx.doi.org/10.2147/IJN.S133832] [PMID: 28761340]
[28]
El-Gizawy, S.A.; El-Maghraby, G.M.; Hedaya, A.A. Formulation of acyclovir-loaded solid lipid nanoparticles: Design, optimization, and in vitro characterization. Pharm. Dev. Technol., 2019, 24(10), 1287-1298.
[http://dx.doi.org/10.1080/10837450.2019.1667385] [PMID: 31507232]
[29]
Rajan, S.S.; Pandian, A.; Palaniappan, T. Curcumin loaded in bovine serum albumin–chitosan derived nanoparticles for targeted drug delivery. Bull. Mater. Sci., 2016, 39(3), 811-817.
[http://dx.doi.org/10.1007/s12034-016-1213-z]
[30]
Davis, B.M.; Pahlitzsch, M.; Guo, L.; Balendra, S.; Shah, P.; Ravindran, N.; Malaguarnera, G.; Sisa, C.; Shamsher, E.; Hamze, H.; Noor, A.; Sornsute, A.; Somavarapu, S.; Cordeiro, M.F. Topical curcumin nanocarriers are neuroprotective in eye disease. Sci. Rep., 2018, 8(1), 11066.
[http://dx.doi.org/10.1038/s41598-018-29393-8] [PMID: 30038334]
[31]
Shrotriya, S.; Ranpise, N.; Satpute, P.; Vidhate, B. Skin targeting of curcumin solid lipid nanoparticles-engrossed topical gel for the treatment of pigmentation and irritant contact dermatitis. Artif. Cells Nanomed. Biotechnol., 2018, 46(7), 1471-1482.
[http://dx.doi.org/10.1080/21691401.2017.1373659] [PMID: 28884598]
[32]
Wang, W.; Chen, T.; Xu, H.; Ren, B.; Cheng, X.; Qi, R.; Liu, H.; Wang, Y.; Yan, L.; Chen, S.; Yang, Q.; Chen, C. Curcumin-loaded solid lipid nanoparticles enhanced anticancer efficiency in breast cancer. Molecules, 2018, 23(7), 1578.
[http://dx.doi.org/10.3390/molecules23071578] [PMID: 29966245]
[33]
Barros, S.M.; Whitaker, S.K.; Sukthankar, P.; Avila, L.A.; Gudlur, S.; Warner, M.; Beltrão, E.I.; Tomich, J.M. A review of solute encapsulating nanoparticles used as delivery systems with emphasis on branched amphipathic peptide capsules. Arch. Biochem. Biophys., 2016, 596, 22-42.
[http://dx.doi.org/10.1016/j.abb.2016.02.027] [PMID: 26926258]
[34]
Shaikh, J.; Ankola, D.D.; Beniwal, V.; Singh, D.; Kumar, M.N. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur. J. Pharm. Sci., 2009, 37(3-4), 223-230.
[http://dx.doi.org/10.1016/j.ejps.2009.02.019] [PMID: 19491009]
[35]
Jyothi, J.; Lakshmi, M.R. Pharmacodynamic activity of curcumin gels produced from curcumin solid lipid nanoparticles for rheumatoid arthritis. Int. Res. J. Pharm, 2017, 8(5), 88-94.
[http://dx.doi.org/10.7897/2230-8407.08580]
[36]
Ghaffari, S.; Alihosseini, F.; Rezayat Sorkhabadi, S.M.; Arbabi Bidgoli, S.; Mousavi, S.E.; Haghighat, S.; Afshar Nasab, A.; Kianvash, N. Nanotechnology in wound healing; semisolid dosage forms containing curcumin-ampicillin solid lipid nanoparticles, in vitro, ex vivo and in vivo characteristics. Adv. Pharm. Bull., 2018, 8(3), 395-400.
[http://dx.doi.org/10.15171/apb.2018.046] [PMID: 30276135]
[37]
Agrawal, R.; Sandhu, S.K.; Sharma, I.; Kaur, I.P. Development and evaluation of curcumin-loaded elastic vesicles as an effective topical anti-inflammatory formulation. AAPS PharmSciTech, 2015, 16(2), 364-374.
[http://dx.doi.org/10.1208/s12249-014-0232-6] [PMID: 25319056]
[38]
Noack, A.; Oidtmann, J.; Kutza, J. In vitro digestion of curcuminoid-loaded lipid nanoparticles. J. Nanopart. Res., 2012, 14, 1113.
[http://dx.doi.org/10.1007/s11051-012-1113-0]
[39]
Rramaswamy, R.; Mani, G.; Venkatachalam, S.; Venkata Yasam, R.; Rajendran, J.C.B.; Hyun Tae, J. Preparation and characterization of tetrahydrocurcumin-loaded cellulose acetate phthalate/polyethylene glycol electrospun nanofibers. AAPS PharmSciTech, 2018, 19(7), 3000-3008.
[http://dx.doi.org/10.1208/s12249-018-1122-0] [PMID: 30047034]
[40]
Tang, X.; Dong, Q.; Li, J.; Li, F.; Michniak-Kohn, B.B.; Zhao, D.; Ho, C.T.; Huang, Q. Anti-melanogenic mechanism of tetrahydrocurcumin and enhancing its topical delivery efficacy using a lecithin-based nanoemulsion. Pharmaceutics, 2021, 13(8), 1185.
[http://dx.doi.org/10.3390/pharmaceutics13081185] [PMID: 34452146]
[41]
Trivedi, M.K.; Panda, P.; Sethi, K.K.; Gangwar, M.; Mondal, S.C.; Jana, S. Solid and liquid state characterization of tetrahydrocurcumin using XRPD, FT-IR, DSC, TGA, LC-MS, GC-MS, and NMR and its biological activities. J. Pharm. Anal., 2020, 10(4), 334-345.
[http://dx.doi.org/10.1016/j.jpha.2020.02.005] [PMID: 32923007]

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