FORMULATION OPTIMIZATION, CHARACTERIZATION AND IN VITRO ANTI-CANCER ACTIVITY OF CURCUMIN LOADED NANOSTRUCTURED LIPID CARRIERS

JINAL SHAH; SHOAIB PATEL; SRINIVAS BHAIRY; RAJASHREE HIRLEKAR

doi:10.22159/ijcpr.2022v14i1.44110

Authors

JINAL SHAH Department of Pharmaceutics, Vivekanand Education Society’s College of Pharmacy (Affiliated to University of Mumbai), Hashu Advani Memorial Complex, Behind Collector Colony, Chembur (E), Mumbai 400074, Maharashtra, India
SHOAIB PATEL Department of Pharmaceutics, Vivekanand Education Society’s College of Pharmacy (Affiliated to University of Mumbai), Hashu Advani Memorial Complex, Behind Collector Colony, Chembur (E), Mumbai 400074, Maharashtra, India
SRINIVAS BHAIRY Department of Pharmaceutics, Vivekanand Education Society’s College of Pharmacy (Affiliated to University of Mumbai), Hashu Advani Memorial Complex, Behind Collector Colony, Chembur (E), Mumbai 400074, Maharashtra, India
RAJASHREE HIRLEKAR Department of Pharmaceutics, Vivekanand Education Society’s College of Pharmacy (Affiliated to University of Mumbai), Hashu Advani Memorial Complex, Behind Collector Colony, Chembur (E), Mumbai 400074, Maharashtra, India

DOI:

https://doi.org/10.22159/ijcpr.2022v14i1.44110

Keywords:

Curcumin, Nanostructured lipid carrier, Lyophilization, Anti-cancer activity

Abstract

Objective: The present study was aimed at preparing stable lyophilized curcumin loaded nanostructured lipid carriers (NLCs). The optimized lyophilized curcumin loaded NLCs were characterized and evaluated for various quality control parameters.

Methods: The optimized curcumin loaded NLCs were prepared by modified hot emulsification using precirol ATO 5 (PRE), capmul MCM C8 EP (CAP) as solid and liquid lipids, respectively. The combination of tween 80 (T80) and solutol HS 15 (SHS) were used as an emulsifier. The NLCs dispersion was lyophilized into powder form to improve the thermodynamic stability of the formulation. The lyophilized curcumin loaded NLCs were evaluated for particle size, size distribution, zeta potential, entrapment efficiency (EE), drug loading, assay, in vitro drug release, crystallinity and surface morphology studies.

Results: The optimized lyophilized curcumin loaded NLCs have a mean particle size of 286.2±11.5 nm with a size distribution of 0.288±0.011, a zeta potential of 0.247±0.025 mV with high entrapment of 98.20±1.53 % and drug loading of 2.50±0.21 %. The X-ray diffraction and endothermic peaks confirmed the maximum encapsulation of curcumin in lipid matrices. The particles were spherical with smooth surface morphology. In vitro release studies showed sustained release for up to 24 h. The cytotoxicity against human lung cancer line A-549 for curcumin-loaded NLCs was confirmed with positive control adriamycin (ADR).

Conclusion: Curcumin-loaded NLCs prepared had a nanosize particle distribution with maximum entrapment efficiency. Dispersion stability was increased by the lyophilisation process. The solid lyophilized powder is reconstituted for oral delivery.

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References

Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013;15(1):195-218. doi: 10.1208/s12248-012-9432-8, PMID 23143785.

Allegra A, Innao V, Russo S, Gerace D, Alonci A, Musolino C. Anticancer activity of curcumin and its analogues: preclinical and clinical studies. Cancer Invest. 2017;35(1):1-22. doi: 10.1080/07357907.2016.1247166, PMID 27996308.

Shanmugam MK, Rane G, Kanchi MM, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, Tan BK, Kumar AP, Sethi G. The multifaceted role of curcumin in cancer prevention and treatment. Molecules. 2015;20(2):2728-69. doi: 10.3390/ molecules20022728, PMID 25665066.

Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini KI. Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochim Biophys Acta. 2008;1780(4):673-9. doi: 10.1016/ j.bbagen. 2007.11.016, PMID 18178166.

Syng-Ai C, Kumari AL, Khar A. Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Mol Cancer Ther. 2004;3(9):1101-8. PMID 15367704.

Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11(3):495-510. doi: 10.1208/s12248-009-9128-x, PMID 19590964.

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. doi: 10.1055/s-2006-957450, PMID 9619120.

Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol. 2007;595:453-70. doi: 10.1007/978-0-387-46401-5_20, PMID 17569224.

Shen L, Ji HF. The pharmacology of curcumin: is it the degradation products? Trends Mol Med. 2012;18(3):138-44. doi: 10.1016/j.molmed.2012.01.004, PMID 22386732.

Ghorpade K, Shinde S. Design and development of curcumin loaded nanostructured lipid carriers for solubility enhancement. Int J Curr Res. 2019;11(1):20-6.

Sadati Behbahani ES, Ghaedi M, Abbaspour M, Rostamizadeh K, Dashtian K. Curcumin loaded nanostructured lipid carriers: in vitro digestion and release studies. Polyhedron. 2019;164:113-22. doi: 10.1016/j.poly.2019.02.002.

Fang M, Jin Y, Bao W, Gao H, Xu M, Wang D, Wang X, Yao P, Liu L. In vitro characterization and in vivo evaluation of nanostructured lipid curcumin carriers for intragastric administration. Int J Nanomedicine. 2012;7:5395-404. doi: 10.2147/IJN.S36257, PMID 23091382.

Chen P, Zhang H, Cheng S, Zhai G, Shen C. Development of curcumin loaded nanostructured lipid carrier based thermosensitive in situ gel for dermal delivery. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2016;506:356-62. doi: 10.1016/j.colsurfa.2016.06.054.

Rapalli VK, Kaul V, Waghule T, Gorantla S, Sharma S, Roy A, Dubey SK, Singhvi G. Curcumin loaded nanostructured lipid carriers for enhanced skin retained topical delivery: optimization, scale-up, in-vitro characterization and assessment of ex-vivo skin deposition. Eur J Pharm Sci. 2020;152:105438. doi: 10.1016/j.ejps.2020.105438, PMID 32598913.

Esposito E, Ravani L, Mariani P, Huang N, Boldrini P, Drechsler M, Valacchi G, Cortesi R, Puglia C. Effect of nanostructured lipid vehicles on percutaneous absorption of curcumin. Eur J Pharm Biopharm. 2014;86(2):121-32. doi: 10.1016/j.ejpb. 2013. 12.011, PMID 24361485.

Lee HJ, Jeong M, Na YG, Kim SJ, Lee HK, Cho CW. An EGF- and curcumin-co-encapsulated nanostructured lipid carrier accelerates chronic-wound healing in diabetic rats. Molecules. 2020;25(20):1-14. doi: 10.3390/molecules25204610, PMID 33050393.

Rabima R, Oktamauri A. Characterization and antibacterial activity of curcumin-nanostructured lipid carrier. Indones Nat Res Pharm J 2019;3(2):1-10.

Sadegh Malvajerd S, Izadi Z, Azadi A, Kurd M, Derakhshankhah H, Sharifzadeh M, Akbari Javar H, Hamidi M. Neuroprotective potential of curcumin-loaded nanostructured lipid carrier in an animal model of Alzheimer’s disease: behavioral and biochemical evidence. J Alzheimers Dis. 2019;69(3):671-86. doi: 10.3233/JAD-190083, PMID 31156160.

Lakhani P, Patil A, Taskar P, Ashour E, Majumdar S. Curcumin-loaded nanostructured lipid carriers for ocular drug delivery: design optimization and characterization. J Drug Deliv Sci Technol. 2018;47:159-66. doi: 10.1016/j.jddst.2018.07.010, PMID 32601526.

Yoozbashi M, Rashidzadeh H, Kermanian M, Sadighian S, Hosseini M, Kaboli Z, Rostamizadeh K. Magnetic nanostructured lipid carrier for dual triggered curcumin delivery: Preparation, characterization and toxicity evaluation on isolated rat liver mitochondria. J Biomater Appl. 2021 Jul;28: 8853282211034625. doi: 10.1177/ 08853282211034625.

Meng F, Asghar S, Xu Y, Wang J, Jin X, Wang Z, Wang J, Ping Q, Zhou J, Xiao Y. Design and evaluation of lipoprotein resembling curcumin-encapsulated protein-free nanostructured lipid carrier for brain targeting. Int J Pharm. 2016;506(1-2):46-56. doi: 10.1016/j.ijpharm.2016.04.033, PMID 27094357.

Wang F, Ye X, Zhai D, Dai W, Wu Y, Chen J, Chen W. Curcumin-loaded nanostructured lipid carrier induced apoptosis in human HepG2 cells through activation of the DR5/caspase-mediated extrinsic apoptosis pathway. Acta Pharm. 2020;70(2):227-37. doi: 10.2478/acph-2020-0003, PMID 31955141.

Madane RG, Mahajan HS. Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study. Drug Deliv. 2016;23(4):1326-34. doi: 10.3109/10717544.2014.975382, PMID 25367836.

Chanburee S, Tiyaboonchai W. Enhanced intestinal absorption of curcumin in Caco-2 cell monolayer using mucoadhesive nanostructured lipid carriers. J Biomed Mater Res B Appl Biomater. 2018;106(2):734-41. doi: 10.1002/jbm.b.33884, PMID 28323388.

Chen Y, Pan L, Jiang M, Li D, Jin L. Nanostructured lipid carriers enhance the bioavailability and brain cancer inhibitory efficacy of curcumin both in vitro and in vivo. Drug Deliv. 2016;23(4):1383-92. doi: 10.3109/10717544.2015.1049719, PMID 26066035.

Kamel AE, Fadel M, Louis D. Curcumin-loaded nanostructured lipid carriers prepared using Peceol™ and olive oil in photodynamic therapy: development and application in breast cancer cell line. Int J Nanomedicine. 2019;14:5073-85. doi: 10.2147/IJN.S210484, PMID 31371948.

Rabima OA, Oktamauri A. Characterisation and cytotoxicity assay of curcumin nanostructured lipid carrier on HeLa cells. IOP Conf Ser: Earth Environ Sci. 2021;667(1):1-8. doi: 10.1088/1755-1315/667/1/012055.

Wang F, Chen J, Dai W, He Z, Zhai D, Chen W. Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers. Acta Pharm. 2017;67(3):357-71. doi: 10.1515/acph-2017-0021, PMID 28858837.

Arora R, Katiyar SS, Kushwah V, Jain S. Solid lipid nanoparticles and nanostructured lipid carrier-based nanotherapeutics in treatment of psoriasis: a comparative study. Expert Opin Drug Deliv. 2017;14(2):165-77. doi: 10.1080/17425247.2017.1264386, PMID 27882780.

Jain S, Cherukupalli SK, Mahmood A, Gotantla S, Rapalli VK, Dubey SK. Emerging nanoparticulate systems: preparation techniques and stimuli responsive release characteristics. J App Pharm Sci. 2019;9(8):130-43. doi: 10.7324/JAPS.2019.90817.

Sonawane R, Harde H, Katariya M, Agrawal S, Jain S. Solid lipid nanoparticles-loaded topical gel containing combination drugs: an approach to offset psoriasis. Expert Opin Drug Deliv. 2014;11(12):1833-47. doi: 10.1517/17425247.2014.938634, PMID 25078031.

Panigrahi S, Hirlekar R. A new stability-indicating RP-HPLC method for determination of curcumin: an application to nanoparticulate formulation. Int J Pharm Pharm Sci. 2016;8(12):149-55. doi: 10.22159/ijpps.2016v8i12.14473.

Padhye SG, Nagarsenker MS. Simvastatin solid lipid nanoparticles for oral delivery: formulation development and in vivo evaluation. Indian J Pharm Sci. 2013;75(5):591-8. PMID 24403661.

Westesen K, Bunjes H, Koch MHJ. Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential. J Control Release. 1997;48(2-3):223-36. doi: 10.1016/S0168-3659(97)00046-1.

Aungst BJ. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J Pharm Sci. 1993;82(10):979-87. doi: 10.1002/jps.2600821008, PMID 8254497.

Maryam BZ, Akram P. Effect of surfactant concentration on the particle size, stability and potential zeta of beta carotene Nano lipid carrier. Int J Curr Microbiol Appl Sci. 2015;4(9):924-32.

Helgason T, Awad TS, Kristbergsson K, McClements DJ, Weiss J. Effect of surfactant surface coverage on formation of solid lipid nanoparticles (SLN). J Colloid Interface Sci. 2009;334(1):75-81. doi: 10.1016/j.jcis.2009.03.012, PMID 19380149.

Kovacevic A, Savic S, Vuleta G, Muller RH, Keck CM. Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure. Int J Pharm. 2011;406(1-2):163-72. doi: 10.1016/j.ijpharm.2010.12.036, PMID 21219990.

Wolfgang M, Karsten M. Solid lipid nanoparticles production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2):165-96.

Silva AC, González-Mira E, García ML, Egea MA, Fonseca J, Silva R, Santos D, Souto EB, Ferreira D. Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): high pressure homogenization versus ultrasound. Colloids Surf B Biointerfaces. 2011;86(1):158-65. doi: 10.1016/j.colsurfb.2011.03.035, PMID 21530187.

Amis TM, Renukuntla J, Bolla PK, Clark BA. Selection of cryoprotectant in lyophilization of progesterone-loaded stearic acid solid lipid nanoparticles. Pharmaceutics. 2020;12(9):1-15. doi: 10.3390/pharmaceutics12090892, PMID 32961738.

Hu FX, Neoh KG, Kang ET. Synthesis and in vitro anti-cancer evaluation of tamoxifen-loaded magnetite/PLLA composite nanoparticles. Biomaterials. 2006;27(33):5725-33. doi: 10.1016/j.biomaterials.2006.07.014, PMID 16890989.