Design and Evaluation of SLNs Encapsulated Curcumin-based Topical Formulation for the Management of Cervical Cancer
- Authors: Singhai M.1, Pandey V.2, Ashique S.3, Gupta G.1, Arora D.4, Haider T.2, Mishra N.2
-
Affiliations:
- Department of Pharmaceutics, ISF College of Pharmacy
- Amity Institute of Pharmacy, Amity University Madhya Pradesh
- Department of Pharmaceutics, Pandaveswar School of Pharmacy
- Department of Pharmacy, Panipat Institute of Technology and Sciences
- Issue: Vol 23, No 16 (2023)
- Pages: 1866-1879
- Section: Oncology
- URL: https://kld-journal.fedlab.ru/1871-5206/article/view/694360
- DOI: https://doi.org/10.2174/1871520623666230626145750
- ID: 694360
Cite item
Full Text
Abstract
Objective: Curcumin has the propensity to inhibit cancer growth, slow cancer development, increase chemotherapy effectiveness, and shield healthy cells from radiation treatment harm. As a result of curcumin's ability to block several signaling pathways, cervical cancer cells can once again proliferate normally. To optimize topically applied curcumin-loaded solid lipid nanoparticles (SLNPs) for the treatment of cervical cancer, this study set out to establish the relationship between design variables and experimental data. It also performed in vitro characterizations to determine the formulation's efficacy and safety.
Methods: Curcumin-loaded SLNPs were constructed and optimized using a systematic design of experiment (DoE) technique. SLNPs that were loaded with curcumin were produced utilizing a cold emulsification ultrasonication process. Using the Box Behnken Design, it was determined how independent variables (factors) like the quantity of lipid (A), the quantity of phospholipid (B), and the concentration of surfactant (C) affected the responses of the dependent variables (responses), such as particle size (Y1), polydispersity index (PDI) (Y2), and entrapment efficiency (EE) (Y3) (BBD).
Results: The ideal formulation (SLN9) was chosen using the desirability technique based on 3-D surface response graphs. Using polynomial equations and three-dimensional surface plots, the influence of independent factors on the dependent variables was evaluated. The observed responses were almost equal to the levels that the optimal formulation expected. The improved SLNP gel's shape and other physicochemical characteristics were also assessed, and they were determined to be ideal. The sustained release profile of the produced formulations was validated by in vitro release tests. Studies on hemolysis, immunogenic response, and in vitro cell cytotoxicity demonstrate the efficacy and safety of the formulations.
Conclusion: To improve the treatment effect, chitosan-coated SLNPs may carry encapsulated curcumin to the desired location and facilitate its localization and deposition in the desired vaginal tissue.
About the authors
Manu Singhai
Department of Pharmaceutics, ISF College of Pharmacy
Email: info@benthamscience.net
Vikas Pandey
Amity Institute of Pharmacy, Amity University Madhya Pradesh
Email: info@benthamscience.net
Sumel Ashique
Department of Pharmaceutics, Pandaveswar School of Pharmacy
Email: info@benthamscience.net
Ghanshyam Gupta
Department of Pharmaceutics, ISF College of Pharmacy
Email: info@benthamscience.net
Daisy Arora
Department of Pharmacy, Panipat Institute of Technology and Sciences
Email: info@benthamscience.net
Tanweer Haider
Amity Institute of Pharmacy, Amity University Madhya Pradesh
Email: info@benthamscience.net
Neeraj Mishra
Amity Institute of Pharmacy, Amity University Madhya Pradesh
Author for correspondence.
Email: info@benthamscience.net
References
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424. doi: 10.3322/caac.21492 PMID: 30207593
- Rama, S.; Fauziya, H.; Nisha, T.; Manu, S.; Akhlesh, K.S.; Laxmi, T. Recent advancements in development of vaccines for the treatment of cancer: A review. Int. J. Pharma Sci., 2019, 5(2), 55-60.
- Smith, R.A.; Andrews, K.S.; Brooks, D.; Fedewa, S.A.; Manassaram-Baptiste, D.; Saslow, D.; Brawley, O.W.; Wender, R.C. Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J. Clin., 2018, 68(4), 297-316. doi: 10.3322/caac.21446 PMID: 29846940
- Pimple, S.; Mishra, G.; Shastri, S. Global strategies for cervical cancer prevention. Curr. Opin. Obstet. Gynecol., 2016, 28(1), 4-10. doi: 10.1097/GCO.0000000000000241 PMID: 26642063
- Goodarzi, E.; Khazaei, Z.; Sohrabivafa, M.; Mansori, K.; Naemi, H. Incidence and mortality of cervix cancer and their relationship with the human development index in 185 countries in the world: An ecology study in 2018. Adv. Hum. Biol., 2019, 9(3), 222. doi: 10.4103/AIHB.AIHB_15_19
- Apostolopoulos, V. Cancer vaccines: Research and applications. Cancers (Basel), 2019, 11(8), 1041. doi: 10.3390/cancers11081041 PMID: 31344788
- Singh, A.; Negi, D. kaur, S.; Bhattachary, S.; Singh, G. Fundamentals of nanocarriers and probiotics in the treatment of cervical cancer. Curr. Nanomed., 2020, 10(4), 342-357. doi: 10.2174/2468187310999201105143429
- Din, F.; Aman, W.; Ullah, I.; Qureshi, O.S.; Mustapha, O.; Shafique, S.; Zeb, A. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int. J. Nanomed., 2017, 12, 7291-7309. doi: 10.2147/IJN.S146315 PMID: 29042776
- Kjaer, S.K.; Brule, A.J.C. Van Den; Paull, G; Svare, EI; Sherman, ME; Thomsen, BL; Suntum, M; Bock, JE; Poll, PA; Meijer, CJLM Type-specific persistence of high-risk human papillomavirus (HPV) as an indicator of high grade cervical squamous intraepithelial lesions in young women: Population based prospective follow up study. BMJ, 2002, 25(7364), 572. doi: 10.1136/bmj.325.7364.572 PMID: 12228133
- Varan, C.; Wickström, H.; Sandler, N. Aktaş Y.; Bilensoy, E. Inkjet printing of antiviral PCL nanoparticles and anticancer cyclodextrin inclusion complexes on bioadhesive film for cervical administration. Int. J. Pharm., 2017, 531(2), 701-713. doi: 10.1016/j.ijpharm.2017.04.036 PMID: 28432016
- Gupta, S.; Gupta, M.K. Possible role of nanocarriers in drug delivery against cervical cancer. Nano Rev. Exp., 2017, 8(1), 1335567. doi: 10.1080/20022727.2017.1335567 PMID: 30410707
- Soni, H.; Sharan, P.S.; Mishra, K.; Nayak, G.; Singhai, A.K. Qualitative and quantitative profile of curcumin from ethanolic extract of curcuma longa. Int. Res. J. Pharm., 2011, 2(4), 180-184.
- Giordano, A.; Tommonaro, G. Curcumin and cancer. Nutrients, 2019, 11(10), 2376. doi: 10.3390/nu11102376 PMID: 31590362
- Pourhanifeh, M.H.; Darvish, M.; Tabatabaeian, J.; Fard, M.R.; Mottaghi, R.; Azadchehr, M.J.; Jahanshahi, M.; Sahebkar, A.; Mirzaei, H. Therapeutic role of curcumin and its novel formulations in gynecological cancers. J. Ovarian Res., 2020, 13(1), 130. doi: 10.1186/s13048-020-00731-7 PMID: 33148295
- Zaman, M.S.; Chauhan, N.; Yallapu, M.M.; Gara, R.K.; Maher, D.M.; Kumari, S.; Sikander, M.; Khan, S.; Zafar, N.; Jaggi, M.; Chauhan, S.C. Curcumin nanoformulation for cervical cancer treatment. Sci. Rep., 2016, 6(1), 20051. doi: 10.1038/srep20051 PMID: 26837852
- Himiniuc, L.M.; Toma, B.F.; Popovici, R.; Grigore, A.M.; Hamod, A.; Volovat, C.; Volovat, S.; Nica, I.; Vasincu, D.; Agop, M.; Tirnovanu, M.; Ochiuz, L.; Negura, L.; Grigore, L. Update on the use of nanocarriers and drug delivery systems and future directions in cervical cancer. J. Immunol. Res., 2022, 2022, 1636908. doi: 10.1155/2022/1636908 PMID: 35571568
- Aqil, F.; Munagala, R.; Jeyabalan, J.; Agrawal, A.K.; Gupta, R. Exosomes for the enhanced tissue bioavailability and efficacy of curcumin. AAPS J., 2017, 19(6), 1691-1702. doi: 10.1208/s12248-017-0154-9 PMID: 29047044
- Li, R.; Deng, L.; Cai, Z.; Zhang, S.; Wang, K.; Li, L.; Ding, S.; Zhou, C. Liposomes coated with thiolated chitosan as drug carriers of curcumin. Mater. Sci. Eng. C, 2017, 80, 156-164. doi: 10.1016/j.msec.2017.05.136 PMID: 28866151
- Cheng, Y.; Zhao, P.; Wu, S.; Yang, T.; Chen, Y.; Zhang, X.; He, C.; Zheng, C.; Li, K.; Ma, X.; Xiang, G. Cisplatin and curcumin co-loaded nano-liposomes for the treatment of hepatocellular carcinoma. Int. J. Pharm., 2018, 545(1-2), 261-273. doi: 10.1016/j.ijpharm.2018.05.007 PMID: 29730175
- Tai, K.; Rappolt, M.; Mao, L.; Gao, Y.; Yuan, F. Stability and release performance of curcumin-loaded liposomes with varying content of hydrogenated phospholipids. Food Chem., 2020, 326(May), 126973. doi: 10.1016/j.foodchem.2020.126973 PMID: 32413757
- Moorthi, C.; Kathiresan, K. CurcuminPiperine/CurcuminQuercetin/CurcuminSilibinin dual drug-loaded nanoparticulate combination therapy: A novel approach to target and treat multidrug-resistant cancers. J. Med. Hypotheses Ideas, 2013, 7(1), 15-20. doi: 10.1016/j.jmhi.2012.10.005
- R David, S.; Akmar B A, N.; Yian, K.R.; Mai, C.W.; Das, S.K.; Rajabalaya, R. Development and evaluation of curcumin liquid crystal systems for cervical cancer. Sci. Pharm., 2020, 88(1), 15. doi: 10.3390/scipharm88010015
- Ramezani, F.M.; Azarian, M.; Heydari, S.H.H.; Abdolvahabi, Z.; Mohammadi, A.Z.; Moradi, A.; Mousavi, S.M.; Ashrafizadeh, M.; Makvandi, P.; Saeb, M.R.; Rabiee, N. Folic acid-adorned curcumin-loaded iron oxide nanoparticles for cervical cancer. ACS Appl. Bio Mater., 2022, 5(3), 1305-1318. doi: 10.1021/acsabm.1c01311 PMID: 35201760
- Wang, J.; Liu, Q.; Yang, L.; Xia, X.; Zhu, R.; Chen, S.; Wang, M.; Cheng, L.; Wu, X.; Wang, S. Curcumin-loaded TPGS/F127/P123 mixed polymeric micelles for cervical cancer therapy: Formulation, characterization, and in vitro and in vivo evaluation. J. Biomed. Nanotechnol., 2017, 13(12), 1631-1646. doi: 10.1166/jbn.2017.2442 PMID: 29490752
- Kumari, P.; Rompicharla, S.V.K.; Muddineti, O.S.; Ghosh, B.; Biswas, S. Transferrin-anchored poly(lactide) based micelles to improve anticancer activity of curcumin in hepatic and cervical cancer cell monolayers and 3D spheroids. Int. J. Biol. Macromol., 2018, 116, 1196-1213. doi: 10.1016/j.ijbiomac.2018.05.040 PMID: 29753013
- Wang, L.; Xu, X.; Zhang, Y.; Zhang, Y.; Zhu, Y.; Shi, J.; Sun, Y.; Huang, Q. Encapsulation of curcumin within poly(amidoamine) dendrimers for delivery to cancer cells. J. Mater. Sci. Mater. Med., 2013, 24(9), 2137-2144. doi: 10.1007/s10856-013-4969-3 PMID: 23779153
- Ghaffari, M.; Dehghan, G.; Baradaran, B.; Zarebkohan, A.; Mansoori, B.; Soleymani, J.; Ezzati, N.D.J.; Hamblin, M.R. Co-delivery of curcumin and Bcl-2 siRNA by PAMAM dendrimers for enhancement of the therapeutic efficacy in HeLa cancer cells. Colloids Surf. B Biointerfaces, 2020, 188, 110762. doi: 10.1016/j.colsurfb.2019.110762
- Gumireddy, A.; Christman, R.; Kumari, D.; Tiwari, A.; North, E.J.; Chauhan, H. Preparation, characterization, and in vitro evaluation of curcumin- and resveratrol-loaded solid lipid nanoparticles. AAPS PharmSciTech, 2019, 20(4), 145. doi: 10.1208/s12249-019-1349-4 PMID: 30887133
- Gupta, T.; Singh, J.; Kaur, S.; Sandhu, S.; Singh, G.; Kaur, I.P. Enhancing bioavailability and stability of curcumin using solid lipid nanoparticles (clen): A covenant for its effectiveness. Front. Bioeng. Biotechnol., 2020, 8, 879. doi: 10.3389/fbioe.2020.00879 PMID: 33178666
- Almeida, A.; Souto, E. Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Adv. Drug Deliv. Rev., 2007, 59(6), 478-490. doi: 10.1016/j.addr.2007.04.007 PMID: 17543416
- Wu, X.Y. Strategies for optimizing polymer-lipid hybrid nanoparticle-mediated drug delivery. Expert Opin. Drug Deliv., 2016, 13(5), 609-612. doi: 10.1517/17425247.2016.1165662 PMID: 26978527
- Wang, J.; Wang, Y.; Meng, X. Chitosan nanolayered cisplatin-loaded lipid nanoparticles for enhanced anticancer efficacy in cervical cancer. Nanoscale Res. Lett., 2016, 11(1), 524. doi: 10.1186/s11671-016-1698-9 PMID: 27888498
- Gordillo-Galeano, A.; Mora-Huertas, C.E. Solid lipid nanoparticles and nanostructured lipid carriers: A review emphasizing on particle structure and drug release. Eur. J. Pharm. Biopharm., 2018, 133(10), 285-308. doi: 10.1016/j.ejpb.2018.10.017 PMID: 30463794
- Mishra, V.; Bansal, K.; Verma, A.; Yadav, N.; Thakur, S.; Sudhakar, K.; Rosenholm, J. Solid lipid nanoparticles: Emerging colloidal nano drug delivery systems. Pharmaceutics, 2018, 10(4), 191. doi: 10.3390/pharmaceutics10040191 PMID: 30340327
- Bayón-Cordero, L.; Alkorta, I.; Arana, L. Application of solid lipid nanoparticles to improve the efficiency of anticancer drugs. Nanomaterials (Basel), 2019, 9(3), 474. doi: 10.3390/nano9030474 PMID: 30909401
- Tabatabaeain, S.F.; Karimi, E.; Hashemi, M. Satureja khuzistanica essential oil-loaded solid lipid nanoparticles modified with chitosan-folate: Evaluation of encapsulation efficiency, cytotoxic and pro-apoptotic properties. Front Chem., 2022, 10, 904973. doi: 10.3389/fchem.2022.904973 PMID: 35815210
- Arora, D.; Khurana, B.; Nanda, S. Statistical development and in vivo evaluation of resveratrol-loaded topical gel containing deformable vesicles for a significant reduction in photo-induced skin aging and oxidative stress. Drug Dev. Ind. Pharm., 2020, 46(11), 1898-1910. a doi: 10.1080/03639045.2020.1826507 PMID: 32962434
- Khurana, B.; Arora, D.; Narang, R.K. QbD based exploration of resveratrol loaded polymeric micelles based carbomer gel for topical treatment of plaque psoriasis: In vitro, ex vivo and in vivo studies. J. Drug Deliv. Sci. Technol., 2020, 59, 101901. doi: 10.1016/j.jddst.2020.101901
- Caramella, C.M.; Rossi, S.; Ferrari, F.; Bonferoni, M.C.; Sandri, G. Mucoadhesive and thermogelling systems for vaginal drug delivery. Adv. Drug Deliv. Rev., 2015, 92, 39-52. doi: 10.1016/j.addr.2015.02.001 PMID: 25683694
- Martínez-Pérez, B.; Quintanar-Guerrero, D.; Tapia-Tapia, M.; Cisneros-Tamayo, R.; Zambrano-Zaragoza, M.L.; Alcalá-Alcalá, S.; Mendoza-Muñoz, N.; Piñón-Segundo, E. Controlled-release biodegradable nanoparticles: From preparation to vaginal applications. Eur. J. Pharm. Sci., 2018, 115, 185-195. doi: 10.1016/j.ejps.2017.11.029 PMID: 29208486
Supplementary files
