TOPICAL FORMULATION CONSTITUTED WITH TRANSFEROSOMES FOR THE TREATMENT OF NON-MELANOMA SKIN CANCER

SYED SAIF IMAM

doi:10.22159/ajpcr.2023.v16i5.47033

Authors

SYED SAIF IMAM Department of Pharmaceutical Sciences, HIMT College of Pharmacy, Greater Noida, Uttar Pradesh, India. https://orcid.org/0000-0002-0673-5898

DOI:

https://doi.org/10.22159/ajpcr.2023.v16i5.47033

Keywords:

Non-melanoma skin cancer, Curcumin, Kaempferol, Trans-resveratrol, Apigenin, Transferosomes

Abstract

Overexposure to UV-B radiation causes an evolution in the strands of DNA of skin membrane cells, resulting in non-melanoma skin cancer. With the addition of excipients and nanovesicular structures such as transferosomes that boost the permeability rate and pharmacological activity, a formulation containing curcumin, kaempferol, trans-resveratrol, and apigenin have been developed which possess strong anti-inflammatory and anti-proliferative potential. The formulation quickly penetrates the stratum corneum and acts on cancer cells, inhibiting metastasis and angiogenesis by interfering with signaling molecules in the three primary mitogen-activated protein kinase pathways: extracellular-signal-regulated kinase, c-Jun N-terminal kinases, and p38. It blocks pro-inflammatory cytokines such as lipopolysaccharide, tumor necrosis factor-alpha, IL1, IL6, COX-2, LOX, oxidative stress, and lowers the levels of matrix metalloproteinase (MMP)-3, MMP-9, and vascular endothelial growth factor. The yield value, sensory testing, spreadibility, dynamic viscosity, water content, pH, specific gravity, anti-microbial preservative concentration, microbiological limit, sterility testing, contaminants, uniformity of dosage, and assay on RAW264.7 cell line will all be used to evaluate the formulation. The O/W cream that has been produced will be significantly more successful than traditional cancer treatments, and it will have no side effects, protects the patient from recurrence of cancer and inexpensive treatment.

Downloads

Download data is not yet available.

References

Pols JC. Epidemiology of basal cell and squamous cell carcinoma of the skin. In: Skin Cancer-À World-Wide Perspective. Berlin, Heidelberg: Springer; 2010. p. 3-12.

Jeffes EW, Tang EH. Actinic keratosis. Current treatment options. Am J Clin Dermatol 2000;1:167-79. doi: 10.2165/00128071-200001030- 00004, PMID 11702298

Lober BA, Lober CW, Accola J. Actinic keratosis is squamous cell carcinoma. J Am Acad Dermatol 2000;43(5 Pt 1):881-2. doi: 10.1067/ mjd.2000.108373, PMID 11050603

Vasconcelos L, Melo JC, Miot HA, Marques ME, Abbade LP. Invasive head and neck cutaneous squamous cell carcinoma: Clinical and histopathological characteristics, frequency of local recurrence and metastasis. An Bras Dermatol 2014;89:562-8. doi: 10.1590/abd1806- 4841.20142810, PMID 25054741

Kallini JR, Hamed N, Khachemoune A. Squamous cell carcinoma of the skin: Epidemiology, classification, management, and novel trends. Int J Dermatol 2015;54:130-40. doi: 10.1111/ijd.12553, PMID 25428226

Trodello C, Pepper JP, Wong M, Wysong A. Cisplatin and cetuximab treatment for metastatic cutaneous squamous cell carcinoma: A systematic review. Dermatol Surg 2017;43:40-9. doi: 10.1097/ DSS.0000000000000799, PMID 27618393

Kazem A, Sare H, Seilanian TM, Saeede A. Nonmelanoma skin cancers: A retrospective study in department of radiation oncology, Mashhad, Iran. Iran J Dermatol 2014;17:27-30.

Didona D, Paolino G, Bottoni U, Cantisani C. Non melanoma skin cancer pathogenesis overview. Biomedicines 2018;6:6. doi: 10.3390/ biomedicines6010006, PMID 29301290

Lansbury L, Bath-Hextall F, Perkins W, Stanton W, Leonardi-Bee J. Interventions for non-metastatic squamous cell carcinoma of the skin: Systematic review and pooled analysis of observational studies. BMJ 2013;347:f6153. doi: 10.1136/bmj.f6153, PMID 24191270

Hani U, Shivakumar HG. Solubility enhancement and delivery systems of curcumin a herbal medicine: A review. Curr Drug Deliv 2014;11:792- 804. doi: 10.2174/1567201811666140825130003, PMID 25176028

Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee RK. Turmeric and curcumin: Biological actions and medicinal applications. Curr Sci 2004;87:44-53.

Shanmugam MK, Rane G, Kanchi MM, Arfuso F, Chinnathambi A, Zayed ME, et al. The multifaceted role of curcumin in cancer prevention and treatment. Molecules 2015;20:2728-69. doi: 10.3390/ molecules20022728, PMID 25665066

Singh AK, Vinayak M. Curcumin attenuates CFA induced thermal hyperalgesia by modulation of antioxidant enzymes and down regulation of TNF-α, IL-1β and IL-6. Neurochem Res 2015;40:463-72. doi: 10.1007/s11064-014-1489-6, PMID 25479948

Li ZX, Ouyang KQ, Jiang X, Wang D, Hu Y. Curcumin induces apoptosis and inhibits growth of human Burkitt’s lymphoma in xenograft mouse model. Mol Cells 2009;27:283-9. doi: 10.1007/s10059-009-0036-9, PMID 19326074

Giordano A, Tommonaro G. Curcumin and cancer. Nutrients 2019;11:2376. doi: 10.3390/nu11102376, PMID 31590362

Imran M, Salehi B, Sharifi-Rad J, Gondal TA, Saeed F, Imran A, et al. Kaempferol: A key emphasis to its anticancer potential. Molecules 2019;24:2277. doi: 10.3390/molecules24122277, PMID 31248102

Calderon-Montano MJ, Burgos-Morón E, Pérez-Guerrero C, López- Lázaro M. A review on the dietary flavonoid kaempferol. Mini Rev Med Chem 2011;11:298-344.

Park SE, Sapkota K, Kim S, Kim H, Kim SJ. Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells. Br J Pharmacol 2011;164:1008-25. doi: 10.1111/j.1476-5381.2011.01389.x, PMID 21449918

Liang SQ, Marti TM, Dorn P, Froment L, Hall SR, Berezowska S, et al. Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer. Cell Death Dis 2015;6:e1824. doi: 10.1038/cddis.2015.195, PMID 26181204

Lee KM, Lee KW, Jung SK, Lee EJ, Heo YS, Bode AM, et al. Kaempferol inhibits UVB-induced COX-2 expression by suppressing SRC kinase activity. Biochem Pharmacol 2010;80:2042-9. doi: 10.1016/j.bcp.2010.06.042, PMID 20599768

Salehi B, Mishra AP, Nigam M, Sener B, Kilic M, Sharifi-Rad M, et al. Resveratrol: A double-edged sword in health benefits. Biomedicines 2018;6:91. doi: 10.3390/biomedicines6030091, PMID 30205595

Gianchecchi E, Fierabracci A. Insights on the effects of resveratrol and some of its derivatives in cancer and autoimmunity: A molecule with a dual activity. Antioxidants (Basel) 2020;9:91. doi: 10.3390/ antiox9020091, PMID 31978952

Ko JH, Sethi G, Um JY, Shanmugam MK, Arfuso F, Kumar AP, et al. The role of resveratrol in cancer therapy. Int J Mol Sci 2017;18:2589. doi: 10.3390/ijms18122589, PMID 29194365

Khanduja KL, Bhardwaj A, Kaushik G. Resveratrol inhibits N-nitrosodiethylamine-induced ornithine decarboxylase and cyclooxygenase in mice. J Nutr Sci Vitaminol (Tokyo) 2004;50:61-5. doi: 10.3177/jnsv.50.61, PMID 15228220

Athar M, Back JH, Kopelovich L, Bickers DR, Kim AL. Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms. Arch Biochem Biophys 2009;486:95-102. doi: 10.1016/j.abb.2009.01.018, PMID 19514131

Chang CC, Chang CY, Huang JP, Hung LM. Effect of resveratrol on oxidative and inflammatory stress in liver and spleen of streptozotocin-induced Type 1 diabetic rats. Chin J Physiol 2012;55:192-201. doi: 10.4077/CJP.2012.BAA012, PMID 22784284

Kim JK, Park SU. Recent insights into the biological functions of apigenin. Excli J 2020;19:984-91. doi: 10.17179/excli2020-2579, PMID 32788912

Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, et al. The therapeutic potential of apigenin. Int J Mol Sci 2019;20:1305. doi: 10.3390/ijms20061305, PMID 30875872

Shukla S, Fu P, Gupta S. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer. Apoptosi. 2014;19:883-94. doi: 10.1007/s10495-014-0971-6, PMID 24563225

Tong X, Pelling CJ. Targeting the PI3K/Akt/mTOR axis by apigenin for cancer prevention. Anticancer Agents Med Chem 2013;13:971-8.

Shukla S, Shankar E, Fu P, MacLennan GT, Gupta S. Suppression of NF-κB and NF-κB-regulated gene expression by apigenin through IκBα and IKK pathway in TRAMP mice. PLoS One 2015;10:e0138710. doi: 10.1371/journal.pone.0138710, PMID 26379052

Lim W, Park S, Bazer FW, Song G. Apigenin reduces survival of choriocarcinoma cells by inducing apoptosis via the PI3K/AKT and ERK1/2 MAPK pathways. J Cell Physiol 2016;231:2690-9. doi: 10.1002/jcp.25372, PMID 26970256

Rezai-Zadeh K, Ehrhart J, Bai Y, Sanberg PR, Bickford P, Tan J, et al. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J Neuroinflammation 2008;5:41. doi: 10.1186/1742-2094-5-41, PMID 18817573

Opatha SA, Titapiwatanakun V, Chutoprapat R. Transfersomes: A promising nanoencapsulation technique for transdermal drug delivery. Pharmaceutics 2020;12:855. doi: 10.3390/pharmaceutics12090855, PMID 32916782

Lee MH, Thomas JL, Wang HY, Chang CC, Lin CC, Lin HY. Extraction of resveratrol from Polygonum cuspidatum with magnetic orcinol-imprinted poly (ethylene-co-vinyl alcohol) composite particles and their in vitro suppression of human osteogenic sarcoma (HOS) cell line. J Mater Chem 2012;22:24644-51. doi: 10.1039/c2jm34244h

Cid-Ortega S, Monroy-Rivera JA. Extraction of kaempferol and its glycosides using supercritical fluids from plant sources: A review. Food Technol Biotechnol 2018;56:480-93. doi: 10.17113/ftb.56.04.18.5870, PMID 30923445

Patil SS, Bhasarkar S, Rathod VK. Extraction of curcuminoids from Curcuma longa: Comparative study between batch extraction and novel three phase partitioning. Prep Biochem Biotechnol 2019;49:407-18. doi: 10.1080/10826068.2019.1575859, PMID 30821198

Liu J, Yang D, Minemoto Y, Leitges M, Rosner MR, Lin A. NF-κB is required for UV-induced JNK activation via induction of PKCδ. Mol Cell 2006;21:467-80. doi: 10.1016/j. molcel.2005.12.020, PMID 16483929

Kang OH, Lee GH, Choi HJ, Park PS, Chae HS, Jeong SI, et al. Ethyl acetate extract from Angelica dahuricae radix inhibits lipopolysaccharide-induced production of nitric oxide, prostaglandin E2 and tumor necrosis factor-α via mitogen-activated protein kinases and nuclear factor-κB in macrophages. Pharmacol Res 2007;55:263-70. doi: 10.1016/j.phrs.2006.12.001, PMID 17229575

Schiechl G, Bauer B, Fuss I, Lang SA, Moser C, Ruemmele P, et al. Tumor development in murine ulcerative colitis depends on MyD88 signaling of colonic. F4/80+CD11b high Gr1 low macrophages. J Clin Invest 2011;121:1692-708.

Bose S, Kim H. Evaluation of in vitro anti-inflammatory activities and protective effect of fermented preparations of rhizoma Atractylodes macrocephalae on intestinal barrier function against lipopolysaccharide insult. Evid Based Complement Alternat Med 2013;2013:363076. doi: 10.1155/2013/363076

Imam SS, Agarwal S. A pragmatic approach to treat lung cancer through loading theaflavin-3,3-digallate and epigallocatechin gallate in Spanlastic. Asian J Pharm Clin Res 2021;14:1-8. doi: 10.22159/ ajpcr.2021.v14i11.42757

De Oliveira Júnior RG, Ferraz CA, Silva MG, de Lavor ÉM, Rolim LA, de Lima JT, et al. Flavonoids: Promising natural products for treatment of skin cancer (melanoma). In: Badria FA, editor. Natural Products and Cancer Drug Discovery. Rijeka, Croatia: Intech Open; 2017. p. 161-210.

Chinembiri TN, Du Plessis LH, Gerber M, Hamman JH, Du Plessis J. Review of natural compounds for potential skin cancer treatment. Molecules 2014;19:11679-721. doi: 10.3390/molecules190811679, PMID 25102117

Cullen JK, Simmons JL, Parsons PG, Boyle GM. Topical treatments for skin cancer. Adv Drug Deliv Rev 2020;153:54-64. doi: 10.1016/j. addr.2019.11.002, PMID 31705912

García-Bores AM, Avila JG. Natural products: Molecular mechanisms in the photochemo prevention of skin cancer. Rev Latinoamer Quím 2008;36:83-102.

Sajadimajd S, Bahramsoltani R, Iranpanah A, Patra JK, Das G, Gouda S, et al. Advances on natural polyphenols as anticancer agents for skin cancer. Pharmacol Res 2020;151:104584. doi: 10.1016/j. phrs.2019.104584, PMID 31809853

Chamcheu JC, Roy T, Uddin MB, Banang-Mbeumi S, Chamcheu RN, Walker AL, et al. Role and therapeutic targeting of the PI3K/Akt/ mTORsignaling pathway in skin cancer: A review of current status and future trends on natural and synthetic agents therapy. Cells 2019;8:803. doi: 10.3390/cells8080803, PMID 31370278

Iqubal MK, Chaudhuri A, Iqubal A, Saleem S, Gupta MM, Ahuja A, et al. Targeted delivery of natural bioactives and lipid-nanocargos against signaling pathways involved in skin cancer. Curr Med Chem 2021;28:8003-35. doi: 10.2174/0929867327666201104151752, PMID 33148148

Pavithra PS, Mehta A, Verma RS. Essential oils: From prevention to treatment of skin cancer. Drug Discov Today 2019;24:644-55. doi: 10.1016/j.drudis.2018.11.020, PMID 30508640

Konoshima T, Kozuka M, Tokuda H, Nishino H, Iwashima A, Haruna M, et al. Studies on inhibitors of skin tumor promotion, IX. Neolignans from Magnolia officinalis. J Nat Prod 1991;54:816-22. doi: 10.1021/np50075a010, PMID 1659613

Marrelli M, Menichini G, Provenzano E, Conforti F. Applications of natural compounds in the photodynamic therapy of skin cancer. Curr Med Chem 2014;21:1371-90. doi: 10.2174/092986732112140319 094324, PMID 23531223

Cham BE. Solasodine rhamnosyl glycosides specifically bind cancer cell receptors and induce apoptosis and necrosis. Treatment for skin cancer and hope for internal cancers. Res J Biol Sci 2007;2:503-14.

Nazir S, Khan MU, Al-Arjan WS, Abd Razak SI, Javed A, Kadir MR. Nanocomposite hydrogels for melanoma skin cancer care and treatment: In-vitro drug delivery, drug release kinetics and anti-cancer activities. Arab J Chem 2021;14:103120. doi: 10.1016/j. arabjc.2021.103120