Generic placeholder image

Current Nanomedicine

Editor-in-Chief

ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

Research Article

Preparation and Characterization of 5-Fluorouracil Loaded Nanogels for Skin Cancer Treatments: In Vitro Drug Release, Cytotoxicity and Cellular Uptake Analysis

Author(s): Swati Rathore*, Vaibhav Rajoriya, Varun Kushwaha, Sanyog Jain and Sushil K. Kashaw

Volume 11, Issue 2, 2021

Published on: 01 March, 2021

Page: [127 - 138] Pages: 12

DOI: 10.2174/2468187311666210301112644

Price: $65

Abstract

Objective: The present study aimed to explore the in-vitro anticancer potential of 5-fluorouracil (5-FU) loaded PLGA nanogels coated with nerolidol sesquiterpene.

Methods: The emulsification-solvent evaporation technique was used for the preparation of plain PLGA nanogels (PNGs) and 5-FU loaded PLGA nanogels (FPNGs). A surface coating of Nerolidol (2%) sesquiterpene was employed to improve the penetration efficacy of the nanogels into the stratum corneum.

Results: The nanogels formulation FPNGs have the size range 220±0.25% nm obtained by dynamic light scattering. The entrapment efficiency of approx ~ 42% with a sustained-release pattern for 24 h was estimated at different pH ranges. The cell uptake and localization profile were revealed by confocal microscopy analysis using the HaCaT cell line. MTT assay demonstrated the cell compatibility of nanogels, confirmed by apoptosis assay depicting the apoptotic index of 0.87.

Conclusion: This study concludes that FPNGs are a promising nanogels system against skin cancer that can be used to boost the chemo-therapeutic efficiency of bioactives with sustained and controlled release at the desired site.

Keywords: Biodegradable, polymeric nanogels, nerolidol, in-vitro, sustained release, skin cancer, controlled release.

Graphical Abstract
[1]
Whiteman DC, Green AC, Olsen CM. Growing burden of invasive melanoma: projections of incidence rates and numbers of new cases in six susceptible populations through 2031. J Invest Dermatol 2016; 136(6): 1161-71.
[http://dx.doi.org/10.1016/j.jid.2016.01.035] [PMID: 26902923]
[2]
Perera E, Gnaneswaran N, Staines C, Win AK, Sinclair R. Incidence and prevalence of non-melanoma skin cancer in Australia: A systematic review. Australas J Dermatol 2015; 56(4): 258-67.
[http://dx.doi.org/10.1111/ajd.12282] [PMID: 25716064]
[3]
Brunssen A, Waldmann A, Eisemann N, Katalinic A. Impact of skin cancer screening and secondary prevention campaigns on skin cancer incidence and mortality: A systematic review. J Am Acad Dermatol 2017; 76(1): 129-139.e10.
[http://dx.doi.org/10.1016/j.jaad.2016.07.045] [PMID: 27707591]
[4]
Esteva A, Kuprel B, Novoa RA, et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature 2017; 542(7639): 115-8.
[http://dx.doi.org/10.1038/nature21056] [PMID: 28117445]
[5]
Naves LB, Dhand C, Venugopal JR, Rajamani L, Ramakrishna S, Almeida L. Nanotechnology for the treatment of melanoma skin cancer. Prog Biomater 2017; 6(1-2): 13-26.
[http://dx.doi.org/10.1007/s40204-017-0064-z] [PMID: 28303522]
[6]
Alfed N, Khelifi F. Bagged textural and color features for melanoma skin cancer detection in dermoscopic and standard images. Expert Syst Appl 2017; 90: 101-10.
[http://dx.doi.org/10.1016/j.eswa.2017.08.010]
[7]
Goyal N, Thatai P, Sapra B. Skin cancer: symptoms, mechanistic pathways and treatment rationale for therapeutic delivery. Ther Deliv 2017; 8(5): 265-87.
[http://dx.doi.org/10.4155/tde-2016-0093] [PMID: 28361609]
[8]
Eisemann N, Jansen L, Castro FA, et al. Survival with nonmelanoma skin cancer in Germany. Br J Dermatol 2016; 174(4): 778-85.
[http://dx.doi.org/10.1111/bjd.14352] [PMID: 26676514]
[9]
Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol 2015; 151(10): 1081-6.
[http://dx.doi.org/10.1001/jamadermatol.2015.1187] [PMID: 25928283]
[10]
National Cancer Institute. SEER Stats Fact Sheets: Melanoma of the skin. http://seer.cancer.gov/statfacts/html/melan.html2016.
[11]
Apalla Z, Nashan D, Weller RB, Castellsagué X. Skin cancer: Epidemiology, disease burden, pathophysiology, diagnosis, and therapeutic approaches. Dermatol Ther (Heidelb) 2017; 7(1)(Suppl. 1): 5-19.
[http://dx.doi.org/10.1007/s13555-016-0165-y] [PMID: 28150105]
[12]
Kumar R, Deep G, Agarwal R. An overview of ultraviolet B radiation-induced skin cancer chemoprevention by silibinin. Curr Pharmacol Rep 2015; 1(3): 206-15.
[http://dx.doi.org/10.1007/s40495-015-0027-9] [PMID: 26097804]
[13]
Amaral T, Garbe C. Non-melanoma skin cancer: new and future synthetic drug treatments. Expert Opin Pharmacother 2017; 18(7): 689-99.
[http://dx.doi.org/10.1080/14656566.2017.1316372] [PMID: 28414587]
[14]
Garrett GL, Blanc PD, Boscardin J, et al. Incidence of and risk factors for skin cancer in organ transplant recipients in the United States. JAMA Dermatol 2017; 153(3): 296-303.
[http://dx.doi.org/10.1001/jamadermatol.2016.4920] [PMID: 28097368]
[15]
Wu S, Han J, Laden F, Qureshi AA. Long-term ultraviolet flux, other potential risk factors, and skin cancer risk: a cohort study. Cancer Epidemiol Biomark Prev 2014.
[16]
Simões MCF, Sousa JJS, Pais AACC. Skin cancer and new treatment perspectives: a review. Cancer Lett 2015; 357(1): 8-42.
[http://dx.doi.org/10.1016/j.canlet.2014.11.001] [PMID: 25444899]
[17]
Locke J, Karimpour S, Young G, Lockett MA, Perez CA. Radiotherapy for epithelial skin cancer. Int J Radiat Oncol Biol Phys 2001; 51(3): 748-55.
[http://dx.doi.org/10.1016/S0360-3016(01)01656-X] [PMID: 11697321]
[18]
Delaney G, Jacob S, Featherstone C, Barton M. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 2005; 104(6): 1129-37.
[http://dx.doi.org/10.1002/cncr.21324] [PMID: 16080176]
[19]
Küchler S, Radowski MR, Blaschke T, et al. Nanoparticles for skin penetration enhancement--a comparison of a dendritic core- multishell-nanotransporter and solid lipid nanoparticles. Eur J Pharm Biopharm 2009; 71(2): 243-50.
[http://dx.doi.org/10.1016/j.ejpb.2008.08.019] [PMID: 18796329]
[20]
Zarekar NS, Lingayat VJ, Pande VV. Nanogel as a novel platform for smart drug delivery system. J Nanosci Nanotechnol 2017; 4(1): 25-31.
[21]
Vicario-de-la-Torre M, Forcada J. The Potential of Stimuli-Responsive Nanogels in Drug and Active Molecule Delivery for Targeted Therapy. Gels 2017; 3(2): 16.
[http://dx.doi.org/10.3390/gels3020016] [PMID: 30920515]
[22]
Ryu JH, Chacko RT, Jiwpanich S, Bickerton S, Babu RP, Thayumanavan S. Self-cross-linked polymer nanogels: a versatile nanoscopic drug delivery platform. J Am Chem Soc 2010; 132(48): 17227-35.
[http://dx.doi.org/10.1021/ja1069932] [PMID: 21077674]
[23]
Chacko RT, Ventura J, Zhuang J, Thayumanavan S. Polymer nanogels: a versatile nanoscopic drug delivery platform. Adv Drug Deliv Rev 2012; 64(9): 836-51.
[http://dx.doi.org/10.1016/j.addr.2012.02.002] [PMID: 22342438]
[24]
Ong YX, Lee LY, Davoodi P, Wang CH. Production of drug-releasing biodegradable microporous scaffold using a two-step micro-encapsulation/supercritical foaming process. J Supercrit Fluids 2018; 133: 263-9.
[http://dx.doi.org/10.1016/j.supflu.2017.10.018]
[25]
Cerqueira BBS, Lasham A, Shelling AN, Al-Kassas R. Development of biodegradable PLGA nanoparticles surface engineered with hyaluronic acid for targeted delivery of paclitaxel to triple negative breast cancer cells. Mater Sci Eng C 2017; 76: 593-600.
[http://dx.doi.org/10.1016/j.msec.2017.03.121] [PMID: 28482569]
[26]
Kumari S, Kondapi AK. Lactoferrin nanoparticle mediated targeted delivery of 5-fluorouracil for enhanced therapeutic efficacy. Int J Biol Macromol 2017; 95: 232-7.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.10.110] [PMID: 27864056]
[27]
Kevadiya BD, Patel TA, Jhala DD, et al. Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU). Eur J Pharm Biopharm 2012; 81(1): 91-101.
[http://dx.doi.org/10.1016/j.ejpb.2012.01.004] [PMID: 22269936]
[28]
Boisdron-Celle M, Capitain O, Faroux R, et al. Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: Assessment of a multiparametric approach. Semin Oncol 2017; 44(1): 13-23.
[http://dx.doi.org/10.1053/j.seminoncol.2017.02.008] [PMID: 28395758]
[29]
Prasanthi D, Lakshmi PK. Terpenes: Effect of lipophilicity in enhancing transdermal delivery of alfuzosin hydrochloride. J Adv Pharm Technol Res 2012; 3(4): 216-23.
[http://dx.doi.org/10.4103/2231-4040.104712] [PMID: 23378942]
[30]
Sahu P, Kashaw SK, Jain S, Sau S, Iyer AK. Assessment of penetration potential of pH responsive double walled biodegradable nanogels coated with eucalyptus oil for the controlled delivery of 5-fluorouracil: In vitro and ex vivo studies. J Control Release 2017; 253: 122-36.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.023] [PMID: 28322977]
[31]
Sapra B, Jain S, Tiwary AK. Percutaneous permeation enhancement by terpenes: mechanistic view. AAPSJ 2008; 10(1): 120-32.
[http://dx.doi.org/10.1208/s12248-008-9012-0] [PMID: 18446512]
[32]
Asghari-Varzaneh E, Shahedi M, Shekarchizadeh H. Iron microencapsulation in gum tragacanth using solvent evaporation method. Int J Biol Macromol 2017; 103: 640-7.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.05.047] [PMID: 28528002]
[33]
Shah P, Bhalodia D, Shelat P. Nanoemulsion: a pharmaceutical review. Sys Rev Pharm 2010; 1(1): 24.
[http://dx.doi.org/10.4103/0975-8453.59509]
[34]
Koul V, Mohamed R, Kuckling D, Adler HJ, Choudhary V. Interpenetrating polymer network (IPN) nanogels based on gelatin and poly(acrylic acid) by inverse miniemulsion technique: synthesis and characterization. Colloids Surf B Biointerfaces 2011; 83(2): 204-13.
[http://dx.doi.org/10.1016/j.colsurfb.2010.11.007] [PMID: 21185698]
[35]
Panonnummal R, Jayakumar R, Sabitha M. Comparative anti-psoriatic efficacy studies of clobetasol loaded chitin nanogel and marketed cream. Eur J Pharm Sci 2017; 96: 193-206.
[http://dx.doi.org/10.1016/j.ejps.2016.09.007] [PMID: 27615594]
[36]
Arun Kumar R, Sivashanmugam A, Deepthi S, et al. Injectable chitin-poly (ε-caprolactone)/nanohydroxyapatite composite microgels prepared by simple regeneration technique for bone tissue engineering. ACS Appl Mater Interfaces 2015; 7(18): 9399-409.
[http://dx.doi.org/10.1021/acsami.5b02685] [PMID: 25893690]
[37]
Ali MS, Alam MS, Alam N, Anwer T, Safhi MM. Accelerated stability testing of a clobetasol propionate-loaded nanoemulsion as per ICH guidelines. Sci Pharm 2013; 81(4): 1089-100.
[http://dx.doi.org/10.3797/scipharm.1210-02] [PMID: 24482775]
[38]
Sahu P, Kashaw SK, Kushwah V, et al. pH responsive biodegradable nanogels for sustained release of bleomycin. Bioorganic Med Chem 2017; 25(17): 4595-613.
[39]
Mangalathillam S, Rejinold NS, Nair A, et al. Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route. Nanoscale 2012; 4(1): 239-50.
[http://dx.doi.org/10.1039/C1NR11271F] [PMID: 22080352]
[40]
Kong M, Park HJ. Stability investigation of hyaluronic acid based nanoemulsion and its potential as transdermal carrier. Carbohydr Polym 2011; 83(3): 1303-10.
[http://dx.doi.org/10.1016/j.carbpol.2010.09.041]
[41]
Anitha A, Chennazhi KP, Nair SV, Jayakumar R. 5-flourouracil loaded N,O-carboxymethyl chitosan nanoparticles as an anticancer nanomedicine for breast cancer. J Biomed Nanotechnol 2012; 8(1): 29-42.
[http://dx.doi.org/10.1166/jbn.2012.1365] [PMID: 22515092]
[42]
Elias ST, Borges GA, Rêgo DF, et al. Combined paclitaxel, cisplatin and fluorouracil therapy enhances ionizing radiation effects, inhibits migration and induces G0/G1 cell cycle arrest and apoptosis in oral carcinoma cell lines. Oncol Lett 2015; 10(3): 1721-7.
[http://dx.doi.org/10.3892/ol.2015.3458] [PMID: 26622739]
[43]
O’Connor NA, Abugharbieh A, Yasmeen F, et al. The crosslinking of polysaccharides with polyamines and dextran-polyallylamine antibacterial hydrogels. Int J Biol Macromol 2015; 72: 88-93.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.08.003] [PMID: 25128095]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy