Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Preparation and Evaluation of Liposomes Containing Ethanol and Propylene Glycol as Carriers for Nicotine

Author(s): Hui Wang, Qing Shao, Yan Zhang, Jing Ding, Miaomiao Yang, Liu Yang, Wenjie Wang, Pengfei Cui, Zunxiao Dai and Li Ma*

Volume 21, Issue 2, 2024

Published on: 11 May, 2023

Page: [249 - 260] Pages: 12

DOI: 10.2174/1567201820666230428122845

Price: $65

Abstract

Background: Nicotine is a fat-soluble substance that is easily absorbed through the skin and mucosal tissues of the human body. However, its properties, such as light exposure, heat decomposition, and volatilization, restrict its development and application in external preparations.

Objective: This study focused on the preparation of stable nicotine-encapsulated ethosomes.

Methods: During their preparation, two water-phase miscible osmotic promoters, ethanol and propylene glycol (PG), were added to obtain a stable transdermal delivery system. Skin nicotine delivery was enhanced through the synergistic action of osmotic promoters and phosphatidylcholine in binary ethosomes. Various characteristics of the binary ethosomes were measured, including the vesicle size, particle size distribution, and zeta potential. In order to optimize the ratio of ethanol and PG, the skin permeability test was performed on mice in vitro in a Franz diffusion cell to compare cumulative skin permeabilities. The penetration depth and fluorescence intensity of rhodamine-B-entrapped vesicles in isolated mouse skin samples were observed using laser confocal scanning microscopy.

Results: When ethanol:PG was used in a ratio of 5:5 (w/w), binary ethosomes were found to be the most stable, had the highest encapsulation rate (86.13 ± 1.40), smallest particle size (106.0 ± 11.0) nm, maximum transdermal depth (180 μm), and maximum fluorescence intensity (160 AU). Nicotineencapsulated ethosomes (ethanol: PG = 5:5, w/w) were an efficient and stable transdermal delivery system.

Conclusion: The nicotine-encapsulated ethosomes containing ethanol and PG are considered to be safe and reliable as a transdermal administration agent, which does not irritate the skin.

Keywords: Nicotine, binary ethosomes, propylene glycol, transdermal delivery, fluorescence intensity, Franz diffusion cell.

Graphical Abstract
[1]
Waghule, T.; Singhvi, G.; Dubey, S.K.; Pandey, M.M.; Gupta, G.; Singh, M.; Dua, K. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomed. Pharmacother., 2019, 109, 1249-1258.
[http://dx.doi.org/10.1016/j.biopha.2018.10.078] [PMID: 30551375]
[2]
Yang, D.; Chen, M.; Sun, Y.; Jin, Y.; Lu, C.; Pan, X.; Quan, G.; Wu, C. Microneedle-mediated transdermal drug delivery for treating diverse skin diseases. Acta Biomater., 2021, 121, 119-133.
[http://dx.doi.org/10.1016/j.actbio.2020.12.004] [PMID: 33285323]
[3]
Yoshida, M.; Uchida, S.; Kashiwagura, Y.; Tanaka, S.; Matsui, R.; Namiki, N. Evaluation of in vitro and in vivo transdermal Absorption of solifenacin succinate. Chem. Pharm. Bull., 2019, 67(11), 1225-1231.
[http://dx.doi.org/10.1248/cpb.c19-00552] [PMID: 31685750]
[4]
Kováčik, A.; Kopečná, M.; Vávrová, K. Permeation enhancers in transdermal drug delivery: Benefits and limitations. Expert Opin. Drug Deliv., 2020, 17(2), 145-155.
[http://dx.doi.org/10.1080/17425247.2020.1713087] [PMID: 31910342]
[5]
Ruan, S.; Zhang, Y.; Feng, N. Microneedle-mediated transdermal nanodelivery systems: A review. Biomater. Sci., 2021, 9(24), 8065-8089.
[http://dx.doi.org/10.1039/D1BM01249E] [PMID: 34752590]
[6]
Paiva-Santos, A.C.; Silva, A.L.; Guerra, C.; Peixoto, D.; Pereira-Silva, M.; Zeinali, M.; Mascarenhas-Melo, F.; Castro, R.; Veiga, F. Ethosomes as nanocarriers for the development of skin delivery formulations. Pharm. Res., 2021, 38(6), 947-970.
[http://dx.doi.org/10.1007/s11095-021-03053-5] [PMID: 34036520]
[7]
Natsheh, H.; Vettorato, E.; Touitou, E. Ethosomes for dermal administration of natural active molecules. Curr. Pharm. Des., 2019, 25(21), 2338-2348.
[http://dx.doi.org/10.2174/1381612825666190716095826] [PMID: 31333087]
[8]
Garg, V.; Singh, H.; Bimbrawh, S.; Singh, S.K.; Gulati, M.; Vaidya, Y.; Kaur, P. Ethosomes and transfersomes: Principles, perspectives and practices. Curr. Drug Deliv., 2017, 14(5), 613-633.
[PMID: 27199229]
[9]
Sguizzato, M.; Ferrara, F.; Hallan, S.S.; Baldisserotto, A.; Drechsler, M.; Malatesta, M.; Costanzo, M.; Cortesi, R.; Puglia, C.; Valacchi, G.; Esposito, E. Ethosomes and transethosomes for mangiferin transdermal delivery. Antioxidants, 2021, 10(5), 768.
[http://dx.doi.org/10.3390/antiox10050768] [PMID: 34066018]
[10]
Ma, H.; Guo, D.; Fan, Y.; Wang, J.; Cheng, J.; Zhang, X. Paeonol-loaded ethosomes as transdermal delivery carriers: Design, preparation and evaluation. Molecules, 2018, 23(7), 1756.
[http://dx.doi.org/10.3390/molecules23071756] [PMID: 30018278]
[11]
Adki, K.M.; Kulkarni, Y.A. Chemistry, pharmacokinetics, pharmacology and recent novel drug delivery systems of paeonol. Life Sci., 2020, 250, 117544.
[http://dx.doi.org/10.1016/j.lfs.2020.117544] [PMID: 32179072]
[12]
Sailer, S.; Sebastiani, G.; Andreu-Férnández, V.; García-Algar, O. Impact of nicotine replacement and electronic nicotine delivery systems on fetal brain development. Int. J. Environ. Res. Public Health, 2019, 16(24), 5113.
[http://dx.doi.org/10.3390/ijerph16245113] [PMID: 31847348]
[13]
Shi, R.; Feldman, R.; Liu, J.; Clark, P.I. The dilemma of correcting nicotine misperceptions: Nicotine replacement therapy versus electronic cigarettes. Health Commun., 2021, 36(14), 1856-1866.
[http://dx.doi.org/10.1080/10410236.2020.1800288] [PMID: 32762261]
[14]
Valentine, G.; Sofuoglu, M. Cognitive effects of nicotine: Recent progress. Curr. Neuropharmacol., 2018, 16(4), 403-414.
[http://dx.doi.org/10.2174/1570159X15666171103152136] [PMID: 29110618]
[15]
Cheng, Y.C.; Li, T.S.; Su, H.L.; Lee, P.C.; Wang, H.M.D. Transdermal delivery systems of natural products applied to skin therapy and care. Molecules, 2020, 25(21), 5051.
[http://dx.doi.org/10.3390/molecules25215051] [PMID: 33143260]
[16]
Wen, X.; Xin, Y.; Hamblin, M.R.; Jiang, X. Applications of cold atmospheric plasma for transdermal drug delivery: A review. Drug Deliv. Transl. Res., 2021, 11(3), 741-747.
[http://dx.doi.org/10.1007/s13346-020-00808-2] [PMID: 32562255]
[17]
Rehder Silinski, M.A.; Uenoyama, T.; Coleman, D.P.; Blake, J.C.; Thomas, B.F.; Marusich, J.A.; Jackson, K.J.; Meredith, S.E.; Gahl, R.F. Analysis of nicotine and non-nicotine tobacco constituents in aqueous smoke/aerosol extracts by UHPLC and ultraperformance convergence chromatography–tandem mass spectrometry. Chem. Res. Toxicol., 2020, 33(12), 2988-3000.
[http://dx.doi.org/10.1021/acs.chemrestox.0c00312] [PMID: 33226218]
[18]
Moolakkadath, T.; Aqil, M.; Ahad, A.; Imam, S.S.; Praveen, A.; Sultana, Y.; Mujeeb, M.; Iqbal, Z. Fisetin loaded binary ethosomes for management of skin cancer by dermal application on UV exposed mice. Int. J. Pharm., 2019, 560, 78-91.
[http://dx.doi.org/10.1016/j.ijpharm.2019.01.067] [PMID: 30742987]
[19]
Sorensen, E.N.; Weisman, G.; Vidaver, G.A. A Sephadex column for measuring uptake and loss of low molecular weight solutes from small vesicles. Anal. Biochem., 1977, 82, 376-384.
[http://dx.doi.org/10.1016/0003-2697(77)90175-0] [PMID: 562078]
[20]
Fry, D.W.; White, J.C.; Goldman, I.D. Rapid separation of low molecular weight solutes from liposomes without dilution. Anal. Biochem., 1978, 90(2), 809-815.
[http://dx.doi.org/10.1016/0003-2697(78)90172-0] [PMID: 727510]
[21]
Committee of National Pharmacopoeia. Pharmacopoeia of P.R. China; Chemical Industry Press: Beijing, 2020.
[22]
F, A.G.; Sayed, O.M.; Abo El-Ela, F.I.; Kharshoum, R.M.; Salem, H.F. Treatment of basal cell carcinoma via binary ethosomes of vismodegib: in vitro and in vivo studies. AAPS PharmSciTech, 2020, 21(2), 51.
[http://dx.doi.org/10.1208/s12249-019-1574-x] [PMID: 31900659]
[23]
Paliwal, S.; Tilak, A.; Sharma, J.; Dave, V.; Sharma, S.; Yadav, R.; Patel, S.; Verma, K.; Tak, K. Flurbiprofen loaded ethosomes - transdermal delivery of anti-inflammatory effect in rat model. Lipids Health Dis., 2019, 18(1), 133.
[http://dx.doi.org/10.1186/s12944-019-1064-x] [PMID: 31170970]
[24]
Akhtar, N.; Verma, A.; Pathak, K. Feasibility of binary composition in development of nanoethosomal glycolic vesicles of triamcinolone acetonide using Box-behnken design: in vitro and ex vivo characterization. Artif. Cells Nanomed. Biotechnol., 2017, 45(6), 1123-1131.
[http://dx.doi.org/10.1080/21691401.2016.1202261] [PMID: 27367965]
[25]
Caddeo, C.; Sales, O.D.; Valenti, D.; Saurí, A.R.; Fadda, A.M.; Manconi, M. Inhibition of skin inflammation in mice by diclofenac in vesicular carriers: Liposomes, ethosomes and PEVs. Int. J. Pharm., 2013, 443(1-2), 128-136.
[http://dx.doi.org/10.1016/j.ijpharm.2012.12.041] [PMID: 23299087]
[26]
Kawar, D.; Abdelkader, H. Hyaluronic acid gel-core liposomes (hyaluosomes) enhance skin permeation of ketoprofen. Pharm. Dev. Technol., 2019, 24(8), 947-953.
[http://dx.doi.org/10.1080/10837450.2019.1572761] [PMID: 30676142]
[27]
Khan, H.M.S.; Javed, N.; Ijaz, S.; Akhtar, N. Nanostructured ethosomal gel loaded with arctostaphylosuva-ursi extract; in-vitro/in-vivo evaluation as a cosmeceutical product for skin rejuvenation. Curr. Drug Deliv., 2022, 19(6), 706-720.
[http://dx.doi.org/10.2174/1567201818666210729111026] [PMID: 34325633]
[28]
Zhang, J.P.; Wei, Y.H.; Zhou, Y.; Li, Y.Q.; Wu, X.A. Ethosomes, binary ethosomes and transfersomes of terbinafine hydrochloride: A comparative study. Arch. Pharm. Res., 2012, 35(1), 109-117.
[http://dx.doi.org/10.1007/s12272-012-0112-0] [PMID: 22297749]
[29]
Jain, S.; Tiwary, A.K.; Sapra, B.; Jain, N.K. Formulation and evaluation of ethosomes for transdermal delivery of lamivudine. AAPS PharmSciTech, 2007, 8(4), 249.
[http://dx.doi.org/10.1208/pt0804111] [PMID: 18181532]
[30]
Shang, M.; Sun, J. Vitamin D/VDR, probiotics, and gastrointestinal diseases. Curr. Med. Chem., 2017, 24(9), 876-887.
[http://dx.doi.org/10.2174/0929867323666161202150008] [PMID: 27915988]
[31]
Sguizzato, M.; Mariani, P.; Spinozzi, F.; Benedusi, M.; Cervellati, F.; Cortesi, R.; Drechsler, M.; Prieux, R.; Valacchi, G.; Esposito, E. Ethosomes for coenzyme Q10 cutaneous administration: From design to 3d skin tissue evaluation. Antioxidants, 2020, 9(6), 485.
[http://dx.doi.org/10.3390/antiox9060485] [PMID: 32503293]
[32]
Zhou, Y.; Wei, Y.; Liu, H.; Zhang, G.; Wu, X. Preparation and in vitro evaluation of ethosomal total alkaloids of Sophora alopecuroides loaded by a transmembrane pH-gradient method. AAPS PharmSciTech, 2010, 11(3), 1350-1358.
[http://dx.doi.org/10.1208/s12249-010-9509-6] [PMID: 20740333]
[33]
Das, S.K.; Chakraborty, S.; Roy, C.; Rajabalaya, R.; Mohaimin, A.W.; Khanam, J.; Nanda, A.; David, S.R. Ethosomes as novel vesicular carrier: An overview of the principle, preparation and its applications. Curr. Drug Deliv., 2018, 15(6), 795-817.
[http://dx.doi.org/10.2174/1567201815666180116091604] [PMID: 29336262]
[34]
Khan, M.Z.U.; Khan, S.A.; Ubaid, M.; Shah, A.; Kousar, R.; Murtaza, G. Finasteride topical delivery systems for androgenetic alopecia. Curr. Drug Deliv., 2018, 15(8), 1100-1111.
[http://dx.doi.org/10.2174/1567201815666180124112905] [PMID: 29366416]
[35]
Niu, X.Q.; Zhang, D.P.; Bian, Q.; Feng, X.F.; Li, H.; Rao, Y.F.; Shen, Y.M.; Geng, F.N.; Yuan, A.R.; Ying, X.Y.; Gao, J.Q. Mechanism investigation of ethosomes transdermal permeation. Int. J. Pharm. X, 2019, 1, 100027.
[http://dx.doi.org/10.1016/j.ijpx.2019.100027] [PMID: 31517292]

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