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Pharmaceutical Nanotechnology

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ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

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Research Article

Niosome-encapsulated Doxycycline Hyclate for Potentiation of Acne Therapy: Formulation and Characterization

Author(s): Fatemeh Kashani-Asadi-Jafari and Afra Hadjizadeh*

Volume 10, Issue 1, 2022

Published on: 18 March, 2022

Page: [56 - 68] Pages: 13

DOI: 10.2174/2211738510666220224103406

Price: $65

Abstract

Background: Acne is the pilosebaceous units' disorder. The most important cause of acne is the colonization of bacteria in the follicles. Among antibiotics, doxycycline hyclate kills a wide range of bacteria.

Objectives: The study aims to prevent oral administration's side effects, overcome the barriers of conventional topical treatment, and improve the therapeutic effectiveness; this drug was loaded into niosomal nanocarriers for topical application.

Methods: Doxycycline hyclate was loaded into four niosomal formulations prepared by the thinfilm hydration method with different percentages of constituents. Drug-containing niosomal systems were evaluated for morphological properties via scanning electron microscopy, particle size, drug entrapment efficiency, zeta potential, in vitro drug release, physical stability after 60 days, in vitro drug permeation through rat skin, in vitro drug deposition in rat skin, toxicity on human dermal fibroblasts (HDF) by MTT method after 72 hours, and antibacterial properties against the main acne-causing bacteria via antibiogram test.

Results: The best formulation had the appropriate particle size of 362.88 ± 13.05 nm to target follicles, entrapment efficiency of 56.3 ± 2.1%, the zeta potential of - 24.46±1.39 mV, in vitro drug release of 54.93 ± 1.99% after 32 hours, and the lowest permeation of the drug through the rat skin among all other formulations. Improved cell viability, increased antibacterial activity, and an approximately three-fold increase in drug deposition were the optimal niosomal formulation features relative to the free drug.

Conclusion: This study demonstrated the ability of nano-niosomes containing doxycycline hyclate to treat skin acne compared with the free drug.

Keywords: Niosome, doxycycline hyclate, pilosebaceous units, acne, antibacterial, thin-film hydration method.

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[1]
Mancuso A, Cristiano MC, Fresta M, Paolino D. The challenge of nanovesicles for selective topical delivery for acne treatment: Enhancing absorption whilst avoiding toxicity. Int J Nanomed 2020; 15: 9197-210.
[http://dx.doi.org/10.2147/IJN.S237508] [PMID: 33239876]
[2]
Dessinioti C, Katsambas AD. The role of Propionibacterium acnes in acne pathogenesis: Facts and controversies. Clin Dermatol 2010; 28(1): 2-7.
[http://dx.doi.org/10.1016/j.clindermatol.2009.03.012] [PMID: 20082942]
[3]
Ruela ALM, Perissinato AG, Lino ME de S, Mudrik PS, Pereira GR. Evaluation of skin absorption of drugs from topical and transdermal formulations. Braz J Pharm Sci 2016; 52(3): 527-44.
[http://dx.doi.org/10.1590/s1984-82502016000300018]
[4]
Patel R, Prabhu P. Nanocarriers as versatile delivery systems for effective management of acne. Int J Pharm 2020; 579119140
[http://dx.doi.org/10.1016/j.ijpharm.2020.119140] [PMID: 32061843]
[5]
Gupta S, Bansal R, Gupta S, Jindal N, Jindal A. Nanocarriers and nanoparticles for skin care and dermatological treatments. Indian Dermatol Online J 2013; 4(4): 267-72.
[http://dx.doi.org/10.4103/2229-5178.120635] [PMID: 24350003]
[6]
Güngör S, Kahraman E. Nanocarriers mediated cutaneous drug delivery. Eur J Pharm Sci 2021; 158105638
[http://dx.doi.org/10.1016/j.ejps.2020.105638] [PMID: 33176190]
[7]
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: Recent developments and future prospects. J Nanobiotechnol 2018; 16(1): 71.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[8]
Castro GA, Ferreira LAM. Novel vesicular and particulate drug delivery systems for topical treatment of acne. Expert Opin Drug Deliv 2008; 5(6): 665-79.
[http://dx.doi.org/10.1517/17425247.5.6.665] [PMID: 18532922]
[9]
Moghassemi S, Hadjizadeh A, Hakamivala A, Omidfar K. Growth factor-loaded nano-niosomal gel formulation and characterization. AAPS PharmSciTech 2017; 18(1): 34-41.
[http://dx.doi.org/10.1208/s12249-016-0579-y] [PMID: 27502406]
[10]
Amoabediny G, Haghiralsadat F, Naderinezhad S, et al. Overview of preparation methods of polymeric and lipid-based (niosome, solid lipid, liposome) nanoparticles: A comprehensive review. Int J Polym Mater 2018; 67(6): 383-400.
[http://dx.doi.org/10.1080/00914037.2017.1332623]
[11]
Chen S, Hanning S, Falconer J, Locke M, Wen J. Recent advances in non-ionic surfactant vesicles (niosomes): Fabrication, characterization, pharmaceutical and cosmetic applications. Eur J Pharm Biopharm 2019; 144: 18-39.
[http://dx.doi.org/10.1016/j.ejpb.2019.08.015] [PMID: 31446046]
[12]
Mahale NB, Thakkar PD, Mali RG, Walunj DR, Chaudhari SR. Niosomes: Novel sustained release nonionic stable vesicular systems - An overview. Adv Colloid Interface Sci 2012; 183-184: 46-54.
[http://dx.doi.org/10.1016/j.cis.2012.08.002] [PMID: 22947187]
[13]
Garg T. Current nanotechnological approaches for an effective delivery of bio-active drug molecules in the treatment of acne. Artif Cells Nanomed Biotechnol 2016; 44(1): 98-105.
[http://dx.doi.org/10.3109/21691401.2014.916715] [PMID: 24844191]
[14]
Kakadia PG, Conway BR. Lipid nanoparticles for dermal drug delivery. Curr Pharm Des 2015; 21(20): 2823-9.
[http://dx.doi.org/10.2174/1381612821666150428143730] [PMID: 25925115]
[15]
Chopra I, Roberts M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 2001; 65(2): 232-60.
[http://dx.doi.org/10.1128/MMBR.65.2.232-260.2001] [PMID: 11381101]
[16]
Goodarzi N, Barazesh Morgani A, Abrahamsson B, et al. Biowaiver monographs for immediate release solid oral dosage forms: Ribavirin. J Pharm Sci 2016; 105(4): 1362-9.
[http://dx.doi.org/10.1016/j.xphs.2016.01.017] [PMID: 26952879]
[17]
Peyriere H, Makinson A, Marchandin H, Reynes J. Doxycycline in the management of sexually transmitted infections. J Antimicrob Chemother 2018; 73(3): 553-63.
[PMID: 29182717]
[18]
Rosso JQD. Oral doxycycline in the management of acne vulgaris: Current perspectives on clinical use and recent findings with a new double-scored small tablet formulation. J Clin Aesthet Dermatol 2015; 8(5): 19-26.
[PMID: 26029331]
[19]
Akbarzadeh I, Yaraki MT, Bourbour M, et al. Optimized doxycycline-loaded niosomal formulation for treatment of infection-associated prostate cancer: An in-vitro investigation. J Drug Deliv Sci Technol 2020; 57101715
[http://dx.doi.org/10.1016/j.jddst.2020.101715]
[20]
Gugleva V, Titeva S, Rangelov S, Momekova D. Design and in vitro evaluation of doxycycline hyclate niosomes as a potential ocular delivery system. Int J Pharm 2019; 567118431
[http://dx.doi.org/10.1016/j.ijpharm.2019.06.022] [PMID: 31207279]
[21]
Dwivedi A, Mazumder A, du Plessis L, du Preez JL, Haynes RK, du Plessis J. In vitro anti-cancer effects of artemisone nano-vesicular formulations on melanoma cells. Nanomed 2015; 11(8): 2041-50.
[http://dx.doi.org/10.1016/j.nano.2015.07.010] [PMID: 26282380]
[22]
Ruckmani K, Jayakar B, Ghosal SK. Nonionic surfactant vesicles (niosomes) of cytarabine hydrochloride for effective treatment of leukemias: Encapsulation, storage, and in vitro release. Drug Dev Ind Pharm 2000; 26(2): 217-22.
[http://dx.doi.org/10.1081/DDC-100100348] [PMID: 10697760]
[23]
Dora CP, Singh SK, Kumar S, Datusalia AK, Deep A. Development and characterization of nanoparticles of glibenclamide by solvent displacement method. Acta Pol Pharm 2010; 67(3): 283-90.
[PMID: 20524431]
[24]
Shah A, Boldhane S, Pawar A, Bothiraja C. Advanced development of a non-ionic surfactant and cholesterol material based niosomal gel formulation for the topical delivery of anti-acne drugs. Mater Adv 2020; 1(6): 1763-74.
[http://dx.doi.org/10.1039/D0MA00298D]
[25]
Plessis J, Egbaria K, Weiner N. Influence of formulation factors on the deposition of liposomal components into the different strata of the skin. J Soc Cosmet Chem 1992; 43: 93-100.
[26]
Ganguly P, Breen A, Pillai SC. Toxicity of nanomaterials: Exposure, pathways, assessment, and recent advances. ACS Biomater Sci Eng 2018; 4(7): 2237-75.
[http://dx.doi.org/10.1021/acsbiomaterials.8b00068] [PMID: 33435097]
[27]
Hashim IIA, El-Magd NFA, El-Sheakh AR, Hamed MF, El-Gawad AEHA. Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: Ex vivo-in vivo evaluation study. Int J Nanomed 2018; 13: 1059-79.
[http://dx.doi.org/10.2147/IJN.S156412] [PMID: 29503541]
[28]
Kumar B, Pathak R, Mary PB, Jha D, Sardana K, Gautam HK. New insights into acne pathogenesis: Exploring the role of acne-associated microbial populations. Zhonghua Pifuke Yixue Zazhi 2016; 34(2): 67-73.
[http://dx.doi.org/10.1016/j.dsi.2015.12.004]
[29]
Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: An illustrated review. J Control Release 2014; 185: 22-36.
[http://dx.doi.org/10.1016/j.jconrel.2014.04.015] [PMID: 24747765]
[30]
Khan R, Irchhaiya R. Niosomes: A potential tool for novel drug delivery. J Pharm Investig 2016; 46(3): 195-204.
[http://dx.doi.org/10.1007/s40005-016-0249-9]
[31]
Agarwal S, Bakshi V, Vitta P, Raghuram AP, Pandey S, Udupa N. Effect of cholesterol content and surfactant HLB on vesicle properties of niosomes. Indian J Pharm Sci 2004; 66: 121-3.
[32]
Kumar GP, Rajeshwarrao P. Nonionic surfactant vesicular systems for effective drug delivery — An overview. Acta Pharm Sin B 2011; 1(4): 208-19.
[http://dx.doi.org/10.1016/j.apsb.2011.09.002]
[33]
Verma DD, Verma S, Blume G, Fahr A. Particle size of liposomes influences dermal delivery of substances into skin. Int J Pharm 2003; 258(1-2): 141-51.
[http://dx.doi.org/10.1016/S0378-5173(03)00183-2] [PMID: 12753761]
[34]
Nasseri B. Effect of cholesterol and temperature on the elastic properties of niosomal membranes. Int J Pharm 2005; 300(1-2): 95-101.
[http://dx.doi.org/10.1016/j.ijpharm.2005.05.009] [PMID: 16006080]
[35]
Essa E. Effect of formulation and processing variables on the particle size of sorbitan monopalmitate niosomes. Asian J Pharm 2010; 4(4): 227-33.
[http://dx.doi.org/10.4103/0973-8398.76752]
[36]
Abdelkader H, Farghaly U, Moharram H. Effects of surfactant type and cholesterol level on niosomes physical properties and in vivo ocular performance using timolol maleate as a model drug. J Pharm Investig 2014; 44(5): 329-37.
[http://dx.doi.org/10.1007/s40005-014-0121-8]
[37]
Lee SC, Lee KE, Kim JJ, Lim SH. The effect of cholesterol in the liposome bilayer on the stabilization of incorporated retinol. J Liposome Res 2005; 15(3-4): 157-66.
[http://dx.doi.org/10.1080/08982100500364131] [PMID: 16393907]
[38]
Reis CP, Gomes A, Rijo P, et al. Development and evaluation of a novel topical treatment for acne with azelaic acid-loaded nanoparticles. Microsc Microanal 2013; 19(5): 1141-50.
[http://dx.doi.org/10.1017/S1431927613000536] [PMID: 23673203]
[39]
Hao Y, Zhao F, Li N, Yang Y, Li K. Studies on a high encapsulation of colchicine by a niosome system. Int J Pharm 2002; 244(1-2): 73-80.
[http://dx.doi.org/10.1016/S0378-5173(02)00301-0] [PMID: 12204566]
[40]
Moghassemi S, Hadjizadeh A, Omidfar K. Formulation and characterization of bovine serum albumin-loaded niosome. AAPS PharmSciTech 2017; 18(1): 27-33.
[http://dx.doi.org/10.1208/s12249-016-0487-1] [PMID: 26817764]
[41]
Yoshioka T, Sternberg B, Florence AT. Preparation and properties of vesicles (niosomes) of sorbitan monoesters (span 20, 40, 60 and 80) and a sorbitan triester (span 85). Int J Pharm 1994; 105(1): 1-6.
[http://dx.doi.org/10.1016/0378-5173(94)90228-3]
[42]
Latter G, Grice JE, Mohammed Y, Roberts MS, Benson HAE. Targeted topical delivery of retinoids in the management of Acne vulgaris: Current formulations and novel delivery systems. Pharmaceutics 2019; 11(10): 490.
[http://dx.doi.org/10.3390/pharmaceutics11100490] [PMID: 31554188]
[43]
Morykwas MJ, Thornton JW, Bartlett RH. Zeta potential of synthetic and biological skin substitutes: Effects on initial adherence. Plast Reconstr Surg 1987; 79(5): 732-9.
[http://dx.doi.org/10.1097/00006534-198705000-00009] [PMID: 3554286]
[44]
Zhang Y, Jing Q, Hu H, et al. Sodium dodecyl sulfate improved stability and transdermal delivery of salidroside-encapsulated niosomes via effects on zeta potential. Int J Pharm 2020; 580119183
[http://dx.doi.org/10.1016/j.ijpharm.2020.119183] [PMID: 32112930]
[45]
Freitas C, Müller RH. Effect of light and temperature on zeta potential and physical stability in Solid Lipid Nanoparticle (SLN®) dispersions. Int J Pharm 1998; 168(2): 221-9.
[http://dx.doi.org/10.1016/S0378-5173(98)00092-1]
[46]
Soussan E, Cassel S, Blanzat M, Rico-Lattes I. Drug delivery by soft matter: Matrix and vesicular carriers. Angew Chem Int Ed Engl 2009; 48(2): 274-88.
[http://dx.doi.org/10.1002/anie.200802453] [PMID: 19072808]
[47]
Ghafelehbashi R, Akbarzadeh I, Yaraki MT, Lajevardi A, Fatemizadeh M, Saremi LH. Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes. Int J Pharm 2019; 569118580
[http://dx.doi.org/10.1016/j.ijpharm.2019.118580] [PMID: 31374239]
[48]
Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010; 67(3): 217-23.
[PMID: 20524422]
[49]
Fu Y, Kao WJ. Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert Opin Drug Deliv 2010; 7(4): 429-44.
[http://dx.doi.org/10.1517/17425241003602259] [PMID: 20331353]
[50]
Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 1987; 5(1): 37-42.
[http://dx.doi.org/10.1016/0168-3659(87)90035-6]
[51]
Kassem AA, El-Alim SHA, Asfour MH. Enhancement of 8-methoxypsoralen topical delivery via nanosized niosomal vesicles: Formulation development, in vitro and in vivo evaluation of skin deposition. Int J Pharm 2017; 517(1-2): 256-68.
[http://dx.doi.org/10.1016/j.ijpharm.2016.12.018] [PMID: 27956194]
[52]
Hasan AA, Madkor H, Wageh S. Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system. Drug Deliv 2013; 20(3-4): 120-6.
[http://dx.doi.org/10.3109/10717544.2013.779332] [PMID: 23651102]
[53]
Pardakhty A, Moazeni E, Varshosaz J, Hajhashemi V, Najafabadi AR. Pharmacokinetic study of niosome-loaded insulin in diabetic rats. Daru 2011; 19(6): 404-11.
[PMID: 23008685]
[54]
Ibrahim MM, Shehata TM. The enhancement of transdermal permeability of water soluble drug by niosome-emulgel combination. J Drug Deliv Sci Technol 2012; 22(4): 353-9.
[http://dx.doi.org/10.1016/S1773-2247(12)50059-6]
[55]
Godin B, Touitou E. Transdermal skin delivery: Predictions for humans from in vivo, ex vivo and animal models. Adv Drug Deliv Rev 2007; 59(11): 1152-61.
[http://dx.doi.org/10.1016/j.addr.2007.07.004] [PMID: 17889400]
[56]
Aziz DE, Abdelbary AA, Elassasy AI. Implementing central composite design for developing transdermal diacerein-loaded niosomes: Ex vivo permeation and in vivo deposition. Curr Drug Deliv 2018; 15(9): 1330-42.
[http://dx.doi.org/10.2174/1567201815666180619105419] [PMID: 29921206]
[57]
Fang JY, Hong CT, Chiu WT, Wang YY. Effect of liposomes and niosomes on skin permeation of enoxacin. Int J Pharm 2001; 219(1-2): 61-72.
[http://dx.doi.org/10.1016/S0378-5173(01)00627-5] [PMID: 11337166]
[58]
Abdelbary AA, AbouGhaly MHH. Design and optimization of topical methotrexate loaded niosomes for enhanced management of psoriasis: Application of Box-Behnken design, in-vitro evaluation and in-vivo skin deposition study. Int J Pharm 2015; 485(1-2): 235-43.
[http://dx.doi.org/10.1016/j.ijpharm.2015.03.020] [PMID: 25773359]
[59]
Kaur D, Kumar S. Niosomes: Present scenario and future aspects. J Drug Deliv Ther 2018; 8(5): 35-43.
[http://dx.doi.org/10.22270/jddt.v8i5.1886]
[60]
Mehta SK, Jindal N, Kaur G. Quantitative investigation, stability and in vitro release studies of anti-TB drugs in Triton niosomes. Colloids Surf B 2011; 87(1): 173-9.
[http://dx.doi.org/10.1016/j.colsurfb.2011.05.018] [PMID: 21640561]

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