Login Register Cart 0
Generic placeholder image

Nanoscience & Nanotechnology-Asia

Editor-in-Chief

ISSN (Print): 2210-6812
ISSN (Online): 2210-6820

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Design and Optimization of Itraconazole Loaded SLN for Intranasal Administration Using Central Composite Design

Author(s): Sarvjeet S. Rana, Shailendra Bhatt*, Manish Kumar, Anuj Malik, Jai B. Sharma, Deepshi Arora and Vipin Saini

Volume 10, Issue 6, 2020

Page: [884 - 891] Pages: 8

DOI: 10.2174/2210681209666191111113112

Price: $65

Abstract

Introduction: Solid Lipid nanoparticles (SLN) are comprising of a solid lipid core with a mean diameter between 50 and 1000 nm. SLN is an advanced carrier system to traditional colloidal carriers such as emulsion, liposomes, and polymeric microparticles.

Objective: The objective of this study was to formulate SLN of Itraconazole (ITZ) for intranasal administration.

Methods: ITZ-loaded SLN were prepared by high pressure homogenization technique using the Central Composite Design (CCD). The concentration of surfactant (X1) and drug to lipid ratio (X2) was considered as independent variables, whereas particle size (Y1) and percentage entrapment efficiency (Y2) were considered as a response. The compatibility of ingredients with the drug was tested using differential scanning calorimetry. SLN were characterized for their particle size, entrapment efficiency, transmission electron microscopy, in vitro drug release, and ex vivo study.

Results: The solid lipid nanoparticles were successfully prepared using high pressure homogenization technique and glyceryl monostearate was used as solid lipid. The lipid ratio significantly increases the particle size as well as entrapment efficiency. The particle size and (%) entrapment efficiency of optimized formulation were found to be 29 nm and 78.9%, respectively. The differential scanning calorimetry confirmed that the drug existed in amorphous form. Nasal histopathology study on sheep mucosa revealed that the developed SLN was non-toxic and safe to use for intranasal administration. The results of ex vivo study showed that the Higuchi pattern of drug release was followed. The in vitro release studies showed the significant difference in drug release from ITZ-loaded SLN compared to plain ITZ-solution.

Conclusion: ITZ-loaded SLN were successfully prepared and validated. The best batch was selected based on the desired particle size, and EE which is an important characteristic for SLN formulations. The developed formulations were nontoxic as determined by histo-pathological studies.

Keywords: SLN, nasal histopathology, ex vivo, optimization, high pressure homogenization, reticulo endothelial system.

Graphical Abstract

[1]
Patel, S.; Chavhan, S.; Soni, H.; Babbar, A.K.; Mathur, R.; Mishra, A.K.; Sawant, K. Brain targeting of risperidone-loaded solid lipid nanoparticles by intranasal route. J. Drug Target., 2011, 19(6), 468-474.
[http://dx.doi.org/10.3109/1061186X.2010.523787] [PMID: 20958095]
[2]
Perfect, J.R.; Durack, D.T. Penetration of imidazoles and triazoles into cerebrospinal fluid of rabbits. J. Antimicrob. Chemother., 1985, 16(1), 81-86.
[http://dx.doi.org/10.1093/jac/16.1.81] [PMID: 2995303]
[3]
Chariyalertsak, S.; Supparatpinyo, K.; Sirisanthana, T.; Nelson, K.E. A controlled trial of itraconazole as primary prophylaxis for systemic fungal infections in patients with advanced human immunodeficiency virus infection in Thailand. Clin. Infect. Dis., 2002, 34(2), 277-284.
[http://dx.doi.org/10.1086/338154] [PMID: 11740718]
[4]
Denning, D.W.; Tucker, R.M.; Hanson, L.H.; Hamilton, J.R.; Stevens, D.A. Itraconazole therapy for cryptococcal meningitis and cryptococcosis. Arch. Intern. Med., 1989, 149(10), 2301-2308.
[http://dx.doi.org/10.1001/archinte.1989.00390100107024] [PMID: 2552949]
[5]
Van Cutsem, J.; Van Gerven, F.; Van de Ven, M.A.; Borgers, M.; Janssen, P.A. Itraconazole, a new triazole that is orally active in aspergillosis. Antimicrob. Agents Chemother., 1984, 26(4), 527-534.
[http://dx.doi.org/10.1128/AAC.26.4.527] [PMID: 6097167]
[6]
Kaplan, J.E.; Benson, C.; Holmes, K.K.; Brooks, J.T.; Pau, A.; Masur, H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm. Rep., 2009, 58(RR-4), 1-207.
[PMID: 19357635]
[7]
Fuller, L.C.; Barton, R.C.; Mohd Mustapa, M.F. Proud foot, L.E.; Punjabi, S.P.; Higgins, E.M. British Association of Dermatologists’ guidelines for themanagement of tinea capitis 2014. Br. J. Dermatol., 2014, 171, 454-463.
[http://dx.doi.org/10.1111/bjd.13196] [PMID: 25234064]
[8]
Ferreira, P.; Noronha, L.; Teixeira, R.; Vieira, Í.; Borba-Santos, L.; Viçosa, A.; de Moraes, M.; Calil-Elias, S.; de Freitas, Z.; da Silva, F.; Rozental, S.; Futuro, D.; Ferreira, V. Investigation of a microemulsion containing clotrimazole and itraconazole for transdermal delivery for the treatment of sporotrichosis. J. Pharm. Sci., 2019, 2019. S0022-3549(19)30644-6.
[http://dx.doi.org/10.1016/j.xphs.2019.10.009] [PMID: 31604084]
[9]
Solanki, N.G.; Lam, K.; Tahsin, M.; Gumaste, S.G.; Shah, A.V.; Serajuddin, A.T.M. Effects of surfactants on itraconazole-HPMCAS solid dispersion prepared by hot-melt extrusion I: Miscibility and drug release. J. Pharm. Sci., 2019, 108(4), 1453-1465.
[http://dx.doi.org/10.1016/j.xphs.2018.10.058] [PMID: 30395834]
[10]
Bian, X.; Liang, S.; John, J.; Hsiao, C.H.; Wei, X.; Liang, D.; Xie, H. Development of PLGA-based itraconazole injectable nanospheres for sustained release. Int. J. Nanomedicine, 2013, 8, 4521-4531.
[PMID: 24311942]
[11]
Lim, W.M.; Rajinikanth, P.S.; Mallikarjun, C.; Kang, Y.B. Formulation and delivery of itraconazole to the brain using a nanolipid carrier system. Int. J. Nanomedicine, 2014, 9, 2117-2126.
[http://dx.doi.org/10.2147/IJN.S57565] [PMID: 24833900]
[12]
Qiu, L.; Hu, B.; Chen, H.; Li, S.; Hu, Y.; Zheng, Y.; Wu, X. Antifungal efficacy of itraconazole-loaded TPGS-b-(PCL-ran-PGA) nanoparticles. Int. J. Nanomedicine, 2015, 10, 1415-1423.
[PMID: 25733833]
[13]
Zhu, Z.; Huang, Z.; Li, Z.; Li, X.; Du, C.; Tian, Y. Multiple brain abscesses caused by infection with Candida glabrata: A case report. Exp. Ther. Med., 2018, 15(3), 2374-2380.
[PMID: 29456643]
[14]
Pace, J.R.; Jog, R.; Burgess, D.J.; Hadden, M.K. Formulation and evaluation of itraconazole liposomes for Hedgehog pathway inhibition. J. Liposome Res., 2019, 1-7.
[http://dx.doi.org/10.1080/08982104.2019.1668011] [PMID: 31576768]
[15]
Ćurić, A.; Möschwitzer, J.P.; Fricker, G. Development and characterization of novel highly-loaded itraconazole poly(butyl cyanoacrylate) polymeric nanoparticles. Eur. J. Pharm. Biopharm., 2017, 114, 175-185.
[http://dx.doi.org/10.1016/j.ejpb.2017.01.014] [PMID: 28159723]
[16]
Bhatt, S.; Sharma, J.; Singh, M.; Saini, V. Solid lipid nanoparticles: A promising technology for delivery of poorly water-soluble drugs. ACTA Pharmaceut. Sci., 2018, 56, 3.
[http://dx.doi.org/10.23893/1307-2080.APS.05616]
[17]
Ezzati Nazhad Dolatabadi, J.; Hamishehkar, H.; Eskandani, M.; Valizadeh, H. Formulation, characterization and cytotoxicity studies of alendronate sodium-loaded solid lipid nanoparticles. Colloids Surf. B Biointerfaces, 2014, 117, 21-28.
[http://dx.doi.org/10.1016/j.colsurfb.2014.01.055] [PMID: 24607519]
[18]
Jain, K.; Kumar, R.S.; Sood, S.; Dhyanandhan, G. Betaxolol hydrochloride loaded chitosan nanoparticles for ocular delivery and their anti-glaucoma efficacy. Curr. Drug Deliv., 2013, 10(5), 493-499.
[http://dx.doi.org/10.2174/1567201811310050001] [PMID: 23410069]
[19]
Sood, S.; Jawahar, N.; Jain, K.; Kuppusamy, G.; Subramania, N.M. Olanzapine loaded cationic solid lipid nanoparticles for improved oral bioavailability. Curr. Nanosci., 2013, 9, 26-34.
[20]
Seju, U.; Kumar, A.; Sawant, K.K. Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: In vitro and in vivo studies. Acta Biomater., 2011, 7(12), 4169-4176.
[http://dx.doi.org/10.1016/j.actbio.2011.07.025] [PMID: 21839863]
[21]
Luo, Y.; Chen, D.; Ren, L.; Zhao, X.; Qin, J. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J. Control. Release, 2006, 114(1), 53-59.
[http://dx.doi.org/10.1016/j.jconrel.2006.05.010] [PMID: 16828192]
[22]
Jain, K.; Sood, S.; Gowthamarajan, K. Optimization of artemether-loaded NLC for intranasal delivery using central composite design. Drug Deliv., 2015, 22(7), 940-954.
[http://dx.doi.org/10.3109/10717544.2014.885999] [PMID: 24512368]
[23]
Shailendra, B.; Shailendra, M.; Manish, J.; Singh, T.Y.; Priti, T. Design and optimization of domperidone fast dissolving tablet using central composite design. Curr. Drug Deliv., 2015, 12(6), 736-744.
[http://dx.doi.org/10.2174/1567201811666141022101415] [PMID: 25335985]

Rights & Permissions Print Cite
Article Metrics
15
© 2024 Bentham Science Publishers | Privacy Policy