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Nanoscience & Nanotechnology-Asia

Editor-in-Chief

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

Research Article

Optimization and Fabrication of Curcumin Loaded Solid Lipid Nanoparticles Using Box-Behnken Design for Nasal Delivery

Author(s): Sherry Sharma, Jai Bharti Sharma, Shailendra Bhatt* and Manish Kumar

Volume 12, Issue 6, 2022

Published on: 24 November, 2022

Article ID: e031122210625 Pages: 12

DOI: 10.2174/2210681213666221103151333

Price: $65

Abstract

Aims: To prepare curcumin loaded solid lipid nanoparticles for nasal administration using Box-Behnken design.

Background: The effectiveness of curcumin in neurological disorders is widely studied by various researchers, but its use is limited due to its poor bioavailability. The brain-targeting efficiency of curcumin can be improved using solid lipid nanoparticles via nasal administration.

Objective: In the present work, Curcumin loaded solid lipid nanoparticles (CUR-SLN) were formulated and optimized for nasal administration.

Methods: Based on solubility studies, cetostearyl alcohol and poloxamer 407 were selected as lipid and surfactant, respectively. Box-Behnken design (BBD) was used to analyze the effects of drug-to-lipid ratio (X1), surfactant concentration (X2) and homogenization time (X3) on particle size (Y1) and % entrapment efficiency (Y2). The CUR-SLN were formulated by the high shear homogenization method. The optimized formulation was evaluated for DSC, TEM, drug release and ex-vivo studies.

Results: Good results were obtained for the particle size and entrapment efficiency analyzed using BBD. The optimized formulation of CUR-SLN obtained using BBD was observed with a particle size of 96.09 nm and % EE of 78.23. In-vitro release of the drug was found to be 82.93± 0.15% after 8 hours. DSC studies revealed that crystalline form of curcumin changed to an amorphous form in SLN. TEM results of optimized CUR-SLN were in correlation with the results obtained using a zeta sizer. No harmful effects were observed on nasal mucosa in the histopathology study.

Conclusion: The SLN can be safely utilized for the intranasal administration of curcumin.

Graphical Abstract

[1]
Aderibigbe, B.A. In situ-based gels for nose to brain delivery for the treatment of neurological diseases. Pharmaceutics, 2018, 10(2), 40.
[http://dx.doi.org/10.3390/pharmaceutics10020040] [PMID: 29601486]
[2]
Meng, Q.; Wang, A.; Hua, H.; Jiang, Y.; Wang, Y.; Mu, H.; Wu, Z.; Sun, K. Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease. Int. J. Nanomedicine, 2018, 13, 705-718.
[http://dx.doi.org/10.2147/IJN.S151474] [PMID: 29440896]
[3]
Potter, P.E. Curcumin: A natural substance with potential efficacy in Alzheimer’s disease. J. Exp. Pharmacol., 2013, 5, 23-31.
[http://dx.doi.org/10.2147/JEP.S26803] [PMID: 27186134]
[4]
Alexander, A.; Saraf, S. Nose to brain drug delivery approach: A key to easily accessing the brain for the treatment of Alzheimer’s disease. Neural Regen. Res., 2018, 13(12), 2102-2104.
[http://dx.doi.org/10.4103/1673-5374.241458] [PMID: 30323136]
[5]
Prasad, S.; Gupta, S.C.; Tyagi, A.K.; Aggarwal, B.B. Curcumin, a component of golden spice: From bedside to bench and back. Biotechnol. Adv., 2014, 32(6), 1053-1064.
[http://dx.doi.org/10.1016/j.biotechadv.2014.04.004] [PMID: 24793420]
[6]
Hewlings, S.J.; Kalman, D.S. Curcumin: A review of its’ effects on human health. Foods, 2017, 6(10), 92.
[http://dx.doi.org/10.3390/foods6100092] [PMID: 29065496]
[7]
Goel, A.; Jhurani, S.; Aggarwal, B.B. Multi targeted therapy by curcumin: How spicy is it? Mol. Nutr. Food Res., 2008, 52(9), 1010-1030.
[http://dx.doi.org/10.1002/mnfr.200700354] [PMID: 18384098]
[8]
Nelson, K.M.; Dahlin, J.L.; Bisson, J.; Graham, J.; Pauli, G.F.; Walters, M.A. The essential medicinal chemistry of curcumin. J. Med. Chem., 2017, 60(5), 1620-1637.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00975] [PMID: 28074653]
[9]
Sharma, J.B.; Bhatt, S.; Sharma, A.; Kumar, M. Recent advances in curcumin nanocarriers for the treatment of different types of cancer with special emphasis on in vitro cytotoxicity and cellular uptake studies. Nanosci. Nanotechnol. Asia, 2020, 10(5), 577-590.
[http://dx.doi.org/10.2174/2210681209666190417144126]
[10]
Reddy, P.H.; Manczak, M.; Yin, X.; Grady, M.C.; Mitchell, A.; Tonk, S.; Kuruva, C.S.; Bhatti, J.S.; Kandimalla, R.; Vijayan, M.; Kumar, S.; Wang, R.; Pradeepkiran, J.A.; Ogunmokun, G.; Thamarai, K.; Quesada, K.; Boles, A.; Reddy, A.P. Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease. J. Alzheimers Dis., 2018, 61(3), 843-866.
[http://dx.doi.org/10.3233/JAD-170512] [PMID: 29332042]
[11]
Aggarwal, B.B.; Deb, L.; Prasad, S. Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses. Molecules, 2014, 20(1), 185-205.
[http://dx.doi.org/10.3390/molecules20010185] [PMID: 25547723]
[12]
Prasad, S.; Tyagi, A.K.; Aggarwal, B.B. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: The golden pigment from golden spice. Cancer Res. Treat., 2014, 46(1), 2-18.
[http://dx.doi.org/10.4143/crt.2014.46.1.2] [PMID: 24520218]
[13]
Costa, C.; Moreira, J.N.; Amaral, M.H.; Sousa Lobo, J.M.; Silva, A.C. Nose-to-brain delivery of lipid based nanosystems for epileptic seizures and anxiety crisis. J. Control. Release, 2019, 295(295), 187-200.
[http://dx.doi.org/10.1016/j.jconrel.2018.12.049] [PMID: 30610952]
[14]
Schwarz, B.; Merkel, O.M. Nose to brain delivery of biologics. Ther. Deliv., 2019, 10(4), 207-210.
[http://dx.doi.org/10.4155/tde-2019-0013] [PMID: 30991920]
[15]
Kumar, R.; Gulati, M.; Singh, S.K.; Sharma, D.; Porwal, O. Road from nose to brain for treatment of Alzheimer: The bumps and humps. CNS Neurol. Disord. Drug Targets, 2020, 19(9), 663-675.
[http://dx.doi.org/10.2174/1871527319666200708124726] [PMID: 32640969]
[16]
Mittal, D.; Ali, A.; Md, S.; Baboota, S.; Sahni, J.K.; Ali, J. Insights into direct nose to brain delivery: Current status and future perspective. Drug Deliv., 2014, 21(2), 75-86.
[http://dx.doi.org/10.3109/10717544.2013.838713] [PMID: 24102636]
[17]
Espinoza, L.C.; Silva, A.M.; Clares, B.; Rodríguez, M.J.; Halbaut, L.; Cañas, M.A.; Calpena, A.C. Formulation strategies to improve nose to brain delivery of donepezil. Pharmaceutics, 2019, 11(2), 64.
[http://dx.doi.org/10.3390/pharmaceutics11020064] [PMID: 30717264]
[18]
Ahmed, T.A.; Badr-Eldina, S.M.; Ahmed, O.A.A.; Aldawsaria, H. Intranasal optimized solid lipid nanoparticles loaded in situ gel for enhancing trans-mucosal delivery of simvastatin. J. Drug Deliv. Sci. Technol., 2018, 48, 499-508.
[http://dx.doi.org/10.1016/j.jddst.2018.10.027]
[19]
Mukherjee, S.; Ray, S.; Thakur, R.S. Solid lipid nanoparticles: A modern formulation approach in drug delivery system. Indian J. Pharm. Sci., 2009, 71(4), 349-358.
[http://dx.doi.org/10.4103/0250-474X.57282] [PMID: 20502539]
[20]
Ekambaram, P.; Abdul, H.S. Formulation and evaluation of solid lipid nanoparticles of ramipril. J. Young Pharm., 2011, 3(3), 216-220.
[http://dx.doi.org/10.4103/0975-1483.83765] [PMID: 21897661]
[21]
Kesharwani, R.; Sachan, A.; Singh, S.; Pate, D. Formulation and evaluation of Solid Lipid Nanoparticle (SLN) based topical gel of etoricoxib. J. Appl. Pharm. Sci., 2016, 6(10), 124-131.
[http://dx.doi.org/10.7324/JAPS.2016.601017]
[22]
Bhatt, S.; Sharma, J.; Singh, M.; Saini, V. Solid lipid nanoparticles: A promising technology for delivery of poorly water soluble drugs. ACTA Pharm Sci., 2018, 56(3)
[http://dx.doi.org/10.23893/1307-2080.APS.05616]
[23]
Fatouh, A.M.; Elshafeey, A.H.; Abdelbary, A. Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: Formulation, optimization and in vivo pharmacokinetics. Drug Des. Devel. Ther., 2017, 11, 1815-1825.
[http://dx.doi.org/10.2147/DDDT.S102500] [PMID: 28684900]
[24]
Rapalli, V.K.; Kaul, V.; Gorantla, S.; Waghule, T.; Dubey, S.K.; Pandey, M.M.; Singhvi, G.UV Spectrophotometric method for characterization of curcumin loaded nanostructured lipid nanocarriers in simulated conditions: Method development, in-vitro and ex-vivo applications in topical delivery. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2020, 224, 117392.
[http://dx.doi.org/10.1016/j.saa.2019.117392] [PMID: 31330421]
[25]
Shi, L.; Li, Z.; Yu, L.; Jia, H.; Zheng, L. Effects of surfactants and lipids on the preparation of solid lipid nanoparticles using double emulsion method. J. Dispers. Sci. Technol., 2011, 32(2), 254-259.
[http://dx.doi.org/10.1080/01932691003659130]
[26]
Bhatt, H.; Rompicharla, S.V.K.; Komanduri, N.; Aashma, S.; Paradkar, S.; Ghosh, B.; Biswas, S. Development of curcumin-loaded solid lipid nanoparticles utilizing glyceryl monostearate as single lipid using QBD approach: Characterization and evaluation of anticancer activity against human breast cancer cell line. Curr. Drug Deliv., 2018, 15(9), 1271-1283.
[http://dx.doi.org/10.2174/1567201815666180503120113] [PMID: 29732970]
[27]
Al Asmari, A.K.; Ullah, Z.; Tariq, M.; Fatani, A. Preparation, characterization, and in vivo evaluation of intranasally administered liposomal formulation of donepezil. Drug Des. Devel. Ther., 2016, 10, 205-215.
[PMID: 26834457]
[28]
Kurakula, M.; Ahmed, O.A.A.; Fahmy, U.A.; Ahmed, T.A. Solid lipid nanoparticles for transdermal delivery of avanafil: Optimization, formulation, in-vitro and ex-vivo studies. J. Liposome Res., 2016, 26(4), 288-296.
[http://dx.doi.org/10.3109/08982104.2015.1117490] [PMID: 26784833]
[29]
Joshi, A.S.; Patel, H.S.; Belgamwar, V.S.; Agrawal, A.; Tekade, A.R. Solid lipid nanoparticles of ondansetron HCl for intranasal delivery: Development, optimization and evaluation. J. Mater. Sci. Mater. Med., 2012, 23(9), 2163-2175.
[http://dx.doi.org/10.1007/s10856-012-4702-7] [PMID: 22802103]
[30]
Shah, B.; Khunt, D.; Misra, M.; Padh, H. Application of Box-Behnken design for optimization and development of quetiapine fumarate loaded chitosan nanoparticles for brain delivery via intranasal route. Int. J. Biol. Macromol., 2016, 89, 206-218.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.04.076] [PMID: 27130654]
[31]
Bhatt, S.; Sharma, J.B.; Kamboj, R.; Kumar, M.; Saini, V.; Mandge, S. Design and optimization of febuxostat loaded nano lipid carriers using full factorial design. Turk. J. Pharm. Sci., 2021, 18(1), 61-67.
[http://dx.doi.org/10.4274/tjps.galenos.2019.32656] [PMID: 33633486]
[32]
Shah, B.; Khunt, D.; Bhatt, H.; Misra, M.; Padh, H. Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters. Eur. J. Pharm. Sci., 2015, 78(78), 54-66.
[http://dx.doi.org/10.1016/j.ejps.2015.07.002] [PMID: 26143262]
[33]
Tian, H.; Lu, Z.; Li, D.; Hu, J. Preparation and characterization of citral loaded solid lipid nanoparticles. Food Chem., 2018, 248, 78-85.
[http://dx.doi.org/10.1016/j.foodchem.2017.11.091] [PMID: 29329873]
[34]
Thakkar, H.P.; Desai, J.L.; Parmar, M.P. Application of Box-Behnken design for optimization of formulation parameters for nanostructured lipid carriers of candesartan cilexetil. Asian J. Pharm., 2014, 8(2), 81-89.
[http://dx.doi.org/10.4103/0973-8398.134921]
[35]
Sharma, J.B.; Bhatt, S.; Saini, V.; Kumar, M. Pharmacokinetics and pharmacodynamics of curcumin-loaded solid lipid nanoparticles in the management of streptozotocin-induced diabetes mellitus: Application of central composite design. Assay Drug Dev. Technol., 2021, 19(4), 262-279.
[http://dx.doi.org/10.1089/adt.2021.017] [PMID: 34000202]
[36]
Sharma, S.; Sharma, J.B.; Bhatt, S.; Kumar, M. Method development and validation of UV spectrophotometric method for the quantitative estimation of curcumin in simulated nasal fluid. Drug Res., 2020, 70(8), 356-359.
[http://dx.doi.org/10.1055/a-1193-4655] [PMID: 32575135]
[37]
Rana, S.S.; Bhatt, S.; Kumar, M.; Malik, A.; Sharma, J.B.; Arora, D.; Saini, V. Design and optimization of itraconazole loaded SLN for intranasal administration using central composite design. Nanosci. Nanotechnol. Asia, 2020, 10(6), 884-891.
[http://dx.doi.org/10.2174/2210681209666191111113112]

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