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Drug Delivery Letters

Editor-in-Chief

ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

Research Article

Self-micro Emulsifying Drug Delivery System “SMEDDS” for Efficient Oral Delivery of Andrographolide

Author(s): Sivaram Nallamolu*, Vijaya R. Jayanti, Mallikarjun Chitneni, Liew Y. Khoon and Prashant Kesharwani*

Volume 10, Issue 1, 2020

Page: [38 - 53] Pages: 16

DOI: 10.2174/2210303109666190723145209

Price: $65

Abstract

Objective: Andrographolide has potent anticancer and antimicrobial activity; however, its clinical application has been limited due to its poor water solubility as well as lack of appropriate formulation. The objective of this investigation was to formulate Self–Micro Emulsifying Drug Delivery System (SMEDDS) of andrographolide and explore its oral drug delivery aptitudes.

Methods: Andrographolide SMEDDS was optimized by ternary phase approach and studied for various in vitro characteristics: Particle size, electron microscopy, polydispersity index, surface charge, dilution effect, pH stability, freeze-thaw effect, dissolution profile and stability studies. Further, antimicrobial and cytotoxic performance of andrographolide SMEDDS were evaluated in MCF–7 breast cancer cell lines and methicillin-resistant microorganisms, respectively.

Results: An optimized SMEDDS formulation of andrographolide was successfully prepared and evaluated for its drug delivery potential. The solubility of andrographolide in the developed SMEDDS formulation was increased significantly, and the drug loading was enough for making this drug clinically applicable. The andrographolide SMEDDS formulation competitively inhibited the growth of microorganisms and showed enhanced anti–microbial activity against MRSA microorganisms.

Conclusions: The SMEDDS strategy represents one of the best approaches to deliver andrographolide via oral route, while resolving its solubility limitations.

Keywords: Andrographolide, SMEDDS, ternary phase optimization, solubilization, antimicrobial susceptibility, cytotoxicity potential.

Graphical Abstract

[1]
Chakravarti, R.N.; Chakravarti, D. Andrographolide, the active constituent of Andrographis paniculata Nees; a preliminary communication. Ind. Med. Gaz., 1951, 86, 96-97. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14860885
[2]
Singha, P.K.; Roy, S.; Dey, S. Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. J. Ethnopharmacol., 111, 13-21. [cited 2018 Feb 2] Available from: http://linkinghub.elsevier.com/retrieve/pii/S037887410600554X
[3]
Bothiraja, C.; Shinde, M.B.; Rajalakshmi, S.; Pawar, A.P. Evaluation of molecular pharmaceutical and in-vivo proper-ties of spraydried isolated andrographolide-PVP. J. Pharm. Pharmacol., 61, 1465-72. [cited 2018 Feb 2] Available from: http://doi.wiley.com/10.1211/jpp/61.11.0005
[4]
Nam, T.; Park, S.; Lee, S-Y.; Park, K.; Choi, K.; Song, I.C. Tumor Targeting Chitosan Nanoparticles for Dual-Modality Optical/MR Cancer Imaging. Bioconjug. Chem., 21, 578-582.
[5]
Abedini, F.; Ebrahimi, M.; Roozbehani, A.H.; Domb, A.J.; Hosseinkhani, H. Overview on natural hydrophilic polysaccharide polymers in drug delivery. Polym. Adv. Technol., 2018, 29(10), 2564-2573.
[http://dx.doi.org/10.1002/pat.4375]
[6]
Farokhi, M.; Mottaghitalab, F.; Shokrgozar, M.A.; Ou, K-L.; Mao, C.; Hosseinkhani, H. Importance of dual delivery systems for bone tissue engineer-ing J. Control. Release, 225, 152-69. Available from: https://linkinghub.elsevier.com/retrieve/pii/S016836591630030X
[7]
Mottaghitalab, F.; Farokhi, M.; Shokrgozar, M.A.; Atyabi, F.; Hosseinkhani, H. Silk fibroin nanoparticle as a novel drug delivery system J. Control. Release, 206, 161-76. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0168365915001868
[8]
Mottaghitalab, F.; Hosseinkhani, H.; Shokrgozar, M.A.; Mao, C.; Yang, M.; Farokhi, M. Silk as a potential candidate for bone tissue engineering. J. Control. Release , 215, 112-28. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0168365915300432
[9]
Khan, W.; Hosseinkhani, H.; Ickowicz, D.; Hong, P-D.; Yu, D-S.; Domb, A.J. Polysaccharide gene transfection agents., 2012. Available from: https://linkinghub.elsevier.com/retrieve/pii/S174270611200459X
[http://dx.doi.org/10.1016/j.actbio.2012.09.022]
[10]
Hosseinkhani, H.; Abedini, F.; Ou, K-L.; Domb, A.J. Polymers in gene therapy technology. Polym. Adv. Technol., 2015.
[http://dx.doi.org/10.1002/pat.3432]
[11]
Hosseinkhani, H.; Hong, P-D.; Yu, D-S. Self-Assembled Proteins and Peptides for Regenerative Medi-cine. Chem. Rev., 2013.
[http://dx.doi.org/10.1021/cr300131h]
[12]
Mahmoudi, M.; Hosseinkhani, H.; Hosseinkhani, M.; Boutry, S.; Simchi, A.; Journeay, W.S. Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advance-ment of clinical regenerative medicine. Chem. Rev., 111, 253-80. http://dx.doi.org/http://dx.doi.org/10.1021/cr1001832
[13]
Alibolandi, M.; Abnous, K.; Sadeghi, F.; Hosseinkhani, H.; Ramezani, M.; Hadizadeh, F. Folate receptor-targeted multimodal polymersomes for deliv-ery of quantum dots and doxorubicin to breast adenocarci-noma: In vitro and in vivo evaluation Int. J. Pharm., 500, 162-78. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26802496
[14]
Kesharwani, P.; Xie, L.; Banerjee, S.; Mao, G.; Padhye, S.; Sarkar, F.H. Hyaluronic acid-conjugated polyamidoamine dendrimers for targeted delivery of 3,4-difluorobenzylidene curcumin to CD44 overexpressing pancreatic cancer cells. Colloids Surf. B. Biointerfaces, 136, 413-23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26440757
[15]
Luong, D.; Kesharwani, P.; Killinger, B.A.; Moszczynska, A.; Sarkar, F.H.; Padhye, S.; Rishi, A.K.; Iyer, A.K. Solubility enhancement and targeted delivery of a potent anticancer flavonoid analogue to cancer cells using ligand decorated dendrimer nano-architectures. J. Colloid Interface Sci., 2016, 484, 33-43.
[http://dx.doi.org/10.1016/j.jcis.2016.08.061] [PMID: 27585998]
[16]
Kesharwani, P.; Banerjee, S.; Padhye, S.; Sarkar, F.H.; Iyer, A.K. Hyaluronic Acid Engineered Nanomicelles Loaded with 3,4-Difluorobenzylidene Curcumin for Targeted Killing of CD44+ Stem-Like Pancreatic Cancer Cells. Biomacromolecules, 2015, 16(9), 3042-3053.
[http://dx.doi.org/10.1021/acs.biomac.5b00941] [PMID: 26302089]
[17]
Kesharwani, P.; Banerjee, S.; Padhye, S.; Sarkar, F.H.; Iyer, A.K. Parenterally administrable nano-micelles of 3, 4- difluorobenzylidene curcumin for treating pancreatic cancers. Colloids Surfaces B Biointerfaces, Available from: http://www.sciencedirect.com/science/article/pii/S0927776515003045
[18]
Soni, N.; Soni, N.; Pandey, H.; Maheshwari, R.; Kesharwani, P.; Tekade, R.K. Augmented delivery of gemcitabine in lung cancer cells exploring mannose anchored solid lipid nanoparticles. J. Colloid Interface Sci., 2016, 481, 107-116.
[http://dx.doi.org/10.1016/j.jcis.2016.07.020] [PMID: 27459173]
[19]
Kesharwani, P.; Jain, A.; Jain, A.; Jain, A.K.; Garg, N.K.; Tekade, R.K. Cationic bovine serum albumin (CBA) conjugated poly lactic: Co -glycolic acid (PLGA) nanoparticles for extended delivery of methotrexate into brain tumors; RSC Adv, 2016, p. 6.
[20]
Ng, K.E.; Amin, M.C.I.M.; Katas, H.; Amjad, M.W.; Butt, A.M.; Kesharwani, P.; Iyer, A.K. pH-Responsive Triblock Copolymeric Micelles Decorated with a Cell-Penetrating Peptide Provide Efficient Doxorubicin Delivery. Nanoscale Res. Lett., 2016, 11(1), 539.
[http://dx.doi.org/10.1186/s11671-016-1755-4] [PMID: 27921280]
[21]
Tiwari, A.; Kesharwani, P.; Gajbhiye, V.; Jain, N.K. Synthesis and characterization of dendro-PLGA nanoconjugate for protein stabilization. Colloids Surf. B Biointerfaces, 2015, 134, 279-286.
[http://dx.doi.org/10.1016/j.colsurfb.2015.06.064] [PMID: 26209778]
[22]
Singh, R.; Kesharwani, P.; Mehra, N.K.; Singh, S.; Banerjee, S.; Jain, N.K. Development and characterization of folate anchored Saquinavir entrapped PLGA nanoparticles for anti-tumor activity. Drug Dev. Ind. Pharm., 2015, 41(11), 1888-1901.
[http://dx.doi.org/10.3109/03639045.2015.1019355] [PMID: 25738812]
[23]
Kesharwani, P.; Tekade, R.K.; Jain, N.K. Generation dependent safety and efficacy of folic acid conjugated dendrimer based anticancer drug formulations. Pharm. Res., 2015, 32(4), 1438-1450.
[http://dx.doi.org/10.1007/s11095-014-1549-2] [PMID: 25330744]
[24]
Jain, A.; Kesharwani, P.; Garg, N.K.; Jain, A.; Jain, S.A.; Jain, A.K.; Nirbhavane, P.; Ghanghoria, R.; Tyagi, R.K.; Katare, O.P. Galactose engineered solid lipid nanoparticles for targeted delivery of doxorubicin. Colloids Surf. B Biointerfaces, 2015, 134, 47-58.
[http://dx.doi.org/10.1016/j.colsurfb.2015.06.027] [PMID: 26142628]
[25]
Zeeshan, F.; Tabbassum, M.; Kesharwani, P. Investigation on Secondary Structure Alterations of Protein Drugs as an Indicator of Their Biological Activity Upon Thermal Exposure., 2019.
[http://dx.doi.org/10.1007/s10930-019-09837-4]
[26]
Choudhury, H.; Pandey, M.; Yin, T.H.; Kaur, T.; Jia, G.W.; Tan, S.Q.L.; Weijie, H.; Yang, E.K.S.; Keat, C.G.; Bhattamishra, S.K.; Kesharwani, P.; Md, S.; Molugulu, N.; Pichika, M.R.; Gorain, B. Rising horizon in circumventing multidrug resistance in chemotherapy with nanotechnology. Mater. Sci. Eng. C, 2019, 101, 596-613.
[http://dx.doi.org/10.1016/j.msec.2019.04.005] [PMID: 31029353]
[27]
Kesharwani, P.; Choudhury, H.; Meher, J.G.; Pandey, M.; Gorain, B. Dendrimer-entrapped gold nanoparticles as promising nanocarriers for anticancer therapeutics and imaging., 2019. Available from: https://www.sciencedirect.com/science/article/pii/S007964251930026X
[http://dx.doi.org/10.1016/j.pmatsci.2019.03.003]
[28]
Tripathi, P.K.; Gorain, B.; Choudhury, H.; Srivastava, A.; Kesharwani, P. Dendrimer entrapped microsponge gel of dithranol for effective topical treatment., 2019. Available from: https://www.sciencedirect.com/science/article/pii/S240584401834413X
[http://dx.doi.org/10.1016/j.heliyon.2019.e01343]
[29]
Pandey, D.; Kesharwani, P.; Jain, D. Entrapment of drug-sorbate complex in submicron emulsion: A potential approach to improve antimicrobial activity in bac-terial corneal infection J. Drug Deliv. Sci. Technol., 49, 455-62. Available from: https://www.sciencedirect.com/science/article/pii/S1773224718306415
[30]
Gorain, B.; Choudhury, H.; Pandey, M.; Nair, A.B.; Iqbal Mohd Amin, M.C.; Molugulu, N. Dendrimer-Based Nanocarriers in Lung Cancer Therapy., 2019.
[http://dx.doi.org/10.1016/B978-0-12-815720-6.00007-1 ]
[31]
Solè, I.; Pey, C.M.; Maestro, A.; González, C.; Porras, M.; Solans, C.; Gutiérrez, J.M. Nano-emulsions prepared by the phase inversion composition method: preparation variables and scale up. J. Colloid Interface Sci., 2010, 344(2), 417-423.
[http://dx.doi.org/10.1016/j.jcis.2009.11.046] [PMID: 20129612]
[32]
Tekade, R.K.; D’Emanuele, A.; Elhissi, A.; Agrawal, A.; Jain, A.; Arafat, B.T. Extraction and RP-HPLC determination of taxol in rat plasma, cell culture and quality control samples J. Biomed. Res., 27, 394-405. Available from:http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR130507&flag=1
[33]
Rhee, Y-S.; Choi, J-G.; Park, E-S.; Chi, S-C. Transdermal delivery of ketoprofen using microemulsions. Int. J. Pharm., 2001, 228(1-2), 161-170.
[http://dx.doi.org/10.1016/S0378-5173(01)00827-4] [PMID: 11576778]
[34]
Müller, B.W.; Müller, R.H. Particle size distributions and particle size alterations in mi-croemulsions. J. Pharm. Sci. , 73, 919-22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6470953
[35]
Tandel, H.; Raval, K.; Nayani, A.; Upadhay, M. Preparation and evaluation of cilnidipine microemulsion J. Pharm. Bioallied Sci. , 4, S114-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23066184
[36]
Choudhury, H.; Pandey, M.; Gorain, B.; Chatterjee, B.; Madheswaran, T.; Md, S. Nanoemulsions as Effective Carriers for the Treatment of Lung Cancer., 2019.
[http://dx.doi.org/10.1016/B978-0-12-815720-6.00009-5]
[37]
Gorain, B.; Bhattamishra, S.K.; Choudhury, H.; Nandi, U.; Pandey, M. Overexpressed Receptors and Proteins in Lung Cancer., 2019.
[http://dx.doi.org/10.1016/B978-0-12-815720-6.00003-4]
[38]
Kesharwani, P.; Tekade, R.K.; Jain, N.K. Formulation development and in vitro-in vivo assessment of the fourth-generation PPI dendrimer as a cancer-targeting vector., 2014. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24593000
[39]
Kesharwani, P.; Tekade, R.K.; Gajbhiye, V.; Jain, K.; Jain, N.K. Cancer targeting potential of some ligand-anchored poly(propylene imine) dendrimers: a comparison. Nanomedicine (Lond.), 2011, 7(3), 295-304.
[http://dx.doi.org/10.1016/j.nano.2010.10.010] [PMID: 21070888]
[40]
Dwivedi, N.; Shah, J.; Mishra, V.; Tambuwala, M.; Kesharwani, P. Nanoneuromedicine for management of neurodegenerative disorder J. Drug Deliv. Sci. Technol. , 49, 477-90. Available from: https://www.sciencedirect.com/science/article/pii/S1773224718313716
[41]
Attama, A.A.; Nkemnele, M.O. In vitro evaluation of drug release from self micro-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus., 2005. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0378517305005697
[http://dx.doi.org/10.1016/j.ijpharm.2005.08.018]
[42]
Wei, L.; Sun, P.; Nie, S.; Pan, W. Preparation and Evaluation of SEDDS and SMEDDS Containing Carvedilol., 2005. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16221613
[http://dx.doi.org/10.1080/03639040500216428]
[43]
Sprunk, A.; Strachan, C.J.; Graf, A. Rational formulation development and in vitro assessment of SMEDDS for oral delivery of poorly water soluble drugs., 2012. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0928098712001704
[http://dx.doi.org/10.1016/j.ejps.2012.04.001]
[44]
Singh, A.K.; Chaurasiya, A.; Singh, M.; Upadhyay, S.C.; Mukherjee, R.; Khar, R.K. Exemestane loaded self-microemulsifying drug delivery sys-tem (SMEDDS): development and optimization. AAPS PharmSciTech, 9, 628-34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18473177
[45]
Khurana, R.K.; Beg, S.; Burrow, A.J.; Vashishta, R.K.; Katare, O.P.; Kaur, S.; Kesharwani, P.; Singh, K.K.; Singh, B. Enhancing biopharmaceutical performance of an anticancer drug by long chain PUFA based self-nanoemulsifying lipidic nanomicellar systems. Eur. J. Pharm. Biopharm., 2017, 121, 42-60.
[http://dx.doi.org/10.1016/j.ejpb.2017.09.001] [PMID: 28887099]
[46]
Madheswaran, T.; Baskaran, R.; Yoo, B.K.; Kesharwani, P. In vitro and in vivo skin distribution of 5α-reductase inhibitors loaded into liquid crystalline nanoparticles. J. Pharm. Sci., 2017, 106(11), 3385-3394.
[http://dx.doi.org/10.1016/j.xphs.2017.06.016] [PMID: 28652158]
[47]
Shringirishi, M.; Mahor, A.; Gupta, R.; Prajapati, S.K.; Bansal, K.; Kesharwani, P. Fabrication and characterization of nifedipine loaded β-cyclodextrin nanosponges: An in vitro and in vivo evaluation. J. Drug Deliv. Sci. Technol., 2017, 41
[http://dx.doi.org/10.1016/j.jddst.2017.08.005]
[48]
Bothiraja, C.; Shinde, M.B.; Rajalakshmi, S.; Pawar, A.P. Evaluation of molecular pharmaceutical and in-vivo proper-ties of spraydried isolated andrographolide-PVP J. Pharm. Pharmacol. , 61, 1465-72. Available from:
[http://dx.doi.org/10.1211/jpp/ 61.11.0005]
[49]
Calabrese, C.; Berman, S.H.; Babish, J.G.; Ma, X.; Shinto, L.; Dorr, M. A phase I trial of andrographolide in HIV positive patients and normal volunteers., 2000. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10925397
[http://dx.doi.org/10.1002/1099-1573(200008)14:5❬333::AIDPTR584❭ 3.0.CO;2-D]
[50]
Panossian, A.; Hovhannisyan, A.; Mamikonyan, G.; Abrahamian, H.; Hambardzumyan, E.; Gabrielian, E. Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human., 2000.
[http://dx.doi.org/10.1016/S0944-7113(00)80054-9]
[51]
Khan, I.; Kumar, H.; Mishra, G.; Gothwal, A.; Kesharwani, P.; Gupta, U. Polymeric Nanocarriers: A New Horizon for the Effective Management of Breast Cancer., 2017. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28875848
[52]
Jain, A.; Sharma, G.; Kushwah, V.; Garg, N.K.; Kesharwani, P.; Ghoshal, G.; Singh, B.; Shivhare, U.S.; Jain, S.; Katare, O.P. Methotrexate and beta-carotene loaded-lipid polymer hybrid nanoparticles: a preclinical study for breast cancer. Nanomedicine (Lond.), 2017, 12(15), 1851-1872.
[http://dx.doi.org/10.2217/nnm-2017-0011] [PMID: 28703643]

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