Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Research Article

Preparation, Characterization and In Vitro Antioxidant Potential of Boldine-phospholipid Complex

Author(s): Arun Kumar Singh and Anita Singh*

Volume 16, Issue 1, 2021

Published on: 21 October, 2020

Page: [89 - 99] Pages: 11

DOI: 10.2174/1574885515999201021165556

Price: $65

Abstract

Background: Boldine, is an aporphine alkaloid that possesses potent antioxidant activity. Despite having enormous potential, the clinical application of boldine was restricted because of its poor bioavailability attributed to its poor aqueous solubility and rapid clearance from the body. The drug phospholipid complexation techniques were frequently employed to overcome the limitation of low bioavailability of phytoconstituents/herbal extract.

Objective: The boldine phospholipid complex (BOL-PC) formulation was developed for enhancing antioxidant potential of boldine by preparing its phospholipid complex.

Methods: Boldine loaded phospholipid (BOL-PC) complex was prepared by refluxing followed by solvent evaporation method and subjected to various physicochemical and spectral analysis. Further, the in-vitro antioxidant activity was evaluated by DPPH free radical scavenging method.

Results: The formation of the complex was confirmed by 1H NMR and thermal analysis. SEM and PXRD revealed partial amorphization of drug in complex formed. The BOL-PC dissolution rate and solubility were significantly improved compared to the parent compound. The maximum % yield and % EE were found to be 95.92± 0.01732 and 95.89±0.3502 respectively in the optimized formulation (F3), which exhibited concentration-dependent antioxidant property.

Conclusion: It was concluded from the study that the phospholipid complexation of boldine has better antioxidant potential and improved the solubility, dissolution profile which may facilitate its oral absorption and enhances its chances for clinical application.

Keywords: Phyto-phospholipid complex, boldine, PXRD, solubility, antioxidant activity, DSC.

« Previous
Graphical Abstract
[1]
Teng Z, Yuan C, Zhang F, et al. Intestinal absorption and first-pass metabolism of polyphenol compounds in rat and their transport dynamics in Caco-2 cells. PLoS One 2012; 7(1)e29647
[http://dx.doi.org/10.1371/journal.pone.0029647] [PMID: 22253753]
[2]
Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004; 79(5): 727-47.
[http://dx.doi.org/10.1093/ajcn/79.5.727] [PMID: 15113710]
[3]
Bhattacharya S. Phytosomes: the new technology for enhancement of bioavailability of botanicals and nutraceuticals. Intl J Health Res 2009; 2(3): 225-32.
[http://dx.doi.org/10.4314/ijhr.v2i3.47905]
[4]
Kidd P, Head K. A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos). Altern Med Rev 2005; 10(3): 193-203.
[PMID: 16164374]
[5]
Montes M, Wilkomirsky T, Eds. Medicina tradicional chilena: Universidad de Concepción, Concepción, Chile 1985.
[6]
O’Brien P, Carrasco-Pozo C, Speisky H. Boldine and its antioxidant or health-promoting properties. Chem Biol Interact 2006; 159(1): 1-17.
[http://dx.doi.org/10.1016/j.cbi.2005.09.002] [PMID: 16221469]
[7]
Jang YY, Song JH, Shin YK, Han ES, Lee CS. Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats. Pharmacol Res 2000; 42(4): 361-71.
[http://dx.doi.org/10.1006/phrs.2000.0705] [PMID: 10987997]
[8]
Lanhers MC, Joyeux M, Soulimani R, et al. Hepatoprotective and anti-inflammatory effects of a traditional medicinal plant of Chile, Peumus boldus. Planta Med 1991; 57(2): 110-5.
[http://dx.doi.org/10.1055/s-2006-960043] [PMID: 1891491]
[9]
Cermanova J, Prasnicka A, Dolezelova E, et al. Pharmacokinetics of boldine in control and Mrp2-deficient rats. Physiol Res 2016; 65(Suppl. 4): S489-97.
[http://dx.doi.org/10.33549/physiolres.933520] [PMID: 28006931]
[10]
Jiménez I, Speisky H. Biological disposition of boldine: in vitro and in vivo studies. Phytother Res 2000; 14(4): 254-60.
[http://dx.doi.org/10.1002/1099-1573(200006)14:4<254:AID-PTR582>3.0.CO;2-M] [PMID: 10861968]
[11]
Lu W, Kelly AL, Miao S. Emulsion-based encapsulation and delivery systems for polyphenols. Trends Food Sci Technol 2016; 47: 1-9.
[http://dx.doi.org/10.1016/j.tifs.2015.10.015]
[12]
Munin A, Edwards-Lévy F. Encapsulation of natural polyphenolic compounds; a review. Pharmaceutics 2011; 3(4): 793-829.
[http://dx.doi.org/10.3390/pharmaceutics3040793 ] [PMID: 24309309]
[13]
He J, Luo L, Zeng L. Recent advances in research on preparation technologies and applications of tea polyphenol nanoparticles. Shipin Kexue 2011; 32: 317-22.
[14]
Lambert JD, Sang S, Hong J, et al. Peracetylation as a means of enhancing in vitro bioactivity and bioavailability of epigallocatechin-3-gallate. Drug Metab Dispos 2006; 34(12): 2111-6.
[http://dx.doi.org/10.1124/dmd.106.011460] [PMID: 16997910]
[15]
Mulholland PJ, Ferry DR, Anderson D, et al. Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin. Ann Oncol 2001; 12(2): 245-8.
[http://dx.doi.org/10.1023/A:1008372017097] [PMID: 11300332]
[16]
Chen ZP, Sun J, Chen HX, et al. Comparative pharmacokinetics and bioavailability studies of quercetin, kaempferol and isorhamnetin after oral administration of Ginkgo biloba extracts, Ginkgo biloba extract phospholipid complexes and Ginkgo biloba extract solid dispersions in rats. Fitoterapia 2010; 81(8): 1045-52.
[http://dx.doi.org/10.1016/j.fitote.2010.06.028] [PMID: 20603197]
[17]
Khan J, Alexander A. Ajazuddin, Saraf S, Saraf S. Recent advances and future prospects of phyto-phospholipid complexation technique for improving pharmacokinetic profile of plant actives. J Control Release 2013; 168(1): 50-60.
[http://dx.doi.org/10.1016/j.jconrel.2013.02.025] [PMID: 23474031]
[18]
Kidd PM. Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts. Altern Med Rev 2009; 14(3): 226-46.
[PMID: 19803548]
[19]
Loguercio C, Andreone P, Brisc C, et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic Biol Med 2012; 52(9): 1658-65.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.02.008 ] [PMID: 22343419]
[20]
Saoji SD, Raut NA, Dhore PW, Borkar CD, Popielarczyk M, Dave VS. Preparation and evaluation of phospholipid-based complex of standardized centella extract (SCE) for the enhanced delivery of phytoconstituents. AAPS J 2016; 18(1): 102-14.
[http://dx.doi.org/10.1208/s12248-015-9837-2] [PMID: 26563253]
[21]
Telange DR, Nirgulkar SB, Umekar MJ, Patil AT, Pethe AM, Bali NR. Enhanced transdermal permeation and anti-inflammatory potential of phospholipids complex-loaded matrix film of umbelliferone: Formulation development, physico-chemical and functional characterization. Eur J Pharm Sci 2019; 131: 23-38.
[http://dx.doi.org/10.1016/j.ejps.2019.02.006] [PMID: 30735820]
[22]
Agarwal A, Kharb V, Saharan VA. Process optimisation, characterisation and evaluation of resveratrol-phospholipid complexes using Box-Behnken statistical design. Int Curr Pharm J 2014; 3(7): 301-8.
[http://dx.doi.org/10.3329/icpj.v3i7.19079]
[23]
Gupta PS, Sharma V, Pathak K. Melt sonocrystallized piroxicam for oral delivery: particle characterization, solid state analysis, and pharmacokinetics. Expert Opin Drug Deliv 2013; 10(1): 17-32.
[http://dx.doi.org/10.1517/17425247.2013.736961 ] [PMID: 23102052]
[24]
Udapurkar PP, Bhusnure OG, Kamble SR. Diosmin phytosomes: development, optimization and physicochemical characterization. Indian J Pharma Edu Res 2018; 52(4): s29-36.
[25]
Cheng W, Li X, Zhang C, Chen W, Yuan H, Xu S. Preparation and in vivo-in vitro evaluation of polydatin-phospholipid complex with improved dissolution and bioavailability. Int J Drug Dev Res 2017; 9: 39-43.
[26]
Mondal R, Bobde Y, Ghosh B, Giri T. Development and characterization of a phospholipid complex for effective delivery of capsaicin. Indian J Pharm Sci 2019; 81(6): 1011-9.
[27]
Dave V, Telange D, Wavare K, Umekar M, Anand S, Patil A. Drug-phospholipid complex-loaded matrix film formulation for the enhanced transdermal delivery of quercetin. J Excip Food Chem 2018; 9(2): 3718.
[28]
Telange DR, Patil AT, Pethe AM, Tatode AA, Anand S, Dave VS. Kaempferol-phospholipid complex: formulation, and evaluation of improved solubility, in vivo bioavailability, and antioxidant potential of kaempferol. J Excip Food Chem 2016; 7(4): 1174.
[29]
Singh D, Rawat M, Semalty A, Semalty M. Emodin-phospholipid complex. J Therm Anal Calorim 2012; 108(1): 289-98.
[http://dx.doi.org/10.1007/s10973-011-1759-3]
[30]
Habbu P, Madagundi S, Shastry R, Vanakudri R, Kulkarni V. Preparation and evaluation of antidiabetic activity of allium cepa-phospholipid complex (phytosome) in streptozotocin induced diabetic rats. RGUHS J Pharm Sci 2015; 5(4): 132-41.
[http://dx.doi.org/10.5530/rjps.2015.4.3]
[31]
Alhakamy NA, Fahmy AU, Badr-Eldin SM, et al. Optimized icariin phytosomes exhibit enhanced cytotoxicity and apoptosis-inducing activities in ovarian cancer cells. Pharmaceutics 2020; 12(4): 346.
[http://dx.doi.org/10.3390/pharmaceutics12040346 ] [PMID: 32290412]
[32]
Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. Lebensm Wiss Technol 1995; 28(1): 25-30.
[http://dx.doi.org/10.1016/S0023-6438(95)80008-5]
[33]
Mensor LL, Menezes FS, Leitão GG, et al. Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytother Res 2001; 15(2): 127-30.
[http://dx.doi.org/10.1002/ptr.687] [PMID: 11268111]
[34]
Deepalakshmi K, Mirunalini S, Krishnaveni M, Arulmozhi V. In vitro and in vivo antioxidant potentials of an ethanolic extract of Ganoderma lucidum in rat mammary carcinogenesis. Chin J Nat Med 2013; 11(6): 621-7.
[http://dx.doi.org/10.1016/S1875-5364(13)60072-2 ] [PMID: 24345503]
[35]
Pathan RA, Bhandari U. Preparation & characterization of embelin-phospholipid complex as effective drug delivery tool. J Incl Phenom Macrocycl Chem 2011; 69(1-2): 139-47.
[http://dx.doi.org/10.1007/s10847-010-9824-2]
[36]
Bombardelli E. Pharmaceutical and cosmetic compositions containing complexes of flavanolignans with phospholipids. Google Patents 1990.
[37]
Yue P-F, Yuan H-L, Li X-Y, Yang M, Zhu W-F. Process optimization, characterization and evaluation in vivo of oxymatrine-phospholipid complex. Int J Pharm 2010; 387(1-2): 139-46.
[http://dx.doi.org/10.1016/j.ijpharm.2009.12.008] [PMID: 20005937]
[38]
Maryana W, Rachmawati H, Mudhakir D. Formation of phytosome containing silymarin using thin layer-hydration technique aimed for oral delivery. Mat Tod Proc 2016; 3(3): 855-66.
[39]
Yue P-F, Yuan H-L, Li X, Yang M, Zhu W. Preparation, characterization and pharmacokinetics in vivo of oxymatrine-phospholipid complex. J Bioequiv Availab 2009; 1: 99-102.
[40]
Lu M, Qiu Q, Luo X, et al. Phyto-phospholipid complexes (phytosomes): A novel strategy to improve the bioavailability of active constituents. Asian J Pharm Sci 2019; 14(3): 265-74.
[http://dx.doi.org/10.1016/j.ajps.2018.05.011] [PMID: 32104457]
[41]
Singh D, Rawat M, Semalty A, Semalty M. Chrysophanol-phospholipid complex. J Therm Anal Calorim 2013; 111(3): 2069-77.
[http://dx.doi.org/10.1007/s10973-012-2448-6]
[42]
Xia HJ, Zhang ZH, Jin X, Hu Q, Chen XY, Jia XB. A novel drug-phospholipid complex enriched with micelles: preparation and evaluation in vitro and in vivo. Int J Nanomedicine 2013; 8: 545-54.
[http://dx.doi.org/10.2147/IJN.S39526] [PMID: 23431115]
[43]
Zhang J, Tang Q, Xu X, Li N. Development and evaluation of a novel phytosome-loaded chitosan microsphere system for curcumin delivery. Int J Pharm 2013; 448(1): 168-74.
[http://dx.doi.org/10.1016/j.ijpharm.2013.03.021] [PMID: 23524117]
[44]
Skoog DA, Holler FJ, Crouch SR. Principles of instrumental analysis: Cengage learning 2017.
[45]
D’souza SL, Deshmukh B, Bhamore JR, Rawat KA, Lenka N, Kailasa SK. Synthesis of fluorescent nitrogen-doped carbon dots from dried shrimps for cell imaging and boldine drug delivery system. RSC Advances 2016; 6(15): 12169-79.
[http://dx.doi.org/10.1039/C5RA24621K]
[46]
Semalty A, Semalty M, Singh D, Rawat M. Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery. J Incl Phenom Macrocycl Chem 2010; 67(3-4): 253-60.
[http://dx.doi.org/10.1007/s10847-009-9705-8]
[47]
Semalty A, Semalty M, Singh D, Rawat M. Phyto-phospholipid complex of catechin in value added herbal drug delivery. J Incl Phenom Macrocycl Chem 2012; 73(1-4): 377-86.
[http://dx.doi.org/10.1007/s10847-011-0074-8]
[48]
Yanyu X, Yunmei S, Zhipeng C, Qineng P. The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats. Int J Pharm 2006; 307(1): 77-82.
[http://dx.doi.org/10.1016/j.ijpharm.2005.10.001] [PMID: 16300915]
[49]
Lasonder E, Weringa WD. An NMR and DSC study of the interaction of phospholipid vesicles with some anti-inflammatory agents. J Colloid Interface Sci 1990; 139(2): 469-78.
[http://dx.doi.org/10.1016/0021-9797(90)90119-9]
[50]
Jena SK, Singh C, Dora CP, Suresh S. Development of tamoxifen-phospholipid complex: novel approach for improving solubility and bioavailability. Int J Pharm 2014; 473(1-2): 1-9.
[http://dx.doi.org/10.1016/j.ijpharm.2014.06.056] [PMID: 24992316]
[51]
Singh C, Bhatt TD, Gill MS, Suresh S. Novel rifampicin-phospholipid complex for tubercular therapy: synthesis, physicochemical characterization and in-vivo evaluation. Int J Pharm 2014; 460(1-2): 220-7.
[http://dx.doi.org/10.1016/j.ijpharm.2013.10.043] [PMID: 24188983]
[52]
Perrut M, Jung J, Leboeuf F. Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes. Part I: Micronization of neat particles. Int J Pharm 2005; 288(1): 3-10.
[http://dx.doi.org/10.1016/j.ijpharm.2004.09.007] [PMID: 15607252]
[53]
Soares JR, Dinis TC, Cunha AP, Almeida LM. Antioxidant activities of some extracts of Thymus zygis. Free Radic Res 1997; 26(5): 469-78.
[http://dx.doi.org/10.3109/10715769709084484] [PMID: 9179593]
[54]
Semalty A, Semalty M, Rawat MSM, Franceschi F. Supramolecular phospholipids-polyphenolics interactions: the PHYTOSOME strategy to improve the bioavailability of phytochemicals. Fitoterapia 2010; 81(5): 306-14.
[http://dx.doi.org/10.1016/j.fitote.2009.11.001] [PMID: 19919847]

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