Double-loaded liposomes encapsulating Quercetin and Quercetin beta-cyclodextrin complexes: Preparation, characterization and evaluation
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Abstract
using phosphatidylcholine and cholesterol were prepared and optimized. Factors such as ratio of lipids employed, drug:lipid ratio, etc. were fine tuned and optimized to achieve maximum entrapment of the Quercetin into the bilayer. Entrapment was further enhanced by double loading the liposomes. These were prepared by incorporating Quercetin as a plain drug as well as the inclusion complexes within the lipid bilayer and the aqueous compartment, respectively, of the liposomes using the thin film hydration technique. The highest entrapment was achieved with a lipid ratio of 9:1, and the amount of plain
drug entering the bilayer was 1/10th the amount of lipid employed. Double loading increased this value to one part of drug per five parts of lipid when Quercetin–beta-CD (1:1 mol/mol) was entrapped. The release of Quercetin from liposomes was highest when the drug was entrapped in the form of a complex with beta cylodextrin. The high entrapment ability of Quercetin in the form of plain drug as well as beta cylodextrin–Quercetin complexes in comparison with plain drug is an indubitable advantage of this approach.
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References
Lasic DD. Liposomes: From Physics to Applications. Amsterdam/ London,New York, Tokyo: Elsevier; 1993.
Schnyer A, Huwyler J. Drug transport to brain with targeted liposomes.
J Am Soc Exp Neurother 2005;2:99-107.
Brandl M. Liposomes as drug carriers: A technological approach.
Biotechnol Annu Rev 2001;7:59-85.
Gilbert BE, Wyde PR, Wilson SZ, Robins RK. Aerosol and intraperitoneal
administration of ribavirin and ribavirin triacetate: Pharmacokinetics
and protection of mice against intracerebral infection with influenza
A/WSN virus. Antimicrob Agents Chemother 1991;35:1448-53.
Garg M, Dutta T, Jain N. Reduced hepatic toxicity, enhanced cellular
uptake and altered pharmacokinetics of stavudine loaded galactosylated
Liposomes. Eu J Pharm Biopharm 2007;67:76-85.
Gulati M, Grover M, Singh S, Singh M. Lipophilic drug derivatives in
liposomes. Int J Pharm 1998;165:129-68.
Gregoriadis G. Liposome technology. 2nd ed. Vol. 1-2. Boca Raton, FL:
CRC Press; 1993.
McCormack B, Gregoriadis G. Drugs-in-cyclodextrins-in liposomes:
A novel concept in drug delivery. Int J Pharm 1994;112:249-58.
McCormack B, Gregoriadis G. Entrapment of cyclodextrin-drug
complexes into liposomes: Potential advantages in drug delivery. J Drug
Target 1994;2:449-54.
Hedges AR. Industrial Applications of Cyclodextrins. Chem Rev
;98:2035-44.
McCormack B, Gregoriadis G. Drugs-in-cyclodextrins-in-liposomes: An
approach to controlling the fate of water insoluble drugs in vivo. Int J
Pharm 1998;162:59-69.
Choi J, James Ou JH. Mechanisms of Liver Injury. III. Oxidative stress in the pathogenesis of hepatitis C virus. Am J Physiol Gastrointest Liver
Physiol 2006;290:847-51.
Davies KJ. Oxidative stress: The paradox of aerobic life. Biochem Soc
Symp 1995;61:1-31.
Lakhanpal P, Rai D. Quercetin: A versatile flavonoid. Internet J Med
Update 2007;2:22-37.
Mulholland PJ, Ferry DR, Anderson D, Hussain SA, Young AM, Cook JE,
et al. Pre-clinical and clinical study of QC12, a water-soluble, pro-drug
of quercetin. Ann Oncol 2001;12:245-8.
Gao Y, Wanga Y, Mab Y, Yua A, Caia F, Shaoa W, et al. Formulation
optimization and in situ absorption in rat intestinal tract of quercetin-
loaded microemulsion. Coll Surf B 2009;71:306-14.
Ader P, Wessmann A, Wolffram S. Bioavailability and metabolism of the
flavonol quercetin in the pig. Free Radic Biol Med 2000;28:1056-67.
Zhao L, Shi Y, Zou S, Sun M, Li L, Zhai G. Formulation and In Vitro
evaluation of quercetin loaded polymeric micelles composed of pluronic
P123 and D-a-tocopheryl polyethylene glycol succinate. J Biomed
Nanotechnol 2011;7:358-65.
Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions
across the lamellae of swollen phospholipids. J Mol Biol 1965;13:238- 25
Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Inst
;4:117-212.
Kurozumi M, Nambu N, Nagai T. Inclusion compounds of non-steroidal
antiinflammatory and other slightly water soluble drugs with α-and
β-Cyclodextrins in powdered form. Chem Pharm Bull 1975;23:3062-8.
New R. Introduction. In: New R, editor. Liposomes a practical approach.
st ed. Oxford: Oxford University Press; 1990. p. 1-32.
Gordon MH, Roedig-Penman A. Antioxidant activity of Quercetin and
myricetin in liposomes. Chem Phys Lipids 1998;97:79-85.
Maestrelli F, Gonzalez-Rodriguez ML, Rabasco AM, Mura P. Effect of
preparation technique on the properties of liposomes encapsulating
ketoprofen–cyclodextrin complexes aimed for transdermal delivery.
Int J Pharm 2006;312:53-60.
Ruozi B, Tosi G, Forni F, Vandelli AM. Ketorolac Tromethamine
Liposomes: Encapsulation and Release Studies. J Liposome Res
;15:175-85.
Mishra RK, Singhal GS. Calcium and magnesium induced changes
in the relative fluidity of phosphatidylcholine liposomes. J Biosci
;15:193- 7.
Henriksen I, Sande SA, Smistad G, Agren T, Karlsen J. In vitro evaluation
of drug release kinetics from liposomes by fractional dialysis. Int J Pharm
;119:231-8.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxide in animal tissue
by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
Tayade P, Kale R. Study of freeze-dried quercetin–cyclodextrin binary
systems by DSC, FT-IR, X-ray diffraction and SEM analysis. J Pharm
Biomed Anal 2004;34:333-9.
Kim KH, Frank MJ, Henderson NL. Application of differential scanning
calorimetry to the study of solid dispersions. J Pharm Sci 1985;74:283-9.
Ficarra R, Tommasini S, Raneri D, Calabrò ML, Di Bella MR, Rustichelli
C, et al. Study of flavonoids/β-cyclodextrins inclusion complexes
by NMR, FT-IR, DSC, X-ray investigation. J Pharm Biomed Anal
;29:1005-14.
Bhalerao SS, Harshal AR. Preparation, Optimization, Characterization,
and Stability Studies of Salicylic Acid Liposomes. Drug Develop Indus
Pharm 2003;29:451-67.
Terao J, Piskula MK. Flavonoids and membrane lipid peroxidation
inhibition. Nutrition 1999;15:790-1.
Lesser S, Cormak R, Wolffram S. Bioavailability of quercetin in pigs is
influenced by the dietary fat content. J Nutr 2004;134:1508-11.
van Dijk C, Driessen AJ, Recourt K. The uncoupling efficiency and affinity
of flavonoids for vesicles. Biochem Pharmacol 2000;60:1593-600.
Kidd PM. Phosphatidylcholine: A Superior Protectant against Liver
Damage. Altern Med Rev 1996;1:258-74.
Taira MC, Chiaramoni NS, Pecuch KM, Alonso-Romanowski S. Stability
of Liposomal Formulations in Physiological Conditions for Oral Drug
Delivery. Drug Deliv 2004;11:123-8.
Calabrò ML, Tommasini S, Donato P, Raneri D, Stancanelli R, Ficarra P,
et al. Effects of α- and β-cyclodextrin complexation on the physico-
chemical properties and antioxidant activity of some 3-hydroxyflavones.
J Pharm Biomed Anal 2004;35:365-77.
Calabrò ML, Tommasini S, Donato P, Stancanelli R, Raneri D, Catania S,
et al. The rutin/β-cyclodextrin interactions in fully aqueous solution:
Spectroscopic studies and biological assays. J Pharm Biomed Anal
;36:1019-27.
Tedeschi A, D’Errico G, Lauro M, Sansone F, Marino S, D’Ursi A, et al.
Effect of flavonoids on the Ab(25-35)-phospholipid bilayers interaction.
Eu J Med Chem 2010;45:3998-4003.
Movileanu L, Neagoe I, Flonta ML. Interaction of the antioxidant flavonoid quercetin with planar lipid bilayers. Int J Pharm 2000;205:135- 6.4
Priprem A, Watanatorn J, Sutthiparinyanont S, Phachonpai W,
Muchimapura S. Anxiety and Cognitive effects of Quercetin liposomes
in rats. Nanomedicine 2008;4:70-8.
Liu X, Yang Q, Kamo N, Miyake J. Effect of liposome type and membrane
fluidity on drug–membrane partitioning analyzed by immobilized
liposome chromatography. J Chrom 2001;913:123-31.
Lichtenberg D, Zilberman Y, Greenzaid P, Zamir S. Structural and kinetic
studies on the solubilization of lecithin by sodium deoxycholate.
Biochemistry 1979;18:3517-25.
Maestrelli F, Gonzalez-Rodriguez ML, Rabasco AM, Mura P. Preparation
and characterisation of liposomes encapsulating ketoprofen–
cyclodextrin complexes for transdermal drug delivery. Int J Pharm
;298:55-67.
Fatouros DG, Hatzidimitriou K, Antimisiaris SG. Liposomes
encapsulating prednisolone and prednisolone-cyclodextrin complexes:
Comparison of membrane integrity and drug release. Eur J Pharm Sci
;13:287-96.
Skalko, N, Brandl M, Becirevic-Lacan M, Filipovic-Greic J,
Jalsenjak I. Liposome with nifedipine and nifedipine-cyclodextrin
complex: Calorimetrical and plasma stability comparison. Eur J Pharm
Sci 1996;4:359-66.
Bouldemarat L, Bochot A, Lesieur S, Fattal E. The mechanism of
destabilization of lipid membranes by methylated β-cyclodextrins. In:
Proceedings of the 12th International Cyclodextrin Symposium 2004.
p. 707-10.
Gasbarri C, Guernelli S, Boncompagni S, Angelini G, Siani G, De Maria P,
et al. Fine-tuning of POPC liposomal leakage by the use of β-cyclodextrin
and several hydrophobic guests. J Liposome Res 2010;20:202-10.
Gutteridge JM. Lipid Peroxidation and Antioxidants as Biomarkers of
Tissue Damage. Clin Chem 1995;41:1819-28.
Terao J, Piskula M, Yao Q. Protective effect of epicatechin, epicatechin
gallate, and quercetin on lipid peroxidation in phospholipid bilayers.
Arch Biochem Biophys 1994;308:278-84.
Ioku K, Tsushida T, Takei Y, Nakatani N, Terao J. Antioxidative activity of
quercetin and quercetin monoglucosides in solution and phospholipid
bilayers. Biochim Biophys Acta 1995;1234:99-104.
Malaekeh-Nikouei B, Davies N. Double loading of cyclosporine A in
liposomes using cyclodextrin complexes. PDA J Pharm Sci Technol.
;63:139-48.
Kumar R, Gupta RB, Betageri GV. Formulation, Characterization, and
In vitro Release of Glyburide from Proliposomal Beads. Drug Delivery
;8:25-7.
Brocks DR, Betageri GV. Enhanced oral absorption of halofantrine
enantiomers after encapsulation in a proliposomal formulation. J Pharm
Pharmacol 2002;54:1049-53.
Betageri GV. Enteric-coated proliposomal formulations for poorly water soluble drugs. USPTO- US006759058B1. 2004.