β-lactoglobulin-irinotecan inclusion complex as a new targeted nanocarrier for colorectal cancer cells

Nooshin Bijari , Sirous Ghobadi, Katayoun Derakhshandeh

Abstract


Beta-lactoglobulin (β-LG) is a lipocalin family member whose general function appears to be solubilizing and transport of hydrophobic molecules. Some properties such as avalability, ease of purification,  and peculiar resistance to acidic environments can make β-LG as a carrier for hydrophobic and acid labile drugs for oral administration. In this protein vehicle, drug could be protected in acidic environment of stomach and then released within the basic small intestine. In this study, the potential of β-LG   as a nanocarrier for oral delivery of a potent agent in colorectal cancer treatment, irinotecan, was evaluated. The nanoparticle was prepared by the physical inclusion complex method. Size, drug loading, encapsulation efficiency, and in vitro drug release at various pH values were investigated. The optimum formulation showed a narrow size distribution with an average diameter of 139.86 ± 13.75 nm and drug loading about 84.33 ± 5.03%. Based on the results obtained from docking simulation of irinotecan-complex,   there are two distinct binding sites in this nanocarrier. Cytotoxicity of this nanocarrier on the HT-29 cancer cell line and AGS was measured by MTT assay. The cytotoxicity experiment showed that the drug-loaded nanocarrier was more effective than free drug. The higher release percent of drug from the β-LG complex  at pH 7.4 compared to pH 1.2 indicated that the proposed nanocarrier could be introduced as a suitable nanovehicle for labile drugs in acidic medium targeted for colorectal segment.


Keywords


Beta-lactoglobulin; Colorectal cancer; Irinotecan; Nano drug delivery system.

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Mazzaferro S, Bouchemal K, Ponchel G. Oral delivery of anticancer drugs III: formulation using drug delivery systems. Drug Discov Today. 2013;18(1-2):99-104.

Caillard R, Boutin Y, Subirade M. Characterization of succinylated β-lactoglobulin and its application as the excipient in novel delayed release tablets. Int Dairy J. 2011;21(1):27-33.

Kepple rJK, Sonnichsen FD, Lorenzen PC, Schwarz K. Differences in heat stability and ligand binding among β-lactoglobulin genetic variants A, B and C using (1)H NMR and fluorescence quenching. Biochim Biophys Acta. 2014;1844(6):1083-1093.

Halder UC, Chakraborty J, Das N, Bose S. Tryptophan dynamics in the exploration of micro-conformational changes of refolded β-lactoglobulin after thermal exposure: a steady state and time-resolved fluorescence approach. J Photochem Photobiol B. 2012;109:50-57.

Caillard R, Remondetto GE, Mateescu MA, Subirade M. Characterization of amino cross-linked soy protein hydrogels. J Food Sci. 2008;73(5): C283-C291.

Caillard R, Petit A, Subirade M. Design and evaluation of succinylated soy protein tablets as delayed drug delivery tablets. Int J Biol Macromol. 2009;45(4):414-420.

KonumaT, Sakurai K, GotoY. Promiscuous binding of ligands by beta-lactoglobulin involves hydrophobic interactions and plasticity. J Mol Biol. 2007;368(1):209-218.

ChakrabortyJ, DasN, HalderUC. Unfolding diminishes fluorescence resonance energy transfer (FRET) of lysine modified β-lactoglobulin: Relevance towards anti-HIV binding. J Photochem Photobiol B. 2011;102(1):1-10.

Le Maux S, Bouhallab S, Giblin L, Brodkorb A, Croguennec T. Bovine β-lactoglobulin/fatty acid complexes: binding, structural, and biological properties. Dairy Sci Technol. 2014;94(5):409-426.

QinB Y, Bewley MC, Creamer LK, Baker HM, Baker EN, Jameson GB. Structural basis of the Tanford transition of bovine beta-lactoglobulin. Biochemistry. 1998;37(40):14014-14023.

Rivory LP. New drugs for colorectal cancer-mechanisms of action. Exp Clin Pharmacol. 2005;25(5):108-110.

Potmesil M. Camptothecins: from bench research to hospital wards. Cancer Res. 1994;54(6): 1431-1439.

Kaneda N, Nagata H, Furuta T, Yokokura T. Metabolism and pharmacokinetics of the camptothecin analogue CPT-11 in the mouse. Cancer Res. 1990;50:1715-1720.

Derakhshandeh K, Erfan M, Dadashzade S. Encapsulation of 9-nitrocamptothecin, a novel anticancer drug, in biodegradable nanoparticles: factorial design, characterization and release kinetics. Eur J Pharm Biopharm. 2007;66(1):34-41.

Fassberg J, Stella VJ. A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues. J Pharm Sci. 1992;81(7):676-684.

Diasio RB. Current status of oral chemotherapy for colorectal cancer. Oncology (Williston Park). 2001;15(3 Suppl 5):16-20.

Sharma S, Saltz LB. Oral chemotherapeutic agents for colorectal cancer. Oncologist. 2000;5(2):99-107.

Houghton PJ, Stewart CF, Zamboni WC, Thompson J, Luo X, Danks MK, et al. Schedule-dependent efficacy of camptothecins in models of human cancer. Ann N Y Acad Sci. 1996;803:188-201.

Drengler RL, Kuhn JG, Schaaf LJ, Rodriguez GI, Villalona-Calero MA, Hammond LA, et al. Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors. J Clin Oncol. 1999;17(2):685-696.

Ghalandari B, Divsalar A, Saboury AA, Parivar K. The new insight into oral drug delivery system based on metal drugs in colon cancer therapy through β-lactoglobulin/oxali-palladium nanocapsules. J Photochem Photobiol B. 2014;140:255-265.

Kashanian S, Hemati Azandariyani A, Derakhshandeh K. New surface-modified solid lipid nanoparticles using N-glutaryl phosphatidyl ethanolamine as the outer shell. Int J Nanomedicine. 2011;6:2393-2401.

McConnell EL, Fadda HM, Basit AW. Gut instincts: explorations in intestinal physiology and drug delivery. Int J Pharm. 2008;364(2):213-226.

EvansDF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut. 1998;29(8):1035-1041.

Varelas CG, Dixon DG, Steiner CA. Zero-order release from biphasic polymer hydrogels. J Control Release. 1995;34(3):185-192.

Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-133.

Higuchi T. Mechanism of sustained-action medication, theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145-1149.

Hixson AW, Crowell JH. Dependence of reaction velocity upon surface and agitation. Ind Eng Chem Res. 1931;23(8):923-931.

Prodduturi S, Urman KL, Otaigbe JU, Repka MA. Stabilization of hot-melt extrusion formulations containing solid solutions using polymer blends. AAPS PharmSciTech. 2007;8(2):E152-E161.

Barzegar-Jalali M, Adibkia K, Valizadeh H, Shadbad MR, Nokhodchi A, Omidi Y, et al. Kinetic analysis of drug release from nanoparticles. J Pharm Pharm Sci. 2008;11(1):167-177.

Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, et al. Automated docking using Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 1998;19:1639-1662.

Froimowitz M. HyperChem: a software package for computational chemistry and molecular modeling. Biotechniques 1993;14(6):1010-1013.

Liu Y, Peterson DA, Kimura H, Schubert D. Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem. 1997;69(2):581-593.

Adams JJ, Anderson BF, Norris GE, Creamer LK, Jameson GB. Structure of bovine beta-lactoglobulin (variant A) at very low ionic strength. J Srtuct Biol. 2006;154(3):246-254.

Naik PN, Nandibewoor ST, Chimatadar SA. Non-covalent binding analysis of sulfamethoxazole to human serum albumin: Fluorescence spectroscopy, UV-vis, FT-IR, voltammetric and molecular modeling. J Pharm Anal. 2015; 5(3): 143-152.

Gao W, Li N, Chen Y, Xu Y, Lin Y, Yin Y, et al. Study of interaction between syringin and human serum albumin by multi-spectroscopic method and atomic force microscopy. J Mol Struct. 2010;983(1-3):133-140.

Sawyer L, Brownlow S, Polikarpov I, Wu SY. β-Lactoglobulin: structural studies, biological clues. Int Dairy J. 1998;8(2):65-72.

Shukla S, Jadaun A, Arora V, Sinha RK, Biyani N, Jain V. In vitro toxicity assessment of chitosan oligosaccharide coated iron oxide nanoparticles. Toxicol Rep.2014;2:27-39.

Chanasattru W, Jones OG, Decker EA, McClements DJ. Impact of cosolvents on formation and properties of biopolymer nanoparticles formed by heat treatment of β-lactoglobulin-Pectin complexes. Food Hydrocoll. 2009;23(8):2450-2457.

Bijari N, Ghobadi S, Derakhshandeh K. Irinotecan binds to the internal cavity of beta-lactoglobulin: A multi-spectroscopic and computational investigation. J Pharm Biomed Anal. 2017;139:109-115

Bijari N, Moradi S, Ghobadi S, Shahlaei M. Elucidating the interaction of letrozole with human serum albumin by combination of spectroscopic and molecular modeling techniques. Res Pharm Sci. 2018;13(4):304-315.

Wallace AC, Laskowski RA, Thornton JM. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 1995;8(2):127-134.


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