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Pharmaceutical Nanotechnology

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ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

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Research Article

Designing and Formulation Optimization of Hyaluronic Acid Conjugated PLGA Nanoparticles of Tamoxifen for Tumor Targeting

Author(s): Suresh K. Paswan, Tulsi R. Saini*, Sarwar Jahan and Narayanan Ganesh

Volume 9, Issue 3, 2021

Published on: 10 March, 2021

Page: [217 - 235] Pages: 19

DOI: 10.2174/2211738509666210310155807

Price: $65

Abstract

Background: Tamoxifen is widely used for the treatment of estrogen receptor-positive breast cancer. However, it is associated with severe side effects of cancerous proliferation on the uterus endometrium. The tumor-targeting formulation strategies can effectively overcome drug side effects of tamoxifen and provide safer drug treatment.

Objective: This study aimed to design tumor-targeted PLGA nanoparticles of tamoxifen by attaching hyaluronic acid (HA) as a ligand to actively target the CD44 receptors present at breast cancer cells surface.

Methods: PLGA-PEG-HA conjugate was synthesized in the laboratory, and its tamoxifen-loaded nanoparticles were fabricated and characterized by FTIR, NMR, DSC, and XRD analysis. Formulation optimization was done by Box-Behnken design using Design-Expert software. The formulations were evaluated for in vitro drug release and cytotoxic effect on MCF-7 cell lines.

Results: The particle size, PDI, and drug encapsulation efficiency of optimized nanoparticles were 294.8, 0.626, and 65.16%, respectively. Optimized formulation showed 9.56% burst release and sustained drug release for 8h. The drug release was affected by non-Fickian diffusion process and supplemented further by the erosion of polymeric matrix which followed the Korsmeyer-Peppas model. MTT cell line assay showed 47.48% cell mortality when treated with tamoxifen-loaded PLGA- PEG-HA nanoparticles.

Conclusion: Hyaluronic acid conjugated PLGA-PEG nanoparticles of tamoxifen were designed for active targeting to cancerous breast cells. The results of the MTT assay showed that tamoxifen nanoparticles formulation was more cytotoxic than tamoxifen drug alone, which is attributed to their preferential uptake by cell lines by the affinity of CD44 receptors of cell lines to HA ligand present in nanoparticles.

Keywords: PLGA-PEG-HA, tamoxifen nanoparticles, tamoxifen, hyaluronic acid attached tumor-targeted nanoparticles, ligand attached PLGA-PEG-HA nanoparticles, targeted delivery of tamoxifen, tamoxifen loaded tumor-targeted nanoparticle formulation development.

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[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
MacGregor JI, Jordan VC. Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 1998; 50(2): 151-96.
[PMID: 9647865]
[3]
Jordan VC. Tamoxifen: toxicities and drug resistance during the treatment and prevention of breast cancer. Annu Rev Pharmacol Toxicol 1995; 35: 195-211.
[http://dx.doi.org/10.1146/annurev.pa.35.040195.001211] [PMID: 7598491]
[4]
Yildirim Y, Inal MM, Sanci M, et al. Development of uterine sarcoma after tamoxifen treatment for breast cancer: report of four cases. Int J Gynecol Cancer 2005; 15(6): 1239-42.
[http://dx.doi.org/10.1111/j.1525-1438.2005.00170.x] [PMID: 16343223]
[5]
Mourits MJ, De Vries EG, Willemse PH, Ten Hoor KA, Hollema H, Van der Zee AG. Tamoxifen treatment and gynecologic side effects: a review. Obstet Gynecol 2001; 97(5 Pt 2): 855-66.
[http://dx.doi.org/10.1097/00006250-200105000-00055] [PMID: 11336777]
[6]
Khan I, Saeed K, Khan I. Nanoparticles: properties, applications and toxicities. Arab J Chem 2019; 12(7): 908-31.
[http://dx.doi.org/10.1016/j.arabjc.2017.05.011]
[7]
Gupta RB, Kompella UB. Fundamentals of drug nanoparticles. Drugs and the pharmaceutical sciences: Nanoparticle technology for drug delivery 159. New York: Taylor & Francis Group 2006; pp. 6-9.
[http://dx.doi.org/10.1201/9780849374555]
[8]
Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM, McCullough J. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine (Lond) 2013; 9(1): 1-14.
[http://dx.doi.org/10.1016/j.nano.2012.05.013] [PMID: 22684017]
[9]
Khatoon UT, Rao GVSN, Mohan MK, Ramanaviciene A, Ramanavicius A. Comparative study of antifungal activity of silver and gold nanoparticles synthesized by facile chemical approach. J Environ Chem Eng 2018; 6(5): 5837-44.
[http://dx.doi.org/10.1016/j.jece.2018.08.009]
[10]
Kreuter J. Nanoparticle-based drug delivery systems. J Control Release 1991; 16(1): 169-76.
[http://dx.doi.org/10.1016/0168-3659(91)90040-K]
[11]
Couvreur P, Vauthier C. Nanotechnology: intelligent design to treat complex disease. Pharm Res 2006; 23(7): 1417-50.
[http://dx.doi.org/10.1007/s11095-006-0284-8] [PMID: 16779701]
[12]
Huang J, Zhang H, Yu Y, et al. Biodegradable self-assembled nanoparticles of poly (D,L-lactide-co-glycolide)/hyaluronic acid block copolymers for target delivery of docetaxel to breast cancer. Biomaterials 2014; 35(1): 550-66.
[http://dx.doi.org/10.1016/j.biomaterials.2013.09.089] [PMID: 24135268]
[13]
Zhang Z, Feng SS. The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. Biomaterials 2006; 27(21): 4025-33.
[http://dx.doi.org/10.1016/j.biomaterials.2006.03.006] [PMID: 16564085]
[14]
Fasehee H, Dinarvand R, Ghavamzadeh A, et al. Delivery of disulfiram into breast cancer cells using folate-receptor-targeted PLGA-PEG nanoparticles: in vitro and in vivoinvestigations. J Nanobiotechnology 2016; 14: 32.
[http://dx.doi.org/10.1186/s12951-016-0183-z] [PMID: 27102110]
[15]
Yadav AK, Mishra P, Mishra AK, Mishra P, Jain S, Agrawal GP. Development and characterization of hyaluronic acid-anchored PLGA nanoparticulate carriers of doxorubicin. Nanomedicine (Lond) 2007; 3(4): 246-57.
[http://dx.doi.org/10.1016/j.nano.2007.09.004] [PMID: 18068091]
[16]
Yadav AK, Agarwal A, Rai G, et al. Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil. Drug Deliv 2010; 17(8): 561-72.
[http://dx.doi.org/10.3109/10717544.2010.500635] [PMID: 20738221]
[17]
Yadav AK, Mishra P, Jain S, Mishra P, Mishra AK, Agrawal GP. Preparation and characterization of HA-PEG-PCL intelligent core-corona nanoparticles for delivery of doxorubicin. J Drug Target 2008; 16(6): 464-78.
[http://dx.doi.org/10.1080/10611860802095494] [PMID: 18604659]
[18]
Zalipsky S. Chemistry of polyethylene glycol conjugates with biologically active molecules. Adv Drug Deliv Rev 1995; 16(2-3): 157-82.
[http://dx.doi.org/10.1016/0169-409X(95)00023-Z]
[19]
El-Gogary RI, Rubio N, Wang JT, et al. Polyethylene glycol conjugated polymeric nanocapsules for targeted delivery of quercetin to folate-expressing cancer cells in vitro and in vivo. ACS Nano 2014; 8(2): 1384-401.
[http://dx.doi.org/10.1021/nn405155b] [PMID: 24397686]
[20]
Vangara KK, Liu JL, Palakurthi S. Hyaluronic acid-decorated PLGA-PEG nanoparticles for targeted delivery of SN-38 to ovarian cancer. Anticancer Res 2013; 33(6): 2425-34.
[PMID: 23749891]
[21]
Paswan SK, Saini TR. Purification of drug loaded plga nanoparticles prepared by emulsification solvent evaporation using stirred cell ultrafiltration technique. Pharm Res 2017; 34(12): 2779-86.
[http://dx.doi.org/10.1007/s11095-017-2257-5] [PMID: 28924739]
[22]
Ferreira SL, Bruns RE, Ferreira HS, et al. Box-Behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta 2007; 597(2): 179-86.
[http://dx.doi.org/10.1016/j.aca.2007.07.011] [PMID: 17683728]
[23]
Ravikumara NR, Bharadwaj M, Madhusudhan B. Tamoxifen citrate-loaded poly(d,l) lactic acid nanoparticles: evaluation for their anticancer activity in vitro and in vivo. J Biomater Appl 2016; 31(5): 755-72.
[http://dx.doi.org/10.1177/0885328216670561] [PMID: 27664187]
[24]
Magenheim B, Levy MY, Benita S. A new in vitro technique for the evaluation of drug release profile from colloidal carriers - ultrafiltration technique at low pressure. Int J Pharm 1993; 94(1-3): 115-23.
[http://dx.doi.org/10.1016/0378-5173(93)90015-8]
[25]
Paswan SK, Saini TR. Comparative evaluation of different in vivo drug release methods employed for testing of nanoparticles drug release studies. 2020.
[26]
Yan W, Chen Y, Yao Y, Zhang H, Wang T. Increased invasion and tumorigenicity capacity of CD44+/CD24- breast cancer MCF7 cells in vitro and in nude mice. Cancer Cell Int 2013; 13(1): 62.
[http://dx.doi.org/10.1186/1475-2867-13-62] [PMID: 23799994]
[27]
Sun H, Jia J, Wang X, et al. CD44+/CD24- breast cancer cells isolated from MCF-7 cultures exhibit enhanced angiogenic properties. Clin Transl Oncol 2013; 15(1): 46-54.
[http://dx.doi.org/10.1007/s12094-012-0891-2] [PMID: 22855175]
[28]
Scudiero DA, Shoemaker RH, Paull KD, et al. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 1988; 48(17): 4827-33.
[PMID: 3409223]
[29]
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): 581-93.
[http://dx.doi.org/10.1046/j.1471-4159.1997.69020581.x] [PMID: 9231715]
[30]
Silverstein RM, Webster FX. Spectrometric identification of organic compounds. 6th ed. United States: John Wiley & Sons 2006.
[31]
Shkodra-Pula B, Grune C, Traeger A, et al. Effect of surfactant on the size and stability of PLGA nanoparticles encapsulating a protein kinase C inhibitor. Int J Pharm 2019; 566: 756-64.
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.072] [PMID: 31175987]
[32]
Sahoo SK, Panyam J, Prabha S, Labhasetwar V. Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J Control Release 2002; 82(1): 105-14.
[http://dx.doi.org/10.1016/S0168-3659(02)00127-X] [PMID: 12106981]
[33]
Santos HM, Lodeiro C, Capelo-Martínez JL. The power of ultrasound Ultrasound in chemistry: Analytical applications. United States: Wiley Online Library 2009; pp. 1-16.
[34]
Choi SJ, McClements DJ. Nanoemulsions as delivery systems for lipophilic nutraceuticals: strategies for improving their formulation, stability, functionality and bioavailability. Food Sci Biotechnol 2020; 29(2): 149-68.
[http://dx.doi.org/10.1007/s10068-019-00731-4] [PMID: 32064124]
[35]
Danaei M, Dehghankhold M, Ataei S, et al. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics 2018; 10(2): E57.
[http://dx.doi.org/10.3390/pharmaceutics10020057] [PMID: 29783687]
[36]
Busatto C, Pesoa J, Helbling I, Luna J, Estenoz D. Effect of particle size, polydispersity and polymer degradation on progesterone release from PLGA microparticles: Experimental and mathematical modeling. Int J Pharm 2018; 536(1): 360-9.
[http://dx.doi.org/10.1016/j.ijpharm.2017.12.006] [PMID: 29217474]
[37]
Xu Q, Hashimoto M, Dang TT, et al. Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow-focusing device for controlled drug delivery. Small 2009; 5(13): 1575-81.
[http://dx.doi.org/10.1002/smll.200801855] [PMID: 19296563]
[38]
Samimi S, Maghsoudnia N, Eftekhari RB, Dorkoosh F. Lipid-based nanoparticles for drug delivery systems.characterization and biology of nanomaterials for drug delivery.Characterization and Biology of Nanomaterials for Drug Delivery. Netherlands: Elsevier 2019; pp. 47-76.
[http://dx.doi.org/10.1016/B978-0-12-814031-4.00003-9]
[39]
Kathe N, Henriksen B, Chauhan H. Physicochemical characterization techniques for solid lipid nanoparticles: principles and limitations. Drug Dev Ind Pharm 2014; 40(12): 1565-75.
[http://dx.doi.org/10.3109/03639045.2014.909840] [PMID: 24766553]
[40]
Saneja A, Nayak D, Srinivas M, et al. Development and mechanistic insight into enhanced cytotoxic potential of hyaluronic acid conjugated nanoparticles in CD44 overexpressing cancer cells. Eur J Pharm Sci 2017; 97: 79-91.
[http://dx.doi.org/10.1016/j.ejps.2016.10.028] [PMID: 27989859]
[41]
Pradhan R, Ramasamy T, Choi JY, et al. Hyaluronic acid-decorated poly(lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin. Carbohydr Polym 2015; 123: 313-23.
[http://dx.doi.org/10.1016/j.carbpol.2015.01.064] [PMID: 25843864]
[42]
Maji R, Dey NS, Satapathy BS, Mukherjee B, Mondal S. Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy. Int J Nanomedicine 2014; 9: 3107-18.
[PMID: 25028549]
[43]
Hu FX, Neoh KG, Kang ET. Synthesis and in vitro anti-cancer evaluation of tamoxifen-loaded magnetite/PLLA composite nanoparticles. Biomaterials 2006; 27(33): 5725-33.
[http://dx.doi.org/10.1016/j.biomaterials.2006.07.014] [PMID: 16890989]
[44]
Saharan P, Bahmani K, Saharan SP. Preparation, optimization and in vitro evaluation of glipizide nanoparticles integrated with Eudragit RS-100. Pharm Nanotechnol 2019; 7(1): 72-85.
[http://dx.doi.org/10.2174/2211738507666190319124513] [PMID: 30892168]
[45]
Ortiz MC, Herrero A, Sanllorente S, Reguera C. Methodology of multicriteria optimization in chemical analysis some applications in stripping voltammetry. Talanta 2005; 65(1): 246-54.
[http://dx.doi.org/10.1016/S0039-9140(04)00356-X] [PMID: 18969791]
[46]
Rawlings JO, Pantula SG, Dickey DA. Applied regression analysis: a research tool. New York, USA: Springer-Verlag 1998.
[http://dx.doi.org/10.1007/b98890]
[47]
Bolton S, Bon C. Pharmaceutical Statistics: Practical and Clinical Applications. 5th ed. New York, USA: Informa Healthcare USA, Inc. 2010.
[48]
Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010; 67(3): 217-23.
[PMID: 20524422]
[49]
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983; 15(1): 25-35.
[http://dx.doi.org/10.1016/0378-5173(83)90064-9]
[50]
Ritger PL, Peppas NA. A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Control Release 1987; 5(1): 23-36.
[http://dx.doi.org/10.1016/0168-3659(87)90034-4]
[51]
Pradhan R, Poudel BK, Choi JY, et al. Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles. Arch Pharm Res 2015; 38(5): 734-41.
[http://dx.doi.org/10.1007/s12272-014-0404-7] [PMID: 24824337]
[52]
Clas SD, Dalton CR, Hancock BC. Differential scanning calorimetry: applications in drug development. Pharm Sci Technol Today 1999; 2(8): 311-20.
[http://dx.doi.org/10.1016/S1461-5347(99)00181-9] [PMID: 10441275]
[53]
Fathy M, Hassan MA, Mohamed FA. Differential scanning calorimetry to investigate the compatibility of ciprofloxacin hydrochloride with excipients. Pharmazie 2002; 57(12): 825-8.
[PMID: 12561245]
[54]
de Lima GR, Facina G, Shida JY, et al. Effects of low dose tamoxifen on normal breast tissue from premenopausal women. Eur J Cancer 2003; 39(7): 891-8.
[http://dx.doi.org/10.1016/S0959-8049(02)00530-0] [PMID: 12706357]
[55]
Rao NV, Yoon HY, Han HS, et al. Recent developments in hyaluronic acid-based nanomedicine for targeted cancer treatment. Expert Opin Drug Deliv 2016; 13(2): 239-52.
[http://dx.doi.org/10.1517/17425247.2016.1112374] [PMID: 26653872]

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