Encapsulation of Doxorubicin and Chrysin on magnetic PCL-PEG-PCL nanoparticles: Optimization of parameters and drug delivery evaluation

Document Type : Reasearch Paper

Authors

• Sahar Jahangiri ¹
• Leila Amirkhani ²
• Abolfazl Akbarzadeh ^{3, 4}
• Reza Hajimohammadi ²

¹ Ph.D student of Department of Chemical Engineering, Ahar Branch, Islamic Azad University, Ahar, Iran.

² Department of Chemical Engineering, Ahar Branch, Islamic Azad University, Ahar, Iran.

³ Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

⁴ Department of Medical Nanotechnologies, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

10.22034/ijnd.2021.682870

Abstract

Iron oxide nanoparticles are smart materials that have been commonly used in medicine for diagnostic imaging, drug delivery, and therapeutic applications. In this study, Iron oxide nanoparticles and Doxorubicin (DOX)- Chrysin (Chr), were absorbed into triblock copolymer (PCL-PEG-PCL) for narrow behavior. PCL-PEG triblock copolymers were synthesized by ring-opening polymerization of ε-caprolactone (ε-CL) with polyethylene glycol (EG) as an initiator. The bulk properties and chemical structure of these copolymers were characterized using Fourier transform infrared spectroscopy and ¹H-NMR. In adding together, the consequential particles were characterized by scanning electron microscopy, X-ray powder diffraction, vibrating sample magnetometry, and zeta potential measurement. Response surface methodology (RSM) was employed to study the effects of the three most important parameters on encapsulation efficiency, namely DOX and Chr weight (2-18 mg), ε -CL weight (0.6-3.8 g), and sonication time (15-75s). The optimum encapsulation conditions were: 11.2 mg for DOX and Chr weight, 3.75 g for ε -CL, and 48.15 s for sonication time. The highest encapsulation efficiency in these conditions predicted by the equation is 95.68% and the release profile was controlled. There is potential for the application of Fe₃O₄- PCL-PEG₄₀₀₀ magnetic nanoparticles for biomedical purposes.

Keywords

• Chrysin
• Doxorubicin
• Iron Oxide Nanoparticles
• PCL-PEG
• Triblock Copolymer

20.1001.1.20088868.2021.12.4.7.8

---

References

[1] Prabhakar U., Maeda H., Jain R. K., Sevick-Muraca E. M., Zamboni W., Farokhzad O. C., Barry S. T., Gabizon A., Grodzinski P., Blakey D. C., (2013), Challenges and key considerations of the enhanced permeability and retentioneffect for nanomedicine drug delivery in oncology. Cancer. Res. 73: 2412-2417.

[2] Hazhir N., Chekin F., Raoof J. B., Fathi S. H., (2021), Anticancer activity of Doxorubicin conjugated to polymer/carbon based-nanohybrid against MCF-7 breast and HT-29 colon cancer cells. Int. J. Nano Dimens. 12: 11-19.

[3] Tayebee R., Fattahi Abdizadeh M., Mohammadpour Amini M., Mollania N., Jalilli Z., Akbarzadeh H., (2017), Fe₃O₄@SiO₂-NH₂ as an efficient nanomagnetic carrier for controlled loading and release of acyclovir. Int. J. Nano Dimens. 8: 365-372.

[4] Nikfar Z., Shariatinia Z., (2020), Tripeptide arginyl-glycyl-aspartic acid (RGD) for delivery of Cyclophosphamide anticancer drug: A computational approach. Int. J. Nano Dimens. 11: 312-336.

[5] Shabestari-Khiabani S., Farshbaf M., Akbarzadeh A., Davaran S., (2017), Magnetic nanoparticles: Preparation methods, applications in cancer diagnosis and cancer therapy. Artif. Cells Nanomed. Biotechnol. 45: 6-17.

[6] Ye F., Barrefelt A., Asem H., Abedi-Valugerdi M., El-Serafi I., Saghafian M., Abu-Salah K., Alrokayan S., Muhammed M., Hassan M., (2014), Biodegradable polymeric vesicles containing magnetic nanoparticles, quantum dots and anticancer drugs for drug delivery and imaging. Biomaterials. 35: 3885- 3894.

[7] Asadi N., Annabi N., Mostafavi E., Anzabi M., Khalilov R., Saghfi S., Masoud Mehrizadeh M.,  Akbarzadeh A., (2018), Synthesis, characterization and in vitro evaluation of magnetic nanoparticles modified with PCL–PEG–PCL for controlled delivery of 5FU. Artif. Cells, Nanomed., Biotechnol. 46: 938-945.

[8] Gorjikhah F., Azizi Jalalian F., Salehi R., Panahi Y., Hasanzadeh A., Alizadeh E., Akbarzadeh A., Davaran S., (2016), Preparation and characterization of PLGA-β-CD polymeric nanoparticles containing methotrexate and evaluation of their effects on T47D cell line. Artif. Cells, Nanomed., Biotechnol. 45: 432-440.

[9] Mou X., Ali Z., Li S., He N., (2015), Applications of magnetic nanoparticles in targeted drug delivery system. J. Nanosci. Nanotechnol. 15: 54-62.

[10] Ulbrich K., Holá K., Šubr V., Bakandritsos A., Tuček R., Zbořil J., (2016), Targeted drug delivery with polymers and magnetic nanoparticles: Covalent and noncovalent approaches, release control, and clinical studies. Chem. Rev. 116: 5338-5431.

[11] Farshbaf. M., Salehi. R., Annabi. N., Khalilov. R., Akbarzadeh. A., Davaran. S., (2017), pH- and thermo-sensitive MTX-loaded magnetic nanocomposites: Synthesis, characterization, and in vitro studies on A549 lung cancer cell and MR imaging. Drug Dev. Ind. Pharm. 44: 452-462.

[12] Reis C. P., Neufeld R. J., Ribeiro A. J., Veiga F., (2006), Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomed. Nanotechnol. Biol. Med. 2: 8-21.

[13] Veiseh O., Gunn J. W., Zhang M., (2010), Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv. Drug Delivery Rev. 62: 284-304.

[14] Aberoumandi S. M., Mohammadhosseini M., Abasi. E., Saghati. S., Nikzamir. N., Akbarzadeh. A., Panahi. Y., Davaran. S., (2016),An update on applications of nanostructured drug delivery systems in cancer therapy: A review. Artif. Cells, Nanomed., Biotechnol. 45: 1058-1068.

[15] Ahmadkhani L., Akbarzadeh A., Abbasian M., (2017), Development and characterization dual responsive magnetic nanocomposites for targeted drug delivery systems. Artif. Cells, Nanomed. Biotechnol. 46: 1052-1063.

[16] Ramos S., (2008), Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways. Mol.Nutr. Food Res. 52: 507-526.

[17] Jaganathan S. K., Mandal M., (2009), Antiproliferative effects of honey and of its polyphenols: A review. BioMed Res. Int. 2009: 1-13.

[18] Kwon Y., Kim H., Park S., Jung S., (2010), Enhancement of solubility and antioxidant activity of some flavonoids based on the inclusion complexation with sulfobutylether β-cyclodextrin. Bull. Korean Chem. Soc. 31: 3035-3037.

[19] Walle U. K., Galijatovic A., Walle T., (1999), Transport of the flavonoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2. Biochem. Pharmacol. 58: 431-438.

[20] Munin A., Edwards-Lévy F., (2011), Encapsulation of natural polyphenolic compounds; A review. Pharmaceutics. 3: 793-829.

[21] Jahangiri. S., Akbarzadeh. A., (2015), Preparation and in vitro evaluation of Methotrexate-loaded magnetic nanoparticles modified with biocompatible copolymers. Artif. Cells, Nanomed., Biotechnol. 44: 1733-1740.

[22] Mostafavi E., Babaei A., Ataie A., (2015), Synthesis of nano-structured La_0.6 Sr_0.4 Co_0.2 Fe₀.₈O₃ perovskite by co-precipitation method. J. Ultrafine Grained Nanostruct. Mater. 48: 45-52.

[23] Yang J., Park S. B., Yoon H. G., Huh Y. M., Haam S., (2006), Preparation of poly caprolactone nanoparticles containing magnetite for magnetic drug carrier. Int. J. Pharm. 324: 185-190.

[24] Diaz Duarte-Rodriguez M., Cortez-Lemus N., Licea-Claverie A., Licea-Rodriguez J., Méndez E., (2019), Dual responsive polymersomes for gold nanorod and Doxorubicin encapsulation: Nanomaterials with potential use as smart drug delivery systems. Polymers. 11: 939-945.

[25] Firouzi-Amandi A., Dadashpour M., Nouri M., Zarghami N., Serati-Nouri H., Jafari-Gharabaghlou D., Hazhir Karzar B., Hassan Mellatyar H., Aghebati-Maleki L., Zohreh Babaloo Z., Pilehvar-Soltanahmadi Y., (2018), Chrysin-nanoencapsulated PLGA-PEG for macrophage repolarization: Possible application in tissue regeneration. Biomed. Pharmacother. 105: 773–780.

[26] Liu J., Qiu Z., Wang Sh., Zhou L., Zhang Sh., (2010), A modified double-emulsion method for the preparation of daunorubicin-loaded polymeric nanoparticle with enhanced in vitro anti-tumor activity. Biomed. Mater.5: 065002.

[27] Motaali S., Pashaeiasl M., Akbarzadeh A., Davaran S., (2017), Synthesis and characterization of smart N-isopropylacrylamide-based magnetic nanocomposites containing doxorubicin anti-cancer drug. Artif. Cells Nanomed. Biotechnol. 45: 560-567.

[28] Valizadeh A., Bakhtiary M., Akbarzadeh A., Salehi R., Mussa Frakhani S., Ebrahimi O., Rahmati-yamchi M., Davaran S., (2014), Preparation and characterization of novel electrospun poly(caprolactone)-based nanofibrous scaffolds. Artif. Cells Nanomed. Biotechnol. 44: 504-509.

[29] Zhang J., Li Y., Gao W., Repka M. A., Wang Y., Chen M., (2014), Andrographolide loaded PLGA-PEG-PLGA micelles to improve its bioavailability and anticancer efficacy. Expert. Opin. Drug Deliv. 11: 1367–1380.

[30] Manjili H. K., Malvandi H., Mousavi M. S., Attari E., Danafar H., (2018), In vitro and in vivo delivery of artemisinin loaded PCL–PEG–PCL micelles and its pharmacokinetic study. Artif. Cells Nanomed. Biotechnol. 46: 1-11.

[31] Zhang L., Chen Z., Wang H., Wu S., Zhao K., Sun H., Kong D., Wang C., Leng X., Zhu D., (2016), Preparation and evaluation of PCL–PEG–PCL polymeric nanoparticles for doxorubicin delivery against breast cancer. RSC Adv. 6: 54727-54732.

[32] Dhanavel S., Praveena P., Narayanan V., Stephen A., (2020), Chitosan/reduced graphene oxide/Pd nanocomposites for co-delivery of 5-fluorouracil and curcumin towards HT-29 colon cancer cells. Polym. Bull. 77: 5681–5696.

[33] Vakilinezhad M. A., Amini A., Dara T., Alipour S., (2019), Methotrexate and curcumin co-encapsulated PLGA nanoparticles as a potential breast cancer therapeutic system: In vitro and in vivo evaluation. Colloids Surf. B. 184: 110515-110519.