• International Journal of Technology (IJTech)
  • Vol 12, No 3 (2021)

Facile Fabrication of Polyelectrolyte Complex Nanoparticles Based on Chitosan – Poly-2-Acrylamido-2-Methylpropane Sulfonic Acid as a Potential Drug Carrier Material

Facile Fabrication of Polyelectrolyte Complex Nanoparticles Based on Chitosan – Poly-2-Acrylamido-2-Methylpropane Sulfonic Acid as a Potential Drug Carrier Material

Title: Facile Fabrication of Polyelectrolyte Complex Nanoparticles Based on Chitosan – Poly-2-Acrylamido-2-Methylpropane Sulfonic Acid as a Potential Drug Carrier Material
Arie Wibowo, Agus Jatmiko, Muhammad Bagas Ananda, Systi Adi Rachmawati, Husaini Ardy, Akfiny Hasdi Aimon, Ferry Iskandar

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Cite this article as:
Wibowo, A., Jatmiko, A., Ananda, M.B., Rachmawati, S.A., Ardy, H., Aimon, A.H., Iskandar, F., 2021. Facile Fabrication of Polyelectrolyte Complex Nanoparticles Based on Chitosan – Poly-2-Acrylamido-2-Methylpropane Sulfonic Acid as a Potential Drug Carrier Material. International Journal of Technology. Volume 12(3), pp. 561-570

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Arie Wibowo 1. Material Science and Engineering Research Group, Faculty of Mechanical and Aerospace Engineering, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132, Indonesia 2. Research Center for Nan
Agus Jatmiko Material Science and Engineering Research Group, Faculty of Mechanical and Aerospace Engineering, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132, Indonesia
Muhammad Bagas Ananda Material Science and Engineering Research Group, Faculty of Mechanical and Aerospace Engineering, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132, Indonesia
Systi Adi Rachmawati Material Science and Engineering Research Group, Faculty of Mechanical and Aerospace Engineering, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132, Indonesia
Husaini Ardy Material Science and Engineering Research Group, Faculty of Mechanical and Aerospace Engineering, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132, Indonesia
Akfiny Hasdi Aimon Department of Physics, Faculty of Mathematical and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132, Indonesia
Ferry Iskandar 1. Research Center for Nanosciences and Nanotechnology, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132, Indonesia 2. Department of Physics, Faculty of Mathematical and Natural Sciences, In
Email to Corresponding Author

Abstract
Facile Fabrication of Polyelectrolyte Complex Nanoparticles Based on Chitosan – Poly-2-Acrylamido-2-Methylpropane Sulfonic Acid as a Potential Drug Carrier Material

Polyelectrolyte complexes (PECs) are attractive materials for drug delivery application as they offer simple preparations and high drug-loading efficiency. In this study, a novel method for preparing polyelectrolyte complex nanoparticles using a simple mixing method of chitosan and poly-2-acrylamido-2-methylpropane sulfonic acid (PAMPS) solutions is presented. The effect of chitosan concentrations was examined by fixing the PAMPS concentration at 0.01 %w/v, while chitosan concentrations were varied from 0.01 to 0.05 %w/v. Based on dynamic light scattering (DLS) and zeta sizer results, increasing the chitosan concentration led to increased average PEC particle sizes with broader particle distributions from 249.1 (polydispersity index/PDI 0.13) to 318.2 nm (PDI 0.19) and changed the particle surface charges from -5.85±0.34 to 11.95±0.84 mV. The addition of glutaraldehyde (GA) followed by dialysis eliminated sodium chloride (NaCl) and produced spherical PEC nanoparticles, confirmed via scanning electron microscopy (SEM) results. Among those samples, PECs with a chitosan concentration of 0.01 %w/v are the most promising drug carrier materials due to their negative surface charges, which promote prolonged circulation time in the bloodstream.

Chitosan; Drug carrier; Glutaraldehyde; PAMPS; Polyelectrolyte complex

Introduction

Recently, the utilization of nanoparticles as a drug carrier to minimize undesirable chemotherapeutic side effects has attracted researchers' attention because of their ability to selectively accumulate in tumor tissues through enhanced permeability and retention (EPR) effects (Alsehli, 2020). Many nanoparticles have been used as drug carriers for drug delivery systems (DDS), such as liposomes (Vahed et al., 2017),  dendrimers (Madaan et al., 2014), hydroxyapatite-based nanoparticles (Prasanna and Venkatasubbu, 2018), porous polyion complexes (PICs) (Wibowo et al., 2014), and polyelectrolyte complexes (PECs) (Zhang et al., 2016). One promising drug nanocarrier material is polyelectrolyte complexes.

      PECs are reportedly very useful for nano- or micro-encapsulation and controlled drug release because of their simple preparation, low toxicity, and prolonged circulation time in the bloodstream (Meka et al., 2017).

PECs are prepared from two opposite-charge polyelectrolytes, polycations (positively charged polymers) and polyanions (negatively charged polymers), which assemble complexes via electrostatic interactions in the form of a dense phase that is separated from the solvent (Jha et al., 2014; Meka et al., 2017). Numerous positively charged polymers can be used for PEC formation, such as chitosan, polyethyleneimine (PEI), poly-L-Iysine (PLL), and poly(amidoamine) (PAMAM; (Kim et al., 2016). Chitosan is an excellent candidate for creating PECs for biomedical applications because of its good biocompatibility, very low toxicity, non-immunogenic nature, and numerous hydroxyl and amino functional groups. These properties enhance the conducting reactions, providing unique biological functions and polyelectrolyte formations (Usman et al., 2018; Anirudhan and Nair, 2019). Considering the above properties, chitosan could be orally applied as a micro- or nano-particle for bioactive compound delivery, enzyme immobilization, and as a drug carrier (Hamzah et al., 2019; Krisanti et al., 2019). Many reports also stated that chitosan could form complexes with various polyanions (Antunes et al., 2011; Arora et al., 2011; Luo and Wang, 2014). Several kinds of polyanion are frequently used to form PECs, such as poly-2-acrylamido-2-methylpropane sulfonic acid (PAMPS), alginate, and poly(methacrylic acid) (PMMA). PAMPS is appealing and negatively charges polysulfonated polymers for biomedical applications by acting as a heparin-like polymer with low toxic effects (García-Fernández et al., 2010). PAMPS has been reported as one of the most potent angiogenesis inhibitors (García-Fernández et al., 2010) and can be utilized as an effective cytokine growth factor (Platt et al., 2014). Hence, chitosan and PAMPS are presumably excellent candidates for PEC formation.

Zhang et al. (Zhang et al., 2016) have been prepared chitosan and PAMPS based PECs nanoparticles for controlled delivery of doxorubicin (DOX). The result showed that the average diameter of obtained PECs is 255–390 nm, with an enhanced drug loading rate. However, they used multiple steps of the polymer-monomer pair reaction system to form their PECs. In our previous work, chitosan-PAMPS based PECs has successfully prepared by simple mixing of  PAMPS solution and chitosan solution in sodium chloride (NaCl) (Wibowo et al., 2018; Wibowo et al., 2019). This method offers a simpler and faster strategy for obtaining chitosan-PAMPS-based PECs as they can be prepared directly from their polymer solution. However, the particle size of obtained PECs with a PAMPS concentration of 0.1 %w/v was in the micrometer range (Wibowo et al., 2018), which was too large. As such, it needed to be reduced for cancer-drug carrier application. Preparation of PECs at a lower concentration of the precursors might be an option to solve this problem because Kulkarni et al. (2016) were reported that the particle size of PECs could be significantly decreased by slightly reducing precursor concentrations. Herein, we report the successful fabrication of PEC nanoparticles in an aqueous medium with a physiologically relevant concentration of salt (150 mM NaCl), prepared using a simple polymer solution mixing method at a lower PAMPS concentration (0.01 %w/v). Optimization was carried out by varying chitosan concentrations—0.01; 0.025, and 0.05 %w/v—and investigating their effects on PEC properties—particle sizes, surface charge, and morphologies. This research finding provides an alternative strategy for the preparation of PEC nanoparticles with potency as drug carrier materials.

Conclusion

    Polyelectrolyte complex nanoparticles based on chitosan and PAMPS were successfully prepared using a simple polymer solution mixing method with a PAMPS concentration of 0.01 %w/v and chitosan concentration variations of 0.01–0.05 %w/v. However, increasing the chitosan concentration led to larger particles with broader particle distributions due to chitosan’s rigidity. PECs with a chitosan concentration of 0.01 %w/v were better options for cancer drug carriers than other PEC samples due to their negative surface charges. The addition of GA, followed by dialysis, preserved PEC morphologies and removed NaCl as impurities in the PEC solutions.

Acknowledgement

    The authors would like to acknowledge the funding provided by the Basic Research Fund 2020 from the Indonesian Ministry for Research, Technology, and Higher Education (No. 2/AMD/E1/KP.PTNBH/2020). The authors would also like to recognize the Research Centre for Nanoscience and Nanotechnology, Institut Teknologi Bandung, for utilization of their characterization facilities. Last but not least, the authors would like to express their gratitude to Wiji Rahayu from PT. DKSH Indonesia for DLS measurements, Chairani Tiara Sayyu, Elaeis Hafsah Jauhari, Faisal Ridwansyah Prawira for their assistance, and Dr. Afriyanti Sumboja for her fruitful discussions.

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