Dual-drugs-loaded polymeric nanoparticles formulation design based on response surface methodology of particle size and zeta potential

Benchawan  Chamsai; Praneet  Opanasopit; Wipada  Samprasit

Authors

Benchawan Chamsai Department of Pharmaceutical Technology, College of Pharmacy, Rangsit University, Patumthani 12000, Thailand.
Praneet Opanasopit Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Wipada Samprasit Department of Pharmaceutical Technology, College of Pharmacy, Rangsit University, Patumthani 12000, Thailand.

Keywords:

Box-Behnken Design, dual-drugs, nanoparticles, optimization, particle size, zeta potential

Abstract

Nanoparticles (NPs), particles with at least one dimension below 1000 nm, are frequently used for drug delivery applications. The particle size and zeta potential of NPs can be controlled by the various formulations and processing factors. The purpose of this present study was to optimize dual-drugs (α-mangostin (M) and resveratrol (R))-loaded polymeric NPs. Chitosan (CS) and sodium alginate (ALG) were used to form the NPs via an ionotropic gelation method. A 4-factor, 3-level Box-Behnken Design was conducted for the optimization, choosing the concentrations of CS and ALG and the M and R content as the independent variables. The dependent variables were the particle size and zeta potential of the NPs. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The results found that the M and R-loaded CS/ALG NPs were successfully prepared by the ionotropic gelation method, and the CS and ALG had the potential to be used as carriers for the M and R. The ALG concentration affected the particle size of the NPs, while the zeta potential was affected by the CS and ALG concentrations. The M and R content insignificantly affected the particle size and zeta potential of the NPs. The optimized NPs were determined as CS ranging from 0.050 to 0.075 % w/v, ALG ranging from 0.025 to 0.050 % w/v, M ranging from 2.0 to 2.5 % w/w, and R ranging from 1.5 to 2.5 % w/w. Thus, the optimal CS and ALG concentrations and M and R content of the NPs have the potential to be NP carriers for dual-drugs delivery. These NPs might be beneficial for the transdermal and oral delivery of dual-drugs as active antioxidant, antimicrobial and cytotoxic agents.

References

Atkinson, A. C., & Donev, A. N. (1992). Optimum experimental designs. Oxford, United Kingdom: Oxford University Press.

Bal, Y. (2019). Chapter 11 - Nanomaterials for drug delivery: recent developments in spectroscopic characterization. Characterization and biology of nanomaterials for drug delivery (pp. 281-336). DOI: https://doi.org/10.1016/B978-0-12-814031-4.00011-8. Mohapatra, S. S., Ranjan, S., Dasgupta, N., Mishra, R. K., & Thomas, S. Amsterdam, Netherlands: Elsevier.

Banerjee, A., Qi, J., Gogoi, R., Wong, J., & Mitragotri, S. (2016). Role of nanoparticle size, shape and surface chemistry in oral drug delivery. Journal of Controlled Release, 238, 176-185. DOI: https://doi.org/10.1016/j.jconrel.2016.07.051

Chen, W., Palazzo, A., Hennink, W. E., & Kok, R. J. (2017). Effect of particle size on drug loading and release kinetics of gefitinib-loaded PLGA microspheres. Molecular Pharmaceutics, 14(2), 459-467. DOI: https://doi.org/10.1021/acs.molpharmaceut.6b00896

De, S., & Robinson, D. (2003). Polymer relationships during preparation of chitosan-alginate and poly-l-lysine-alginate nanospheres. Journal of Controlled Release, 89(1), 101-112. DOI: https://doi.org/10.1016/S0168-3659(03)00098-1

Deshmukh, R. K., & Naik, B. (2013). Diclofenac sodium-loaded Eudragit® microspheres: Optimization using statistical experimental design. Journal of Pharmaceutical Innovation, 8, 276-287. DOI: https://doi.org/10.1007/s12247-013-9167-9

Elzoghby, A. O., Freag, M. S., & Elkhodairy, K. A. (2018). Chapter 7 - Biopolymeric nanoparticles for targeted drug delivery to brain tumors. Nanotechnology-based targeted drug delivery systems for brain tumors (pp. 169-190). DOI: https://doi.org/10.1016/B978-0-12-812218-1.00007-5. Kesharwani, P., & Gupta, U. London, United Kingdom: Academic Press.

Gaikwad, V. L., Choudhari, P. B., Bhatia, N. M. & Bhatia, M. S. (2019). Chapter 2 - Characterization of pharmaceutical nanocarriers: in vitro and in vivo studies. Nanomaterials for drug delivery and therapy (pp. 32-58). DOI: https://doi.org/10.1016/B978-0-12-816505-8.00016-3. Grumezescu, A. M. Amsterdam, Netherlands: Elsevier.

Giri, T. K. (2019). Chapter 15 - Chitosan based nanoparticulate system for controlled delivery of biological macromolecules. Nanomaterials for drug delivery and therapy (pp. 435-459). DOI: https://doi.org/10.1016/B978-0-12-816505-8.00004-7. Grumezescu, A. M. Amsterdam, Netherlands: Elsevier.

Joseph, E. & Gautam, S. (2019). Chapter 4 - Multifunctional nanocrystals for cancer therapy: a potential nanocarrier. Nanomaterials for drug delivery and therapy (pp. 91-116). DOI: https://doi.org/10.1016/B978-0-12-816505-8.00007-2. Grumezescu, A. M. Amsterdam, Netherlands: Elsevier.

Kumar, A., & Dixit, C. K. (2017). 3 - Methods for characterization of nanoparticles. Advances in Nanomedicine for the Delivery of Therapeutic Nucleic Acids (pp. 43-58). DOI: https://doi.org/10.1016/B978-0-08-100557-6.00003-1. Nimesh, S., Chandra, R., & Gupta, N.Duxford, United Kingdom: Woodhead Publishing.

Kumari, A., Yadav, S. K., & Yadav, S. C. (2010). Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and Surfaces B: Biointerfaces, 75(1), 1-18. DOI: https://doi.org/10.1016/j.colsurfb.2009.09.001

Lalatsa, A., Leite, D. M., Figueiredo, M. F., & O’Connor, M. (2018). Chapter 5 - Nanotechnology in brain tumor targeting: efficacy and safety of nanoenabled carriers undergoing clinical testing. Nanotechnology-based targeted drug delivery systems for brain tumors (pp. 111-145). DOI: https://doi.org/10.1016/B978-0-12-812218-1.00005-1. Kesharwani, P., & Gupta, U. London, United Kingdom: Academic Press.

Masalova, O., Kulikouskaya, V., Shutava, T., & Agabekov, V. (2013). Alginate and chitosan gel nanoparticles for efficient protein entrapment. Physics Procedia, 40, 69-75. DOI: https://doi.org/10.1016/j.phpro.2012.12.010

Mukhopadhyay, P., Chakraborty, S., Bhattacharya, S., Mishra, R., & Kundu, P. P. (2015). pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery. International Journal of Biological Macromolecules, 72, 640-648. DOI: https://doi.org/10.1016/j.ijbiomac.2014.08.040

Nanjwadem, B. K., Sarkar, A. B., & Srichana, T. (2019). Chapter 12 - Design and characterization of nanoparticulate drug delivery. Characterization and biology of nanomaterials for drug delivery (pp. 337-350). DOI: https://doi.org/10.1016/B978-0-12-814031-4.00012-X. Mohapatra, S.S., Ranjan, S., Dasgupta, N., Mishra, R. K., & Thomas, S. Amsterdam, Netherlands: Elsevier.

National Center for Biotechnology Information. (n.d.). PubChem Database. alpha-Mangostin, CID=5281650. Retrieved May 29, 2020, from https://pubchem.ncbi.nlm.nih.gov/compound/alpha-Mangostin

National Center for Biotechnology Information. (n.d.). PubChem Database. Resveratrol, CID=445154. Retrieved May 29, 2020, from https://pubchem.ncbi.nlm.nih.gov/compound/Resveratrol

Niizawa, I., Espinaco, B. Y., Zorrilla, S. E., & Sihufe, G. A. (2019). Natural astaxanthin encapsulation: Use of response surface methodology for the design of alginate beads. International Journal of Biological Macromolecules, 121, 601-608. DOI: https://doi.org/10.1016/j.ijbiomac.2018.10.044

Nimesh, S., & Gupta, N. (2017). 1 - Nanomedicine for delivery of therapeutic molecules. Advances in Nanomedicine for the Delivery of Therapeutic Nucleic Acids (pp. 1-12). DOI: https://doi.org/10.1016/B978-0-08-100557-6.00001-8. Nimesh, S., Chandra, R., & Gupta, N. Duxford, United Kingdom: Woodhead Publishing.

Obolskiy, D., Pischel, I., Siriwatanametanon, N., & Heinrich, M. (2009). Garcinia mangostana L.: a phytochemical and pharmacological review. Phytotheray Research, 23(8), 1047-1065. DOI: https://doi.org/10.1002/ptr.2730

Prabaharan, M., & Mano, J. F. (2005). Chitosan-based particles as controlled drug delivery systems. Drug Delivery, 12(1), 41-57. DOI: https://doi.org/10.1080/10717540590889781

Pridgen, E. M., Alexis, F., & Farokhzad, O. C. (2014). Polymeric nanoparticle technologies for oral drug delivery. Clinical Gastroenterology and Hepatology, 12(10), 1605-1610. DOI: https://doi.org/10.1016/j.cgh.2014.06.018

Rizvi, S. A. A., & Saleh, A. M. (2018). Applications of nanoparticle systems in drug delivery technology. Saudi Pharmaceutical Journal, 26(1), 64-70. DOI: https://doi.org/10.1016/j.jsps.2017.10.012

Rowe, R. D., Sheskey, P. J., & Owen, S. C. (2009). Handbook of Pharmaceutical Excipient, London: United Kingdom: Pharmaceutical Press.

Samprasit, W., Akkaramongkolporn, P., Jaewjira, S., & Opanasopit, P. (2018). Design of alpha mangostin-loaded chitosan/alginate controlled-release nanoparticles using genipin as crosslinker. Journal of Drug Delivery Science and Technology, 46, 312-321. DOI: https://doi.org/10.1016/j.jddst.2018.05.029

Samprasit, W., Akkaramongkolporn, P., Sutananta, W., & Opanasopit, P. (2017). Effects of chitosan and alginate concentrations on particle size and zeta potential of chitosan- alginate micro/nanoparticles containing α-mangostin. Bulletin of health science and technology, 15(supplement), 72-73. https://www.researchgate.net/publication/342833371

Selvamani, V. (2019). Chapter 15 - Stability Studies on nanomaterials used in drugs. Characterization and biology of nanomaterials for drug delivery (pp. 425-444). DOI: https://doi.org/10.1016/B978-0-12-814031-4.00015-5. Mohapatra, S. S., Ranjan, S., Dasgupta, N., Mishra, R. K., & Thomas, S. Amsterdam, Netherlands: Elsevier.

Sharma, D., Maheshwari, D., Philip, G., Rana, R., Bhatia, S., Singh, M., Gabrani, R., Sharma, S. K., Ali, J., Sharma, R. K., & Dang, S. (2014). Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using Box-Behnken Design: In vitro and in vivo evaluation. BioMed Research International, 2014, Article ID 156010. DOI: https://doi.org/10.1155/2014/156010

Vinothini, K., & Rajan, M., (2019). Chapter 9 - Mechanism for the nano-based drug delivery system. Characterization and biology of nanomaterials for drug delivery (pp. 219-263). DOI: https://doi.org/10.1016/B978-0-12-814031-4.00009-X. Mohapatra, S.S., Ranjan, S., Dasgupta, N., Mishra, R. K., & Thomas, S. Amsterdam, Netherlands: Elsevier.

Wang, G., Wang, Z., Li, C., Duan, G., Wang, K., Li, Q., & Tao, T. (2018). RGD peptide-modified, paclitaxel prodrug-based, dual-drugs loaded, and redox-sensitive lipid-polymer nanoparticles for the enhanced lung cancer therapy. Biomedicine & Pharmacotherapy, 106, 275-284. DOI: https://doi.org/10.1016/j.biopha.2018.06.137

Wu, L., Zhang, J., & Watanabe, W. (2011). Physical and chemical stability of drug nanoparticles. Advanced Drug Delivery Reviews, 63(6), 456-469. DOI: https://doi.org/10.1016/j.addr.2011.02.001

Yadav, H. K. S., Dibi, M., Mohammed, A., & Emad, A. (2019). Chapter 13 - Thermoresponsive drug delivery systems, characterization, and applications. Characterization and biology of nanomaterials for drug delivery (pp. 351-373). DOI: https://doi.org/10.1016/B978-0-12-814031-4.00013-1. Mohapatra, S.S., Ranjan, S., Dasgupta, N., Mishra, R.K., & Thomas, S. Amsterdam, Netherlands: Elsevier.