Enhanced Drug Release of Poly(lactic-co-glycolic Acid) Nanoparticles Modified with Hydrophilic Polymers: Chitosan and Carboxymethyl Chitosan

https://doi.org/10.22146/ijc.73673

Diah Lestari(1), Noverra Mardhatillah Nizardo(2*), Kamarza Mulia(3)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok 16424, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok 16424, Indonesia
(3) Department of Chemical Engineering, Universitas Indonesia, Depok 16424, Indonesia
(*) Corresponding Author

Abstract


The biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) is a biomaterial with great potential as a drug delivery carrier and a tissue engineering scaffold. Using diclofenac sodium (DS) as a drug model, PLGA/DS nanoparticles were synthesized by modification with two hydrophilic polymers: chitosan and carboxymethyl chitosan (CMCh). The introduction of chitosan and CMCh enhances the efficiency encapsulation, capacity loading of the nanoparticles, and DS release at pH 6.8 and minimum release at pH 1.2. Synthesis of nanoparticles was carried out using a double emulsion (water/oil/water) solvent evaporation method. Characterization using an Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrophotometer indicates that the interaction between DS and polymer on nanoparticles is non-covalent with a spherical shape based on a transmission electron microscope (TEM) and scanning electron microscope (SEM) characterization. From the various formulation studied, nanoparticles with the ratio chitosan-PLGA-DS and CMCh-PLGA-DS of 2:20:4 proved to be the optimum model carrier with the required release profile and could be the alternative for DS delivery systems.


Keywords


diclofenac sodium; PLGA; chitosan; carboxymethyl chitosan; controlled release

Full Text:

Full Text PDF


References

[1] Hasnain, M.S., Rishishwar, P., Rishishwar, S., Ali, S., and Nayak, A.K., 2018, Isolation and characterization of Linum usitatisimum polysaccharide to prepare mucoadhesive beads of diclofenac sodium, Int. J. Biol. Macromol., 116, 162–72.

[2] Yurtdaş-Kırımlıoğlu, G., and Görgülü, Ş., 2021, Surface modification of PLGA nanoparticles with chitosan or Eudragit® RS 100: Characterization, prolonged release, cytotoxicity, and enhanced antimicrobial activity, J. Drug Delivery Sci. Technol., 61, 102145.

[3] Altman, R., Bosch, B., Brune, K., Patrignani, P., and Young, C., 2015, Advances in NSAID development: Evolution of diclofenac products using pharmaceutical technology, Drugs, 75 (8), 859–77.

[4] Cooper, D.L., and Harirforoosh, S., 2014, Design and optimization of PLGA-based diclofenac loaded nanoparticles, PLoS One, 9 (1), e87326.

[5] Yadav, H.K.S., and Shivakumar, H.G., 2012, In vitro and in vivo evaluation of pH-sensitive hydrogels of carboxymethyl chitosan for intestinal delivery of theophylline, Int. Scholarly Res. Not., 2012, 763127.

[6] Sequeira, J.A.D., Pereira, I., Ribeiro, A.J., Veiga, F., and Santos, A.C., 2020, "Surface Functionalization of PLGA Nanoparticles for Drug Delivery" in Handbook of Functionalized Nanomaterials for Industrial Applications, Eds. Mustansar Hussain, C., Elsevier, Amsterdam, Netherlands, 185–203.

[7] Deng, Y., Zhang, X., Shen, H., He, Q., Wu, Z., Liao, W., and Yuan, M., 2020, Application of the nano-drug delivery system in treatment of cardiovascular diseases, Front. Bioeng. Biotechnol., 7, 489.

[8] Bhattacharjee, S., 2019, "Polymeric Nanoparticles" in Principles of Nanomedicine, Jenny Stanford Publishing, Singapore, 195–240.

[9] Varga, N., Hornok, V., Janovák, L., Dékány, I., and Csapó, E., 2019, The effect of synthesis conditions and tunable hydrophilicity on the drug encapsulation capability of PLA and PLGA nanoparticles, Colloids Surf., B, 176, 212–218.

[10] Sharifi, F., Atyabi, S.M., Norouzian, D., Zandi, M., Irani, S., and Bakhshi, H., 2018, Polycaprolactone/carboxymethyl chitosan nanofibrous scaffolds for bone tissue engineering application, Int. J. Biol. Macromol., 115, 243–248.

[11] Khanal, S., Adhikari, U., Rijal, N.P., Bhattarai, S.R., Sankar, J., and Bhattarai, N., 2016, pH-Responsive PLGA nanoparticle for controlled payload delivery of diclofenac sodium, J. Funct. Biomater., 7 (3), 21.

[12] Shanavas, A., Jain, N.K., Kaur, N., Thummuri, D., Prasanna, M., Prasad, R., Naidu, V.G.M., Bahadur, D., and Srivastava, R., 2019, Polymeric core-shell combinatorial nanomedicine for synergistic anticancer therapy, ACS Omega, 4 (22), 19614–19622.

[13] Simonazzi, A., Cid, A.G., Villegas, M., Romero, A.I., Palma, S.D., and Bermúdez, J.M., 2018, "Nanotechnology Applications in Drug Controlled Release" in Drug Targeting and Stimuli Sensitive Drug Delivery Systems, Eds. Grumezescu, A.M., William Andrew Publishing, Oxford, UK, 81–116.

[14] Khadka, P., Ro, J., Kim, H., Kim, I., Kim, J.T., Kim, H., Cho, J.M., Yun, G., and Lee, J., 2014, Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability, Asian J. Pharm. Sci., 9 (6), 304–316.

[15] Wang, J., Wang, F., Li, X., Zhou, Y., Wang, H., and Zhang, Y., 2019, Uniform carboxymethyl chitosan-enveloped Pluronic F68/poly(lactic-co-glycolic acid) nano-vehicles for facilitated oral delivery of gefitinib, a poorly soluble antitumor compound, Colloids Surf., B, 177, 425–432.

[16] Stuart, B.H., 2004, Infrared Spectroscopy: Fundamentals and Applications, John Wiley & Sons, Chichester, UK.

[17] Al-Nemrawi, N.K., Alshraiedeh, N.H., Zayed, A.L., and Altaani, B.M., 2018, Low molecular weight chitosan-coated PLGA nanoparticles for pulmonary delivery of tobramycin for cystic fibrosis, Pharmaceuticals, 11 (1), 28.

[18] Joshi, J.M., and Sinha, V.K., 2006, Synthesis and characterization of carboxymethyl chitosan grafted methacrylic acid initiated by ceric ammonium nitrate, J. Polym. Res., 13 (5), 387–395.

[19] Javadzadeh, Y., Ahadi, F., Davaran, S., Mohammadi, G., Sabzevari, A., and Adibkia, K., 2010, Preparation and physicochemical characterization of naproxen-PLGA nanoparticles, Colloids Surf., B, 81 (2), 498–502.

[20] Moku, G., Gopalsamuthiram, V.R., Hoye, T.R., and Panyam, J., 2019, "Surface Modification of Nanoparticles: Methods and Applications" in Surface Modification of Polymers: Methods and Applications, Eds. Pinson, J., and Thiry, D., Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 317–446.

[21] Al-Nemrawi, N.K., Okour, A.R., and Dave, R.H., 2018, Surface modification of PLGA nanoparticles using chitosan: Effect of molecular weight, concentration, and degree of deacetylation, Adv. Polym. Technol., 37 (8), 3066–3075.

[22] Guo, C., and Gemeinhart, R.A., 2008, Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles, Eur. J. Pharm. Biopharm., 70 (2), 597–604.

[23] Ab El Hady, W.E., Mohamed, E.A., Soliman, O.A.E., and El-Sabbagh, H.M., 2019, In vitro-in vivo evaluation of chitosan-PLGA nanoparticles for potentiated gastric retention and anti-ulcer activity of diosmin, Int. J. Nanomed., 14, 7191–7213.

[24] Cerqueira, B.B.S., Lasham, A., Shelling, A.N., and Al-Kassas, R., 2017, Development of biodegradable PLGA nanoparticles surface engineered with hyaluronic acid for targeted delivery of paclitaxel to triple negative breast cancer cells, Mater. Sci. Eng., C, 76, 593–600.

[25] Honary, S., and Zahir, F., 2013, Effect of zeta potential on the properties of nano-drug delivery systems - A review (Part 2), Trop. J. Pharm. Res., 12 (2), 265–273.

[26] Wang, Y., Li, P., and Kong, L., 2013, Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery, AAPS PharmSciTech, 14 (2), 585–592.

[27] Betancourt, T., Brown, B., and Brannon-Peppas, L., 2007, Doxorubicin-loaded PLGA nanoparticles by nanoprecipitation: Preparation, characterization and in vitro evaluation, Nanomedicine, 2 (2), 219–232.

[28] Babick, F., 2020, "Dynamic Light Scattering (DLS)" in Characterization of Nanoparticles, Elsevier Inc., Amsterdam, Netherlands, 137–172.

[29] Crucho, C.I.C., and Barros, M.T., 2017, Polymeric nanoparticles: A study on the preparation variables and characterization methods, Mater. Sci. Eng., C, 80, 771–784.

[30] Rizvi, S.A.A., and Saleh, A.M., 2018, Applications of nanoparticle systems in drug delivery technology, Saudi Pharm. J., 26 (1), 64–70.

[31] de Lima, I.A., Khalil, N.M., Tominaga, T.T., Lechanteur, A., Sarmento, B., and Mainardes, R.M., 2018, Mucoadhesive chitosan-coated PLGA nanoparticles for oral delivery of ferulic acid, Artif. Cells, Nanomed., Biotechnol., 46, 993–1002.

[32] Liu, Y., Yang, G., Jin, S., Xu, L., and Zhao, C.X., 2020, Development of high-drug-loading nanoparticles, Chempluschem, 85 (9), 2143–2157.



DOI: https://doi.org/10.22146/ijc.73673

Article Metrics

Abstract views : 2990 | views : 1914


Copyright (c) 2022 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.