Improved Mucoadhesive Properties of Repaglinide-Loaded Nanoparticles: Mathematical Modelling through Machine Learning-Based Approach

Nader Ibrahim Namazi(1*)

(1) Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Al Madinah Al Munawarah 30001, Saudi Arabia
(*) Corresponding Author


This research work aims to develop a modified repaglinide-loaded chitosan-ethyl cellulose nanoparticles (RPG-ECSNPs) as a novel sustained-release dosage form with improved mucoadhesive properties using an emulsification solvent-evaporation technique. The RPG-ECSNPs with different particle sizes were prepared from various polymers containing ethyl cellulose (EC) as the internal phase and chitosan (CS) as the external phase, and the use of surfactants, including Tween 80 and poloxamer 188 as emulsifiers. In vitro drug release, drug loading amount, and entrapment efficiency have been influenced by changes in the concentrations of CS and EC. The mean droplet size and zeta potential of RPG-ECSNPs were 213 ± 8.5 nm and 16.4 ± 2.4 mV, respectively. The optimized formulation's entrapment efficiency was 66 ± 2.3%, and drug loading was 7.9 ± 1.65%. The release profile was significantly higher in PBS (90%) than in diluted hydrochloric acid (30%) during 24 h of the study. The mucoadhesive function of the particles was examined in vitro using part of rat intestines. The highest adhesive % was observed for the chitosan-coated NPs. No adhesive properties were noticed for chitosan-free NPs (P-value > 0.05). This indicated that ECSNPs can be successfully utilized for sustained and controlled drug delivery of RPG through the GIT.


adhesive properties; chitosan; ethyl cellulose; nanoparticles

Full Text:

Full Text PDF


[1] Cho, N.H., Shaw, J.E., Karuranga, S., Huang, Y., da Rocha Fernandes, J.D., Ohlrogge, A.W., and Malanda, B., 2018, IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045, Diabetes Res. Clin. Pract., 138, 271–281.

[2] Röder, P.V., Wu, B., Liu, Y., and Han, W., 2016, Pancreatic regulation of glucose homeostasis, Exp. Mol. Med., 48 (3), e219.

[3] Liu, W.F., Kang, C.Z., Kong, M., Li, Y., Su, J., Yi, A., Cheng, X.J., and Chen, X.G., 2012, Controlled release behaviors of chitosan/α, β-glycerophosphate thermo-sensitive hydrogels, Front. Mater. Sci., 6 (3), 250–258.

[4] Liu, Y., Ma, L., and Gao, C., 2012, Facile fabrication of the glutaraldehyde cross-linked collagen/chitosan porous scaffold for skin tissue engineering, Mater. Sci. Eng., C, 32 (8), 2361–2366.

[5] Young, T.H., Wang, I.J., Hu, F.R., and Tsung, J.W., 2014, Fabrication of a bioengineered corneal endothelial cell sheet using chitosan/polycaprolactone blend membranes, Colloids Surf., B, 116, 403–410.

[6] Hu, H., Tang, C., and Yin, C., 2014, Folate conjugated trimethyl chitosan/graphene oxide nanocomplexes as potential carriers for drug and gene delivery, Mater. Lett., 125, 82–85.

[7] Larbi-Bouamrane, O., Bal, Y., Aliouche, D., Cote, G., and Chagnes, A., 2016, Preparation and characterization of cross-linked chitosan microcapsules for controlled delivery of oxytetracycline, Indian J. Pharm. Sci., 78 (6), 715–724.

[8] Wu, L., Zhao, L., Su, X., Zhang, P., and Ling, G., 2020, Repaglinide-loaded nanostructured lipid carriers with different particle sizes for improving oral absorption: Preparation, characterization, pharmacokinetics, and in situ intestinal perfusion, Drug Delivery, 27 (1), 400–409.

[9] Lee, Y.S., Johnson, P.J., Robbins, P.T., and Bridson, R.H., 2013, Production of nanoparticles-in-microparticles by a double emulsion method: A comprehensive study, Eur. J. Pharm. Biopharm., 83 (2), 168–173.

[10] El-Habashy, S.E., Allam, A.N., and El-Kamel, A.H., 2016, Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: Formulation and in vitro/in vivo evaluation, Int. J. Nanomed., 11, 2369–2380.

[11] Ebrahimi, H.A., Javadzadeh, Y., Hamidi, M., and Jalali, M.B., 2015, Repaglinide-loaded solid lipid nanoparticles: Effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles, Daru, J. Pharm. Sci., 23, 46.

[12] Lokhande, A.B., Mishra, S., Kulkarni, R.D., and Naik, J.B., 2013, Preparation and characterization of repaglinide loaded ethylcellulose nanoparticles by solvent diffusion technique using high pressure homogenizer, J. Pharm. Res., 7 (5), 421–426.

[13] Aghaei, M., Erfani-Moghadam, V., Daneshmandi, L., Soltani, A., Abdolahi, N., Cordani, M., Yahyazadeh, A., Rad, S.M., Tavassoli, S., and Balakheyli, H., 2021, Non-ionic surfactant vesicles as novel delivery systems for sulfasalazine: Evaluation of the physicochemical and cytotoxic properties, J. Mol. Struct., 1230, 129874.

[14] Javed Ansari, M., Aldawsari, M.F., Zafar, A., Soltani, A., Yasir, M., Asadullah Jahangir, M., Taleuzzaman, M., Erfani-Moghadam, V., Daneshmandi, L., Mahmoodi, N.O., Yahyazadeh, A., Lutfor Rahman, M., and Sani Sarjadi, M., 2022, In vitro release and cytotoxicity study of encapsulated sulfasalazine within LTSP micellar/liposomal and TSP micellar/niosomal nano-formulations, Alexandria Eng. J., 61 (12), 9749–9756.

[15] El-Say, K.M., 2016, Maximizing the encapsulation efficiency and the bioavailability of controlled-release cetirizine microspheres using Draper–Lin small composite design, Drug Des., Dev. Ther., 10, 825–839.

[16] Laracuente, M.L., Yu, M.H., and McHugh, K.J., 2020, Zero-order drug delivery: State of the art and future prospects, J. Controlled Release, 327, 834–856.

[17] González, C., Reyes, L.H., Muñoz-Camargo, C., and Cruz, J.C., 2021, Synthesis, characterization, and functionalization of chitosan and gelatin type B nanoparticles to develop novel highly biocompatible cell-penetrating agents, Mater. Proc., 4 (1), 30.

[18] Ghauri, Z.H., Islam, A., Qadir, M.A., Gull, N., Haider, B., Ullah-Khan, R., and Riaz, T., 2021, Development and evaluation of pH-sensitive biodegradable ternary blended hydrogel films (chitosan/guar gum/PVP) for drug delivery application, Sci. Rep., 11, 21255.

[19] Suhail, M., Wu, P.C., and Usman-Minhas, M., 2021, Development and characterization of pH-sensitive chondroitin sulfate-co-poly(acrylic acid) hydrogels for controlled release of diclofenac sodium, J. Saudi Chem. Soc., 25 (4), 101212.

[20] Ways, T.M., Man-Lau, W., and Khutoryanskiy, V.V., 2018, Chitosan and its derivatives for application in mucoadhesive drug delivery systems, Polymers, 10 (3), 267.

[21] Vaghani, S.S., and Patel, M.M., 2011, Hydrogels based on interpenetrating network of chitosan and polyvinyl pyrrolidone for pH-sensitive delivery of repaglinide, Curr. Drug Discovery Technol., 8 (2), 126–135.

[22] Poovi, G., Dhana-Lekshmi, M., Narayanan, N., and Reddy, N., 2011, Preparation and characterization of repaglinide loaded chitosan polymeric nanoparticles, Res. J. Nanosci. Nanotechnol., 1 (1), 12–24.

[23] Zhou, H.Y., Cao, P.P., Zhao, J., Wang, Z.Y., Li, J.B., and Zhang, F.L., 2014, Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres, Front. Mater. Sci., 8 (4), 373–382.


Article Metrics

Abstract views : 820 | views : 296

Copyright (c) 2023 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.

Analytics View The Statistics of Indones. J. Chem.