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Preparation and optimization of controlled release nanoparticles containing cefixime using Central Composite design: An attempt to enrich its antimicrobial activity


Mohammad Ali Mahjoub, Pedram Ebrahimnejad*, Fatemeh Shahlaee, Pouneh Ebrahimi and Zaynab Sadeghi-Ghadi  


Background: Due to the increased resistance against existing antibiotics, research is essential to discover new and alternative ways to control infections induced by resistant pathogens.

Objective: The goal of the current scrutinization was to enrich the dissolution rate and antibacterial property of cefixime (CEF) orally.

Methods: To achieve the desired results, chitosan nanoparticles (NPs) containing CEF were fabricated using the ionic gelation method. Central Composite design has been applied to get the optimal formulation for the delivery of CEF. The effect of three variables such as the concentration of chitosan, tripolyphosphate, and tween 80 on the characteristics of NPs was evaluated.

Results: The optimized NPs were a relatively monodispersed size distribution with an average diameter of 193 nm and a zeta potential of about 11 mV. The scanning tunneling microscope confirmed the size of NPs. The surface morphology of NPs was observed by scanning electron microscopy. The calorimetric analysis indicated the amorphous state of cefixime in the formulation. The dissolution rate of NPs in aqueous media was acceptable and the model of release kinetic for CEF from NPs followed the Peppas model. The potency of CEF in NPs against various types of bacteria was hopefully efficient. The ex- vivo release study demonstrated higher penetration of NPs from the rat intestine compared to free drug. The cell culture study showed the safety of the optimized formulation.

Conclusion: It was concluded that CLN could be considered as a prospering system for the controlled delivery of CEF with advantaging its antibacterial effectiveness.


Nanoparticles, chitosan, cefixime, central composite, antibacterial activity, safety


Department of Pharmaceutics, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Islamic Azad University Tehran North Branch, Department of Chemistry, Tehran, Department of Chemistry, Faculty of Sciences, Golestan University, Gorgan, Department of Pharmaceutics, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj

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