Optimization by Central Composite Experimental Design of the Synthesis of Physically Crosslinked Chitosan Spheres.

Sara Isabel Zamora Lagos,José Herminsul Mina Hernández,Jefferson Murillo Salas,Carlos David Grande Tovar,Mayra Eliana Valencia Zapata

doi:10.3390/biomimetics5040063

Sara Isabel Zamora Lagos, José Herminsul Mina Hernández + Show 3 more

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https://doi.org/10.3390/biomimetics5040063

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Abstract

Chitosan (CS) has special properties such as biocompatibility, biodegradability, antibacterial, and biological activity which make this material is currently studied in various applications, including tissue engineering. There are different methods to modify the morphology of CS. Most use chemical crosslinking agents, however, those methods have disadvantages such as low polymer degradability and unwanted side effects. The objective of this research was to obtain CS spheres through the physical crosslinking of commercial CS without using crosslinking agents through a simple coacervation method. A central composite experimental design was used to optimize the synthesis of the CS spheres and by the response surface methodology it was possible to obtain CS spheres with the smallest diameter and the most regular morphology. With the optimal formulation (CS solution 1.8% (w/v), acetic acid (AAC) solution 1% (w/v), sodium hydroxide (NaOH) solution 13% (w/v), relative humidity of (10%) and needle diameter of 0.6 mm), a final sphere diameter of 1 mm was obtained. Spheres were characterized by physical, chemical, thermal, and biological properties in simulated body fluid (SBF). The results obtained allowed us to understand the effect of the studied variables on the spheres’ diameter. An optimized condition facilitated the change in the morphology of the CS while maintaining its desirable properties for use in tissue engineering.

Highlights

Chitosan (CS) is a partially deacetylated derivative of chitin with biodegradation, biocompatibility, and bioactivity properties that make it attractive for biomedical applications and various dental applications [1].CS can be prepared with different morphologies such as sponges, fibers, films, and other complex structures such as microspheres [2]
There are investigations related to CS spheres prepared by different methods, in this study, we focus on the physical crosslinking of CS spheres by the simple coacervation method, looking for a statistical model that allows obtaining CS spheres with a small diameter and regular morphology
Synthesis of CS spheres was performed using the coacervation methodology, which consisted in the addition of a low concentration (1% w/v) solution of CS flakes dissolved in diluted acetic acid (AAC) (1.8% w/v) to a NaOH solution (13% w/v) dropwise, under gentle stirring

Summary

Introduction

CS can be prepared with different morphologies such as sponges, fibers, films, and other complex structures such as microspheres [2]. CS spheres are widely applied in many fields because of their special sizes and different forms and composition. CS spheres can be functionalized or crosslinked with chemical agents, either to modify their chemical properties such as the addition of active components like antibiotics, curcumin or zinc oxide, or to maintain their initial morphology such as the addition of crosslinking agents like glutaraldehyde or sodium tripolyphosphate [3,4,5,6,7]. Crosslinking mainly improves mechanical properties and increases polymer stability by interconnecting molecules. It simultaneously reduces the number of available functional

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