Design and Preclinical Evaluation of Chitosan/Kaolin Nanocomposites with Enhanced Hemostatic Efficiency

Abstract

In the current study, hemostatic compositions including a combination of chitosan and kaolin have been developed. Chitosan is a marine polysaccharide derived from chitins, a structural component in the shells of crustaceans. Both chitosan and kaolin have the ability to mediate a quick and efficient hemostatic effect following immediate application to injury sites, and thus they have been widely exploited in manufacturing of hemostatic composites. By combining more than one hemostatic agent (i.e., chitosan and kaolin) that act via more than one mechanism, and by utilizing different nanotechnology-based approaches to enhance the surface areas, the capability of the dressing to control bleeding was improved, in terms of amount of blood loss and time to hemostasis. The nanotechnology-based approaches utilized to enhance the effective surface area of the hemostatic agents included the use of Pluronic nanoparticles, and deposition of chitosan micro- and nano-fibers onto the carrier. The developed composites effectively controlled bleeding and significantly improved hemostasis and survival rates in two animal models, rats and rabbits, compared to conventional dressings and QuikClot® Combat Gauze. The composites were well-tolerated as demonstrated by their in vivo biocompatibility and absence of clinical and biochemical changes in the laboratory animals after application of the dressings.

In-vitro Analysis of Hemostatic Cotton Khadi Dressing with Kaolin/Chitosan-based Composition and Its Application as Prospective Wound Dressing

“…The method to coat the cotton gauze in a heated kaolin solution is conventionally used 26,27 . However, one study result shows that direct coating of kaolin slurry results in low coating efficiency and gives relatively low hemostatic efficiency 28 . To achieve higher hemostatic efficiency and lesser detachment of kaolin from the dressing the Kaolin solution is gradually added to the chitosan solution with continuous heating and stirring the solution.…”

“…Kaolin rapidly promotes blood coagulation by activating the factor XII protein which initiates the coagulation cascade 30,31 . In a previous study, it has been analyzed that the kaolin/chitosan composites showed significantly reduced clotting time and enhanced hemostatic efficiency 28 calculated in two rats after puncturing their leg vein and reapplying hemostatic dressing every 10 seconds until the time when the bleeding stopped. In all the models the respective dressings were applied immediately after the injury with immediate compression.…”

Kaolinite-Chitosan based Nano-Composites and Applications

“…These nanocomposite materials are gaining importance due to their excellent biocompatible properties and not introducing any clinical or biochemical changes after their applications. Studies proved that combining more than one hemostatic agent such as kaolin-chitosan composite have improved the efficiency of bleeding control [22]. This could be due to the increased surface area and multiple components responsible for more than one mechanism in treating wounds.…”

Chitosan Functionalization: Covalent and Non-Covalent Interactions and Their Characterization

“…Interestingly, the mechanical resistance and stability of CS derivatives can be significantly improved by their non-covalent association to specific additives. This strategy was highlighted in bone tissue engineering and wound dressing applications [ 101 , 102 ] and is also suitable for the development of pH-responsive conjugates [ 103 ]. This section describes systems involving non-functionalized CS forming non-covalent interactions with other components including polymers, proteins, small molecules, and nanocomposites.…”

“…SEM can give essential insights into structure porosity, pore size, and roughness degree of hydrogels, nano/micro-fibers, and NPs based on CS [ 31 , 43 ]. The roughness degree is particularly important in applications such as wound healing, where cell attachment and proliferation has to be favored [ 82 , 102 ], or in food packaging, where smooth surfaces are preferred [ 50 ]. SEM is also a method of choice to observe and measure the pores of CS composites and molecular organic framework (MOF) [ 130 , 175 ].…”