Release Behavior Of Pickering Emulsion Stabilized With Hydrophobic Alginate/Chitosan Nanocomposites

With the excellent properties of wide range of sources,biocompatibility,biodegradability and pH sensitivity,alginate and chitosan biomaterials?microspheres,etc.?were used as drug carriers,and gradually become a research hotspot in sustained released field.However,the unicity of the microsphere wall structure was prone to cause burst release or uneven release,and no high drug loading,which lead to the reduction of biodegradation and restriction on the medical applications development.In view of the above deficiencies,this paper proposes to stabilize the two-phase interface of emulsion with hydrophobic calcium alginate/chitosan nanocomposite particles?HSA-CS NCs?,and to construct Pickering emulsion with a rigid and pH-responsive mass transfer interface as a liquid controlled release system with high stability and low toxicity,high encapsulation rate and high mass transfer surface area.By studying the effect of Pickering emulsion on the release behavior of ibuprofen,the release rule and release mechanism of the liquid carrier were explored.The main contents and results of this study are listed as follows:In this paper,the sodium alginate?SA?was hydrophobic modified by diacetone acrylamide?DAAM?,and then the hydrophobic calcium alginate particles?HSA-CA?were prepared by double emulsion method.After coating chitosan?CS?,an emulsion stabilizer—hydrophobic calcium alginate/chitosan nanocomposite?HSA-CS NCs?was obtained.The particle size,contact angle and SEM analysis revealed that HSA-CS NCs with spherical in shape,rough surface and good dispersion,a contact angle of 66.93°,and particle diameter of 396 nm under the conditions of 7%?w/v?CaCl₂ and 0.1%?w/v?CS.By controlling the parameters of CaCl₂ concentration,chitosan concentration,oil-water volume ratio,particle concentration,aqueous phase pH and oil phase type,the stability and internal microstructure of the emulsion can be regulated.The results showed that the emulsion has the best stability under conditions of 7%?w/v?CaCl₂,0.1%?w/v?CS,oil-water ratio 1.4:1,particle concentration 3 wt%,water phase pH 7.3 and corn oil,with small droplet size of 2-8 um,regular droplet morphology and dense distribution.The in vitro release behavior of HSA-CS-Pickering emulsions loaded with ibuprofen was investigated by designing different pH gradient release environments.The results showed that in simulated gastric fluid?SGF?,the ibuprofen cumulative release did not exceed 2.5%in 5 h,and the cumulative release in simulated intestinal fluid?SIF?at 5 h was no less than 36.2%;continuous release shown that the emulsion hardly released in SGF,followed by slow release in the first 1 h of the SIF,the later release rate increased,and the continuous release of 30mg/mL ibuprofen reached 88.37%in 24 h.HSA-CS-Pickering emulsion showed excellent pH-responsive controlled-release and sustain-release properties.In vitro drug release kinetic model analysis showed that the release of HSA-CS-Pickering emulsion in SIF was more fitting with the model First order and Peppas-Sahlin.Drug release mechanism was controlled by the synergistic effect of Fickian diffusion and swelling and corrosion of HSA-CS.