Thermoresponsive Pickering Double Emulsions Stabilized By Biodegradable Block Copolymer Micelles And Their Controlled Release

Double emulsion is a kind of special emulsion with "two-membrane and three-phase" multicompartment structure,and its physical stability plays an important role in determining its encapsulation and release performance in practical applications.Herein,biodegradable diblock copolymers with different block compositions and ratios were synthesized by ring-opening polymerization,and their self-assembled micelles were used as particulate emulsifiers.A stable Pickering double emulsion was obtained,and endowed with tunable thermoresponsiveness and controlled release properties.By designing the molecular weights of the polyethylene glycol(PEG)block and the polycaprolactone(PCL)block,a series of PEG-b-PCL diblock copolymers with different ratios of hydrophilic/hydrophobic blocks were synthesized,and the range of PCL block mass fraction was from 41.4%to 94.4%confirmed by 1H NMR.Then self-assembled micelles of block copolymers were prepared by the solvent evaporation method.Combined with transmission electron microscope observation and dynamic light scattering analysis,the micelles were spherical with an average size ranging from 43 to 176 nm.The contact angle test results showed that the wettability of the micelles could be effectively adjusted by the mass fraction of PCL blocks.The emulsifying properties of the micelles were further evaluated by using PEG-b-PCL micelles and a high-speed homogeneous process to emulsify the water phase and medium chain triglycerides.Through microscope observation and phase diagram analysis,the effect of PCL block mass fractions on the emulsion type and microstructure of the formed Pickering emulsion was studied.The results show that in the case of an oil-water volume ratio of 1:1,increasing the mass fraction of the PCL block in the micelles can obtain O/W-type,W/O/W-type,and even W/O-type Pickering emulsions,respectively.The obtained Pickering emulsions all showed good long-term storage stability.To adjust the chain structure and composition of the block copolymer,by introducing valerolactone(VL)as the comonomer of caprolactone(CL),adjusting the feeding ratio of CL/VL monomer,and designing the mass fraction of the hydrophobic block to be 92 wt%,a series of PEG-b-PCVL block copolymers with similar proportions of hydrophilic/hydrophobic blocks but different molar fractions of VL units in the hydrophobic block(0%-39.8%).The adjustment range of Tm of PEG-b-PCVL block copolymer was found to be 22.2-55.8℃ by differential scanning calorimetry(DSC)analysis.The effects of CL/VL unit ratio of hydrophobic PEG-b-PCVL micelles,emulsification temperature,micelle content and shearing speed on the formation and properties of W/O Pickering emulsions were studied.For the PEGb-PCVL micellar emulsification system with defined composition,there is a definite phase transition temperature(PIT).When the temperature is lower than this temperature,a W/O Pickering emulsion can be obtained after emulsification,and when the temperature is higher than this temperature,the phase inversion of the emulsification system will occur.In the range of 0%to 25.5%mole fraction of VL units,the PIT of the emulsified system decreased with the increase of the mole fraction of VL units.However,when the molar fraction of VL units reaches 39.8%,there is no phase transition behavior in the emulsified system.The resulting W/O Pickering emulsion exhibits good stability at lower temperatures,and raising the temperature above the melting point of the micelles can trigger the rapid response of the W/O Pickering emulsion and its complete demulsification,so the thermal responsiveness of the W/O Pickering emulsions was achieved.Amphiphilic PEG-b-PCVL diblock copolymers with different proportions of hydrophilic/hydrophobic blocks(PCVL block mass fraction is from 64.7%to 94.2%)but substantially the same molar ratio of CL/VL units(8/2)were further synthesized,and their selfassembled micelles were used as particle emulsifiers.After "one-step" emulsification,a W/O/W-type Pickering double emulsion was obtained,and its temperature responsiveness and controlled release properties were successfully endowed.The results of DSC analysis confirmed that the melting temperatures of these semicrystalline PEG-b-PCVL copolymers were all in the range of 33.8-38.4℃,close to the range of physiological temperature.By adjusting the hydrophobic PCVL block mass fraction and the oil volume fraction,the formable range of the "one-step" Pickering double emulsion was determined.The increase of the PCVL block mass fraction helps to increase the proportion of the internal water phase of the Pickering double emulsion droplets and the encapsulation efficiency of vitamin B12(VB12).Based on the mechanism of the core fusion of semicrystalline PEG-b-PCVL micelles and the increase of hydrophilicity,the "one-step" Pickering double emulsion can respond rapidly in the environment of 37℃.The phenomenon of incomplete demulsification occurs,and W/O/Wtype emulsion was quickly transformed into an O/W-type emulsion,and the rapid and complete release of loaded VB12 was achieved.By combining hydrophobic PEG2k-b-PCL and PEG2k-b-PCVL block copolymer micelles as W1/O primary-emulsion emulsifiers and hydrophilic PEGsk-b-PCL micelles as doubleemulsion emulsifiers,the W1/O/W2 Pickering double emulsion with adjustable thermoresponsive properties and controlled release properties was successfully obtained by"two-step" emulsification method.The effects of secondary shearing speed and hydrophilic micelles content on the formation and properties of "two-step" Pickering double emulsions were studied.Under the condition of secondary shearing speed of 8000 rpm,the average diameter of the obtained W1/O/W2 emulsion droplets ranged from 39 μm to 106 μm by adjusting the amount of hydrophilic PEG5k-b-PCL7.8k micelles(0.01 wt%to 2 wt%).By observing the microstructure of the double emulsion after storage for 2 years,it was confirmed that the W1/O/W2 Pickering double emulsion had good physical stability at room temperature.The effect of the composition and ratio of the hydrophobic block of PEG2k-b-PCL and PEG2k-bPCVL micelles on the thermoresponsive performance and controlled release of the "two-step"double emulsion was further studied.By increasing the mole fraction of VL units in the PCVL block from 0%to 16%,the thermal response temperature of the W1/O/W2 Pickering double emulsion can be adjusted from 55℃ to 37℃.With the customizable heat-responsive phase transition behavior,the W1/O/W2 double emulsion triggers the controlled release of VB12 encapsulated in the internal water phase in different temperature environments.