| Starch nanoparticles are 1–1000 nm in the pharmaceutical field and feature biodegradability,reproducibility and cheapness as potential drug carriers.Currently,water-in-oil miniemulsion technology is the most commonly employed to produce various starch nanoparticles.However,most of the particles obtained by these techniques yield a correspondingly large particle size of up to 1?m.Therefore,how to reduce the particle size of emulsion droplets to nano-scale droplets has become a technical difficulty in the preparation of starch nanoparticles.Starch nanoparticles can be used as potential drug carriers,especially for colon-specific drug delivery.Retrograded starch?RS3?and chemically modified starch?RS4?plays a vital role in digestive physiology as a functional dietary fiber,which can avoid degradation before it reaches the colon.However,RS3 and RS4 in the colon can be fermented by colonic bacteria.Considering these characteristics,RS3 and RS4 can be used as potential drug carriers for colon-specific drug delivery.Nevertheless,native RS3 and RS4 is characterized by several limitations due to its big particle size and low surface/volume ratio,which restrict their industrial applications.Therefore,RS3 and RS4 needs to be modified through nanotechnology to improve their properties.Based on the above-mentioned facts,the specific objectives of this study are as follows:?1?to investigate new synthesis routes of producing RS3 and RS4nanoparticles basing on water-in-oil?w/o?miniemulsion cross-linking;?2?to study the effect of drying methods including heated-air drying,vacuum freeze drying,and spray drying on the RS3 and RS4 nanoparticles prepared ultrasonication and miniemulsion cross-linking,homogenization and miniemulsion cross-linking,and high-speed shearing and miniemulsion cross-linking;and?3?to examine the effects of nanosizing on the physicochemical and functional properties of RS3 and RS4 nanoparticles were also investigated.The main findings are as follows:?1?Optimization of RS3 and RS4 nanoparticles through ultrasonication and miniemulsion cross-linkingA four-factor Box–Behnken design and optimization was used to minimize particle size through the developed nanoscale RS3 based on 29 different experimental data obtained in a batch study.Four independent variables,namely,ultrasonic power?100–300 W?,sonication time?40–120 min?,starch content?0.5–1.5 g/100mL?,and oil/water ratio?6:1–10:1?,were transformed to coded values,and a quadratic model was established to predict the responses.Variable optimization for minimizing particle size by high-power ultrasonication was performed using the quadratic model.The predicted minimized particle average size?611.7 nm?under the optimum conditions of the process variables?ultrasonic power,231.5 W;sonication time,85.2 min;starch content,1.1g/100mL;and oil/water ratio,10:1?was very close to the experimental value?606.2 nm?determined in the batch experiment.A three-factor Box–Behnken design and optimization was used to minimize particle size through the developed RS4 nanoparticles.Three independent variables,namely,ultrasonic power?100–300 W?,sonication time?80–160 min?,and oil/water ratio?8:1–12:1?,were transformed to coded values,and a quadratic model was established to predict the responses.The predicted minimized particle average size?576.1 nm?under the optimum conditions of the process variables?ultrasonic power,214.6 W;sonication time,114.7 min;and oil/water ratio,10.5:1?was very close to the experimental value?591.0 nm?determined in a batch experiment.In summary,ultrasonication and miniemulsion cross-linking could produce nanoscale starch,but the particle size was still large.?2?Optimization of RS3 and RS4 nanoparticles through homogenization and miniemulsion cross-linkingA new and convenient route to synthesizing RS3 and RS4 nanoparticles through homogenization combined with a water-in-oil miniemulsion cross-linking technique was developed.RS3 and RS4 nanoparticles were optimized with regard to particle average size by using three-factor-three-level Box–Behnken design.Homogenization pressure,oil/water ratio,and surfactant were selected as independent variables,whereas particle size was considered as a dependent variable.Results indicated that homogenization pressure was the main contributing variable for particle size.The optimum values of RS3 nanoparticles for homogenization pressure,oil/water ratio,and surfactant were 30 MPa,9.3:1,and 25.4 g,respectively,whereas the particle size was predicted to be 228.2 nm.Moreover,the following optimum preparation conditions were obtained to achieve the minimum average size of RS4 nanoparticles:50 MPa homogenization pressure,9.7:1 oil/water ratio,and 17.8 g surfactant amount,when the predicted particle average size was 303.6 nm.Results indicated that the particle size of RS3 and RS4 nanoparticles prepared by homogenization and miniemulsion cross-linking was smaller than the particle size of RS3 and RS4 nanoparticles prepared by ultrasonication and miniemulsion cross-linking.?3?Optimization of RS3 and RS4 nanoparticles through high-speed shearing and miniemulsion cross-linkingRS3 and RS4 nanoparticles were synthesized via a novel preparation route through high-speed shearing emulintestinal juicesication.The effects of the shear rate,shear time,oil/water ratio,and surfactant on the average size of RS3 and RS4 nanoparticles were investigated by using Box–Behnken experimental design.Under the optimal conditions,i.e.,27915 rpm shear rate,10.9 min shear time,9.8:1 oil/water ratio,and33.7 g surfactant,the minimum average size?273.0 nm?of RS III nanoparticles were successfully obtained.In additional,under the optimal conditions,i.e.,25798 rpm shear rate,9.8 min shear time,10:1 oil/water ratio,and 18.2 g surfactant,the minimum average size?311.5 nm?of RS4 nanoparticles were successfully obtained.Results indicated that high-speed shearing and miniemulsion cross-linking could produce RS3and RS4 nanoparticles.?4?Effect of drying methods including heated-air drying,vacuum freeze drying,and spray drying on the RS3 and RS4 nanoparticles prepared by ultrasonication and miniemulsion cross-linking,homogenization and miniemulsion cross-linking,and high-speed shearing and miniemulsion cross-linking.Results showed that there was no significant difference between the RS3 and RS4nanoparticles of hot air drying and vacuum freeze drying in the yield?p<0.05?,which were significantly higher than those of spray dried RS3 and RS4 nanoparticles?p<0.05?.And there was no difference in brightness between the RS3 and RS4nanoparticles of the vacuum freeze drying and the spray drying?p<0.05?,which were better than the brightness of the hot air dried RS3 and RS4 nanoparticles?p<0.05?.Moreover,the particle size of vacuum freeze dried RS3 and RS4 nanoparticles was lower than that of spray dried RS3 and RS4 nanoparticles,but there was no significant difference among them?p<0.05?,and both were significantly lower than those of hot air dried RS3 and RS4 nanoparticles?p<0.05?.In additional,the absolute value of zeta potential in the vacuum freeze dried RS3 and RS4 nanoparticles was higher than those of spray dried and hot air dried RS3 and RS4 nanoparticles?p<0.05?.The cyclohexane residues can not be tested in spray dried and hot air dried RS3 and RS4 nanoparticles.And the cyclohexane residues can be tested in vacuum freeze dried RS3 and RS4nanoparticles,but they did not exceed the PED value of cyclohexane.?5?The structural properties of the RS3 and RS4 nanoparticles prepared by ultrasonication and miniemulsion cross-linking,homogenization and miniemulsion cross-linking,and high-speed shearing and miniemulsion cross-linking,such as their average particle size,morphology,specific surface area and pore size distribution,polarized light microscopy,crystal structure,functional group and average degree of polymerization,were the assessed.Dynamic light scattering experiments revealed that RS3 and RS4 nanoparticles measuring PdIs lower than 0.5 and particle average sizes were approximately nanoscale.Scanning electron microscopy observation revealed that the surface of RS3 and RS4nanoparticles appeared to be progressively broken down and eroded,and the agglomeration structure was formed.BET results showed that RS3 and RS4nanoparticles had mesoporous pores with significantly higher surface area than RS3 and RS4,which was about 1014 times of the RS3 and RS4.X-ray diffraction analysis indicated that nanosizing destroyed the crystalline structure of the clustered amylopectin and apparently led to amorphous or low-crystallinity RS3 and RS4 nanoparticles.Fourier transform infrared spectra showed two new peaks about 1500 and 1400 cm-1,and the new peak at 1500 cm-11 can be considered the most satisfying evidence of the crosslinking reaction between starch molecule and N,N-methylene diacrylamid.Raman confirmed the result of FTIR that starch molecule crosslinked with N,N-methylene diacrylamid.And the average degree of polymerization of RS3 and RS4 nanoparticles was lower than RS3 and RS4.?6?The physicochemical properties of RS3 and RS4 nanoparticles prepared by ultrasonication and miniemulsion cross-linking,homogenization and miniemulsion cross-linking,and high-speed shearing and miniemulsion cross-linking were also determined.As compared with RS3 and RS4,the absolute value of zeta potential of RS3 and RS4 nanoparticles was higher,and the amylose content,solubility,and swelling power increased,but luminosity and resistant starch content decreased.In vitro digestibility results suggested that these nanoparticles exhibited high resistance to digestion in stomach,small intestine and colon contents of mouse.Differential scanning calorimetry results showed that RS3 and RS4 nanoparticles exhibited lower Tc-To and?H values.And these nanoparticles were found to be most stable in increased pH or decreased NaCl concentration with good thermal and storage stabilities.?7?Drug-absorption and in vitro release properties of RS3 and RS4 nanoparticles prepared ultrasonication and miniemulsion cross-linking,homogenization and miniemulsion cross-linking,and high-speed shearing and miniemulsion cross-linking were discussedThe absorption properties of RS3 and RS4 nanoparticles improved when compared with RS3 and RS4,and the adsorption kinetic described the contact time on the adsorption of captopril onto RS3 and RS4 nanoparticles.The intraparticle diffusion model commonly divides the adsorption process into three stages:?1?the transport of captopril from solution to the surface of RS3 and RS4 nanoparticles,which is the rapid surface adsorption stage,?2?the gradual inward diffusion stage,and?3?the final equilibrium stage.In vitro release experiment of RS3 and RS4 nanoparticles indicated that the drug was released as follows:lower 30%after 2 h in SGF,lower 50%after 6 h in SIF,and higher 90%after 12 h in SCF.In conclusion,three new and convenient synthesis routes by using ultrasonication,homogenization,high-speed shearing combined with water-in-oil miniemulsion cross-linking technique were used to prepare RS3 and RS4 nanoparticles,respectively.Moreover,the physicochemical properties of RS3 and RS4 nanoparticles were strictly dependent on the process applied during preparation process.Undoubtedly,the differences in structural properties were associated with better functional properties of RS3 and RS4 nanoparticles. |
PDF Full Text Request