Aggregation Of Amphiphilic Alginate Derivatives And Their Applation For Drug Delivery

Amphiphilic polymers that form self-assembled structures in aqueous media have been investigated and used for the diagnosis and therapy of various diseases, including cancer. In particular, some natural polymers (such as alginate, chitosan, starch and cellulose) due to its biocompatibility, low toxic, relatively low cost, and degradation.Therefore, in our work, a series of amphiphilic alginate were synthesized by efficient,andgreen chemical methods. Furthermore, its application for drug delivery and mechanism of stabilizing emulsion was invested.Firstly, a series of environment-sensitive hydrophobic alginates (Ugi-Alg) with various weight-average molecular mass values (Mw ～ 6.7×105-6.7×104g/mol) were synthesized via Ugi reaction. The structure of Ugi-Alg was characterized by 1HNMR spectrometer. The electrostatic self-assembly of different molecular weight (Mw) and composition (G/M ratio) of Ugi-Alg chain under various Na+ concentrations, was investigated by dynamic light scattering, electron spin resonance experiments, and transmission electron microscopy. Result showed that by comparing to other Ugi-Alg,the mid-Mw Ugi-Alg (Mw ～ 2.8×105g/mol) could form stable and homogeneous nanoparticles in low Na+ concentration solution. However, G/M values exerted no obvious effect on nanoparticles structure. Additionally, steady-shear flow, thixotropy and dynamical viscoelasticity tests were performed to characterize the rheological behavior of Ugi-Alg aqueous solutions as influenced by Mw and G/M ratio. All of the samples exhibited a non-Newtonian shear-thinning behavior above a critical shear rate(γc2). The greater the Mw, the more sensitive the temperature-dependent behavior will be. The upward-downward rheograms showed that all of the systems evaluated in this study displayed a hysteresis loop, indicating a strong thixotropic behavior, and the thixotropic of mid-Mw Ugi-Alg was the strongest. The dynamical viscoelastic properties were characterized by oscillatory frequency sweep, revealing the gel-like viscoelastic behavior of low-Mw and high-Mw Ugi-Alg and the fluid-like viscoelastic behavior of mid-Mw Ugi-Alg.Secondly, the effect of pH and Na+ concentration on structure and characteristics of the Ugi-Alg self-assembly micelle are studied by transmission electron microscopy and dynamic light scattering. The results indicate that the self-assembled micelle size decrease with the increasing Na+ concentration, as the pH value is contrary.Interestingly, encapsulate efficiency of acetamiprid increases due to increase in Na+concentration or decreasing pH. The release performance of the micelles is also obvious influenced by Na+ concentration and pH. The data of acetamiprid release kinetics could be well-fitted by Weibull model.Finally, alginate (Alg) is grafted onto the surface of anisotropy silica (SiO2-x)nanoparticle via Ugi reaction. The grafting is confirmed by thermal gravimetric analysis(TGA) and 1H NMR spectrometer. The data of TGA show that the degree of substitution of Alg-SiO2-x (Alg-SiO2-1, Alg-SiO2-2 and Alg-Si02-4) are 24.6%, 26.8%and 28.8%, respectively. The surface and interfacial properties of Alg-grafted-SiO2-x are characterized by dynamic light scattering and contact-angle measurement.Compared to pristine SiO2-x, modified SiO2-x possessed obvious pH-responsive properties. Stable liquid paraffin-in-water emulsions are prepared with Alg-SiO2-x. The effects of nanoparticles structure and pH value on the stability and interfacial rheological properties of emulsion are investigated by optical microscopy, multiple light scattering measurements and rheometer. It is find that, Alg-SiO2-2 has satisfying emulsification ability. Moreover, pH varied from 2.0 to 6.2, emulsion stability increases due to interaction of polymer chain lead to form three-dimensional network. When pH varied from 6.2 to 8.0, the particles charge increases so that electrostatic interaction between particles increases, emulsion stability increases. With the increasing pH to 9.0,the particles charge decreases so that emulsion stability decreases. Interestingly,usingλ-cyhalothrin as model drug,the controlled drug delivery of the emulsions as a function of pH is elucidated. The assay of controlled drug release demonstrates that with increasing pH values from 3.0 to 8.0, the cumulative release of emulsion decreases from 99.7% to 13.5%, indicating that a high triggered delivery system for pH value. The mechanism of λ-cyhalothrin release is found to vary from Fickian to complex to combined to Fickian mechanism with the increasing pH solution. This will open a new window for pH-responsive emulsion’s application to control pesticide delivery.