Elsevier

Carbohydrate Polymers

Volume 176, 15 November 2017, Pages 203-213
Carbohydrate Polymers

A pH-responsive emulsion stabilized by alginate-grafted anisotropic silica and its application in the controlled release of λ-cyhalothrin

https://doi.org/10.1016/j.carbpol.2017.07.046Get rights and content

Highlights

  • Alg-SiO2-x samples were synthesized via the Ugi reaction.

  • Compared with pristine SiO2-x, modified SiO2-x possessed obvious pH-responsive properties.

  • Stable liquid paraffin-in-water emulsions were prepared with Alg-SiO2-x.

  • The results of sustained-release assay demonstrated that the emulsion is a pH-responsive drug delivery system.

  • The sustained-release curves of λ-cyhalothrin are describable by the Weibull model.

Abstract

Alginate (Alg) was grafted on the surface of anisotropic silica (SiO2-x) via the Ugi reaction (Alg-SiO2-1, Alg-SiO2-2, and Alg-SiO2-4). Compared with pristine SiO2-x, modified SiO2-x is more sensitive to pH. Three stable liquid paraffin-in-water emulsions were prepared with Alg-SiO2-1, Alg-SiO2-2, and Alg-SiO2-4. Alg-SiO2-2 exhibited satisfactory emulsification ability. The emulsions became more stable as emulsion pH varied from 2.0 to 6.2 because of polymer chain interactions that led to the formation of a three-dimensional network. When the emulsion pH varied from 6.2 to 8.0, the particle charge increased, in turn increasing interparticle the electrostatic interactions that increased emulsion stability. When the emulsion pH was 9.0, the subsequent decrease in particle charge, decreased the emulsion stability. The model drug λ-cyhalothrin was embedded in the emulsions. A sustained-release assay demonstrated that increasing emulsion pH from 3.0 to 8.0 decreased cumulative drug release from the emulsion from 99.7% to 13.5%. This result indicated that the emulsion is a pH triggered drug delivery system. The sustained-release curves of λ-cyhalothrin are describable by the Weibull model.

Introduction

In recent years, environmentally responsive “intelligent” materials, such as those that are responsive to pH (Sonawane, Kalhapure, & Govender, 2017), temperature (Huo, Ma, Dong, & Qu, 2017), redox (Chen, Dong, Qi, Song, & Sun, 2017; Chen, Sun et al., 2017), magnetism (Mansouri, Nazarpak, Solouk, Akbari, & Hasani-Sadrabadi, 2017), ultrasound (Leong, Martin, & Ashokkumar, 2017), and ionic strength (Zhang et al., 2015), have attracted considerable interest as controlled release systems for drug delivery. These materials can maintain a drug in its desired therapeutic range with a single dose and localize drug delivery to a particular part of the body. These properties decrease the systemic drug level, reduce the need for follow-up care, preserve medications that are rapidly destroyed in the body, and increase patient comfort and/or improve compliance (Esser-Kahn, Odom, Sottos, White, & Moore, 2011; Kost & Langer, 2012).

Pesticides are indispensable in modern agriculture. However, the utilization rate of conventional pesticides is only 10%. Given the limitations of environmental conditions and mode of application, 90% of applied conventional pesticides never reach their target to induce the desired biological response at the precise times and quantities required thus causing waste and considerable damage to the environment (Yi et al., 2011). Therefore, the application of environmentally responsive “intelligent” materials in pesticides delivery is an important research topic in the development of new pesticide formulations. For instance, Chen et al. (2016) prepared copper (II) Schiff base mesoporous silica (Cu-MCM-41) via co-condensation; chlorpyrifos was then supported on Cu-MCM-41 to form a highly efficient pH-responsive sustained-release system for pesticide delivery.

Pickering emulsions are stabilized by rigid inorganic particles (e.g., silica nanoparticles) and soft polymer particles with good surface wettability. Stable Pickering emulsions are widely used in foods (Eslami, Davarpanah, & Vahabzadeh, 2017), cosmetics (Marto et al., 2016), medicines (Marto et al., 2015; Shah, Zhang, Li, & Li, 2016), and pesticides (Fang, Yang, Gao, & Li, 2015), as well as in emulsion polymerization (Zhu, Jiang, Sun, Yana, & Li, 2016), oil recovery (AfzaliTabar, Alaei, Khojasteha, Motieea, & Rashidi, 2017), and nanoparticle synthesis (Zenerino, Peyratout, & Aimable, 2015). The strong shielding effects imparted by solid particles, however, have restricted the use of Pickering emulsions in applications that requires temporal stabilization and subsequent demulsification. Therefore, pH-responsive emulsions have been extensively studied given their ability to transform between stable and unstable forms through pH stimulation (Tu & Lee, 2014).

Silica nanoparticles are potential candidates for stabilizing emulsions and sustained-release applications due to their unique features, including: (i) morphological control; (ii) excellent chemical and thermal stability, as well as dispersibility in aqueous media; (iii) diffusional barrier; (iv) biocompatibility the U.S. Food and Drug Administration considers silica as generally recognized as safe; and (v) tunable physical and chemical surface properties (Chen et al., 2016). However, pure silica particles are highly hydrophilic and may not be able to stabilize emulsions. In addition, the silica surface does not exhibit significant pH sensitivity given its absence of carboxyl or amino groups. Therefore, the modification of silica via physical adsorption or grafting, such as post-synthetic grafting and co-condensation, has received considerable attention (Wibowo, Hui, Middelberg, & Zhao, 2016).

Alginate (Alg) is a low-toxicity, biocompatible, inexpensive, biodegradable material that exhibits mild gelation with the addition of divalent cations, such as Ca2+ (Lee & Mooney, 2012). It has been extensively investigated in the food industry, environmental engineering, pharmaceuticals, regenerative medicine, and chemical engineering (Bastakoti, Liao et al., 2013; Bastakoti, Hsu et al., 2013; Li, Liu, Huang, & Xue, 2011; Liao et al., 2015). The good pH sensitivity of alginate results from the numerous free carboxyl groups along its backbone. Hsu, Yu, and Huang (2013) designed and fabricated pH-responsive calcium pectinate/alginate microspheres to exploit their pH-sensitive properties for the colon-targeted delivery of encapsulated cisplatin. A sustained-release assay demonstrated that the release of cisplatin was more sustained in simulated gastric fluid than in simulated intestinal fluid, due to the increased solubility of the coating polymer in media with pH >7.0.

In this work, Alg was grafted onto the surface of anisotropic silica (SiO2-x) nanoparticles via the Ugi reaction without the aid of a catalyst with an inherently high atomic economy and chemical yield. pH-responsive emulsions was prepared using the modified SiO2-x nanoparticles (Alg-SiO2-x). The effects of nanoparticle structure and pH on the stability, and rheological properties of the emulsions were investigated via optical microscopy, multiple light scattering measurements, and rheometer. In addition, the controlled drug delivery of the emulsions as a function of pH was elucidated using λ-cyhalothrin as model drug. This study provides a new approach to the application of pH-responsive emulsions in controlled pesticide delivery systems.

Section snippets

Materials

3-Aminopropyltriethoxysilane(APTS), paraffin liquid, glutaraldehyde(GA), formaldehyde, octylamine, hydrochloric acid, sodium hydroxide, and ethanol were used as received from Aladdin Chemical Reagent Co., Ltd. (Shanghai, China). Alg with molecular masses of Mw = 273.645 and Mn = 181.642 was purchased from the J & K Technology Co., Ltd. (Beijing, China). As determined via circular dichroism, the ratio of guluronic acid to mannuronic acid was 1.32. Cyclohexyl isocyanide was purchased from J & K

Characterization of Alg-SiO2-x

Alg-SiO2-x was synthesized via a four-component Ugi reaction, as shown in Scheme 1. In this reaction, an imine was first formed by mixing formaldehyde with amine-capped silica and one equivalent of water was lost. An imine with cyclohexyl isocyanide and alginate acid generated the intermediate with the aid of nucleophilic addition. Finally, Mumm rearrangement occursed through acyl transfer to the bis-amide; this reaction is irreversible and drives the entire reaction without catalysis. The Ugi

Conclusion

pH-responsive Alg-SiO2-x were synthesized via the Ugi reaction without the aid of a catalyst and with an inherently high atomic economy and chemical yield. Grafting was confirmed via 1H NMR. The TGA data showed DS of 24.6%, 26.8% and 28.8% for Alg-SiO2-x (Alg-SiO2-1, Alg-SiO2-2 and Alg-SiO2-4), respectively. The data of DLS, TEM, and contact-angle measurement indicated that the modified nanoparticles displayed significant surface and interfacial properties when the carboxyl groups on Alg were

Conflicts of interest

The authors declare no competing financial interest.

Acknowledgements

We gratefully acknowledge the financially supported from the National Natural Science Foundation of China (21366010, 21566009 and 31360432), the Natural Science Foundation of Hainan Province (217021, 20162013 and 20162016), and the financial support from the Key Projects in the Hainan provincial Science & Technology Program (cxy20150026).

References (53)

  • D. Kpogbemabou et al.

    Oil-in-water Pickering emulsions stabilized by phyllosilicates at high solid content

    Colloids and Surfaces A—Physicochemical and Engineering Aspects

    (2014)
  • K.Y. Lee et al.

    Alginate: properties and biomedical applications

    Progress in Polymer Science

    (2012)
  • T.S.H. Leong et al.

    Ultrasonic encapsulation—A review

    Ultrasonics Sonochemistry

    (2017)
  • J. Lu et al.

    A pH responsive Pickering emulsion stabilized by fibrous palygorskite particles

    Applied Clay Science

    (2014)
  • J. Ma et al.

    Flow behavior, thixotropy and dynamical viscoelasticity of sodium alginate aqueous solutions

    Food Hydrocolloids

    (2014)
  • M. Mansouri et al.

    Magnetic responsive of paclitaxel delivery system based on SPION and palmitoyl chitosan

    Journal of Magnetism and Magnetic Materials

    (2017)
  • J. Marto et al.

    Starch-based Pickering emulsions for topical drug delivery: A QbD approach

    Colloids and Surfaces B: Biointerfaces

    (2015)
  • J. Marto et al.

    Design of novel starch-based Pickering emulsions as platforms for skin photoprotection

    Journal of Photochemistry & Photobiology, B: Biology

    (2016)
  • V. Papadopoulou et al.

    On the use of the Weibull function for the discernment of drug release mechanisms

    International Jouranal of Pharmaceutics

    (2006)
  • B.R. Shah et al.

    Bioaccessibility and antioxidant activity of curcumin after encapsulated by nano and Pickering emulsion based on chitosan-tripolyphosphate nanoparticles

    Food Research International

    (2016)
  • B. Shi et al.

    Aminopropyl-functionalized silicas synthesized by W/O microemulsion for immobilization of penicillin G acylase

    Catalysis Today

    (2009)
  • S.J. Sonawane et al.

    Hydrazone linkages in pH responsive drug delivery systems

    European Journal of Pharmaceutical Sciences

    (2017)
  • X. Song et al.

    Preparation and characterizations of Pickering emulsions stabilized by hydrophobic starch particles

    Food Hydrocolloids

    (2015)
  • Y. Tan et al.

    Triglyceride-water emulsions stabilised by starchebased nanoparticles

    Food Hydrocolloids

    (2014)
  • Z.H. Tian et al.

    Rheological properties of glutaraldehyde-crosslinked collagen solutions analyzed quantitatively using mechanical models

    Materials Science and Engineering: C

    (2016)
  • F. Wang et al.

    Self-assembly of novel tris(p-carboxyphenyl) porphyrin monomer and its copolymers with acrylamide in aqueous media

    Dyes and Pigments

    (2011)
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      It has received extensive attention in the field of drug sustained release in recent years. The grafting of alginate (Alg) onto the silica surface via Ugi reaction makes the modified silica more sensitive to pH. By increasing the pH from 3 to 8, the release of loaded pesticide (λ-cyhalothrin) in the alginate@silica carrier in 25 % methanol solution decreased from 99.7 % to 13.5 % in 800 min [76]. In addition, mesoporous silica nanoparticles (MSNs) are also good carriers for agrochemicals.

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