Advertisement

Toxicology of Starch-Based DDSs

  • Jin ChenEmail author
  • Ling Chen
  • Fengwei Xie
  • Xiaoxi Li
Chapter

Abstract

Because of its natural source and high biocompatibility, starch has drawn much attention in the advance of drug delivery systems (DDSs) as carrier materials. Yet, to functionalize starch to meet the material needs of smart and well-performed DDSs, starch has to be modified by numerous chemical methods, which may hamper its biocompatibility and biodegradability. Thus, it is vital to evaluate the toxicology of starch-based DDSs for its clinical application. Generally, starch-based DDSs could guarantee high biocompatibility and biodegradation. In most cases, the cellular toxicity of starch-based nanoparticulate carriers showed none or low toxicity and good compatibility with normal cells. However, in particular situations, a significant level of cytotoxicity of starch-based DDSs still exist. The toxicity of starch-based DDSs was found to be dosage-dependent, be related to the physicochemical properties such as size, charge, shape, molecular mass (M), composition, and chemical properties. Moreover, the addition of inorganic materials may bring cytotoxicity to starch-based DDSs, and its content is vital for its potential cytotoxicity. Thus, much effort is needed to create safer starch-based DDSs, despite the fact that starch still has a huge advantage over synthesized polymers in the application of drug delivery.

Keywords

Starch-based carrier material Biocompatibility Biodegradability Dosage-dependent toxicity Chemical composition Surface hydrophobicity Surface charge 

References

  1. Athira GK, Jyothi AN (2015) Cassava starch‐poly (vinyl alcohol) nanocomposites for the controlled delivery of curcumin in cancer prevention and treatment. Starch-Stärke 67:549–558CrossRefGoogle Scholar
  2. Björk E, Edman P (1990) Characterization of degradable starch microspheres as a nasal delivery system for drugs. Int J Pharm 62:187–192.  https://doi.org/10.1016/0378-5173(90)90232-SCrossRefGoogle Scholar
  3. Chen M, Gao C, Lü S, Chen Y, Liu M (2016a) Dual redox-triggered shell-sheddable micelles self-assembled from mPEGylated starch conjugates for rapid drug release. RSC Adv 6:9164–9174CrossRefGoogle Scholar
  4. Chen M, Gao C, Lü S, Chen Y, Liu M (2016b) Preparation of redox-sensitive, core-crosslinked micelles self-assembled from mPEGylated starch conjugates: remarkable extracellular stability and rapid intracellular drug release. RSC Adv 6:46159–46169CrossRefGoogle Scholar
  5. Constantin M, Fundueanu G, Cortesi R, Esposito E, Nastruzzi C (2003) Aminated polysaccharide microspheres as DNA delivery systems. Drug Delivery 10:139–149.  https://doi.org/10.1080/10717540390215537CrossRefPubMedGoogle Scholar
  6. Darroudi M, Hakimi M, Goodarzi E, Oskuee RK (2014) Superparamagnetic iron oxide nanoparticles (SPIONs): green preparation, characterization and their cytotoxicity effects. Ceram Int 40:14641–14645  https://doi.org/10.1016/j.ceramint.2014.06.051CrossRefGoogle Scholar
  7. Devy J, Balasse E, Kaplan H, Madoulet C, Andry MC (2006) Hydroxyethylstarch microcapsules: A preliminary study for tumor immunotherapy application. Int J Pharm 307:194–200.  https://doi.org/10.1016/j.ijpharm.2005.09.035CrossRefPubMedGoogle Scholar
  8. Engelberth SA, Hempel N, Bergkvist M (2015) Chemically modified dendritic starch: a novel nanomaterial for siRNA delivery. Bioconjug Chem 26:1766–1774CrossRefGoogle Scholar
  9. Fathi M, Entezami AA, Arami S, Rashidi M-R (2015) Preparation of N-isopropylacrylamide/itaconic acid magnetic nanohydrogels by modified starch as a crosslinker for anticancer drug carriers. Int J Polym Mater Polym Biomater 64:541–549  https://doi.org/10.1080/00914037.2014.996703CrossRefGoogle Scholar
  10. Huang Y, Liu M, Gao C, Yang J, Zhang X, Zhang X, Liu Z (2013) Ultra-small and innocuous cationic starch nanospheres: preparation, characterization and drug delivery study. Int J Biol Macromol 58:231–239 doi: https://doi.org/10.1016/j.ijbiomac.2013.04.006CrossRefGoogle Scholar
  11. Hubatsch I, Ragnarsson EG, Artursson P (2007) Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat Protoc 2:2111–2119CrossRefGoogle Scholar
  12. Jain R et al (2011) Enhanced cellular delivery of idarubicin by surface modification of propyl starch nanoparticles employing pteroic acid conjugated polyvinyl alcohol. Int J Pharm 420:147–155.  https://doi.org/10.1016/j.ijpharm.2011.08.030CrossRefPubMedGoogle Scholar
  13. Khan A, El-Toni AM, Alhoshan M (2012) Preparation of thermo-responsive hydrogel-coated magnetic nanoparticles. Mater Lett 89:12–15.  https://doi.org/10.1016/j.matlet.2012.08.064CrossRefGoogle Scholar
  14. Krug HF, Wick P (2011) Nanotoxicology: an interdisciplinary challenge. Angew Chem Int Ed 50:1260–1278CrossRefGoogle Scholar
  15. Kwag DS, Oh KT, Lee ES (2014) Facile synthesis of multilayered polysaccharidic vesicles. J Control Release 187:83–90.  https://doi.org/10.1016/j.jconrel.2014.05.032CrossRefPubMedGoogle Scholar
  16. Li K et al (2015) Mulberry-like dual-drug complicated nanocarriers assembled with apogossypolone amphiphilic starch micelles and doxorubicin hyaluronic acid nanoparticles for tumor combination and targeted therapy. Biomaterials 39:131–144.  https://doi.org/10.1016/j.biomaterials.2014.10.073CrossRefPubMedGoogle Scholar
  17. Likhitkar S, Bajpai AK (2014) An in vitro experimental approach to study magnetically targeted release of methotrexate from superparamagnetic starch nanocarriers. Int J Polym Mater Polymeric Biomater 63:941–950.  https://doi.org/10.1080/00914037.2014.886232CrossRefGoogle Scholar
  18. Lima-Tenório MK, Tenório-Neto ET, Guilherme MR, Garcia FP, Nakamura CV, Pineda EAG, Rubira AF (2015) Water transport properties through starch-based hydrogel nanocomposites responding to both pH and a remote magnetic field. Chem Eng J 259:620–629.  https://doi.org/10.1016/j.cej.2014.08.045CrossRefGoogle Scholar
  19. Liu K, Wang Y, Li H, Duan Y (2015) A facile one-pot synthesis of starch functionalized graphene as nano-carrier for pH sensitive and starch-mediated drug delivery. Colloids Surf B 128:86–93.  https://doi.org/10.1016/j.colsurfb.2015.02.010CrossRefGoogle Scholar
  20. Minimol PF, Paul W, Sharma CP (2013) PEGylated starch acetate nanoparticles and its potential use for oral insulin delivery. Carbohyd Polym 95:1–8.  https://doi.org/10.1016/j.carbpol.2013.02.021CrossRefGoogle Scholar
  21. Nahar K, Absar S, Patel B, Ahsan F (2014) Starch-coated magnetic liposomes as an inhalable carrier for accumulation of fasudil in the pulmonary vasculature. Int J Pharm 464:185–195.  https://doi.org/10.1016/j.ijpharm.2014.01.007CrossRefPubMedPubMedCentralGoogle Scholar
  22. Noga M et al (2013) The effect of molar mass and degree of hydroxyethylation on the controlled shielding and deshielding of hydroxyethyl starch-coated polyplexes. Biomaterials 34:2530–2538.  https://doi.org/10.1016/j.biomaterials.2012.12.025CrossRefPubMedGoogle Scholar
  23. Noga M, Edinger D, Wagner E, Winter G, Besheer A (2014) Characterization and compatibility of hydroxyethyl starch-polyethylenimine copolymers for DNA delivery. J Biomater Sci Polym Ed 25:855–871.  https://doi.org/10.1080/09205063.2014.910152CrossRefPubMedGoogle Scholar
  24. Pereira AGB, Fajardo AR, Nocchi S, Nakamura CV, Rubira AF, Muniz EC (2013) Starch-based microspheres for sustained-release of curcumin: preparation and cytotoxic effect on tumor cells. Carbohyd Polym 98:711–720.  https://doi.org/10.1016/j.carbpol.2013.06.013CrossRefGoogle Scholar
  25. Pourjavadi A, Tehrani ZM, Hosseini SH (2015) Dendritic magnetite decorated by pH-responsive PEGylated starch: a smart multifunctional nanocarrier for the triggered release of anti-cancer drugs. RSC Adv 5:48586–48595CrossRefGoogle Scholar
  26. Saikia C, Hussain A, Ramteke A, Sharma HK, Maji TK (2015) Carboxymethyl starch-chitosan-coated iron oxide magnetic nanoparticles for controlled delivery of isoniazid. J Microencapsul 32:29–39CrossRefGoogle Scholar
  27. Saikia C, Das MK, Ramteke A, Maji TK (2016) Effect of crosslinker on drug delivery properties of curcumin loaded starch coated iron oxide nanoparticles. Int J Biol Macromol 93:1121–1132.  https://doi.org/10.1016/j.ijbiomac.2016.09.043CrossRefPubMedGoogle Scholar
  28. Saikia C, Das MK, Ramteke A, Maji TK (2017) Evaluation of folic acid tagged aminated starch/ZnO coated iron oxide nanoparticles as targeted curcumin delivery system. Carbohyd Polym 157:391–399.  https://doi.org/10.1016/j.carbpol.2016.09.087CrossRefGoogle Scholar
  29. Shalviri A et al. (2012) pH-Dependent doxorubicin release from terpolymer of starch, polymethacrylic acid and polysorbate 80 nanoparticles for overcoming multi-drug resistance in human breast cancer cells. Eur J Pharm Biopharm 82:587–597  https://doi.org/10.1016/j.ejpb.2012.09.001CrossRefGoogle Scholar
  30. Thakore S, Valodkar M, Soni JY, Vyas K, Jadeja RN, Devkar RV, Rathore PS (2013) Synthesis and cytotoxicity evaluation of novel acylated starch nanoparticles. Bioorg Chem 46:26–30.  https://doi.org/10.1016/j.bioorg.2012.10.001CrossRefPubMedGoogle Scholar
  31. Thiele C, Loretz B, Lehr C-M (2017) Biodegradable starch derivatives with tunable charge density—synthesis, characterization, and transfection efficiency. Drug Deliv Transl Res 7:252–258  https://doi.org/10.1007/s13346-016-0333-8CrossRefGoogle Scholar
  32. Tuovinen L et al (2004) Starch acetate microparticles for drug delivery into retinal pigment epithelium - in vitro study. J Controlled Release 98:407–413.  https://doi.org/10.1016/j.jconrel.2004.05.016CrossRefGoogle Scholar
  33. Wang J, Liu H, Leng F, Zheng L, Yang J, Wang W, Huang CZ (2014) Autofluorescent and pH-responsive mesoporous silica for cancer-targeted and controlled drug release. Microporous Mesoporous Mater 186:187–193.  https://doi.org/10.1016/j.micromeso.2013.11.006CrossRefGoogle Scholar
  34. Xiao H, Yang T, Lin Q, Liu GQ, Zhang L, Yu F, Chen Y (2016) Acetylated starch nanocrystals: Preparation and antitumor drug delivery study. Int J Biol Macromol 89:456–464.  https://doi.org/10.1016/j.ijbiomac.2016.04.037CrossRefPubMedGoogle Scholar
  35. Xuan Phuc N et al (2012) Iron oxide-based conjugates for cancer theragnostics. Adv Nat Sci Nanosci Nanotechnol 3:033001.  https://doi.org/10.1088/2043-6262/3/3/033001CrossRefGoogle Scholar
  36. Yang Y, Jiang JS, Du B, Gan ZF, Qian M, Zhang P (2009) Preparation and properties of a novel drug delivery system with both magnetic and biomolecular targeting. J Mater Sci - Mater Med 20:301–307.  https://doi.org/10.1007/s10856-008-3577-0CrossRefPubMedGoogle Scholar
  37. Yang J, Huang Y, Gao C, Liu M, Zhang X (2014a) Fabrication and evaluation of the novel reduction-sensitive starch nanoparticles for controlled drug release. Colloids Surf B 115:368–376.  https://doi.org/10.1016/j.colsurfb.2013.12.007CrossRefGoogle Scholar
  38. Yang JL, Gao CM, Lu SY, Wang XG, Chen MJ, Liu MZ (2014b) Novel self-assembled amphiphilic mPEGylated starch-deoxycholic acid polymeric micelles with pH-response for anticancer drug delivery. RSC Adv 4:55139–55149.  https://doi.org/10.1039/c4ra07315kCrossRefGoogle Scholar
  39. Ye L et al (2016) Zwitterionic-modified starch-based stealth micelles for prolonging circulation time and reducing macrophage response. ACS Appl Mater Interfaces 8:4385–4398CrossRefGoogle Scholar
  40. Ying XY, Shan CL, Jiang KK, Chen Z, Du YZ (2014) Intracellular pH-sensitive delivery CaCO3 nanoparticles templated by hydrophobic modified starch micelles. RSC Adv 4:10841–10844  https://doi.org/10.1039/c3ra47501hCrossRefGoogle Scholar
  41. Zhang AP et al (2013) Disulfide crosslinked PEGylated starch micelles as efficient intracellular drug delivery platforms. Soft Matter 9:2224–2233.  https://doi.org/10.1039/c2sm27189cCrossRefGoogle Scholar
  42. Zohreh N, Hosseini SH, Pourjavadi A (2016) Hydrazine-modified starch coated magnetic nanoparticles as an effective pH-responsive nanocarrier for doxorubicin delivery. J Ind Eng Chem 39:203–209.  https://doi.org/10.1016/j.jiec.2016.05.029CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, School of Food Science and Engineering, Ministry of Education Engineering Research Center of Starch and Protein ProcessingSouth China University of TechnologyGuangzhouChina
  2. 2.International Institute for Nanocomposites Manufacturing (IINM), WMGUniversity of WarwickCoventryUK

Personalised recommendations