Synthesis of pH-sensitive poly(β-amino ester)-coated mesoporous silica nanoparticles for the controlled release of drugs

  • William A. Talavera-Pech
  • Adriana Esparza-Ruiz
  • Patricia Quintana-Owen
  • Alfredo R. Vilchis-Nestor
  • Jesus A. Barrón-Zambrano
  • Alejandro Ávila-Ortega
Original Article
  • 2 Downloads

Abstract

This report describes the synthesis of a controlled drug delivery system that was obtained by coating mesoporous silica nanoparticles (MSNs) with poly(β-amino ester) (PbAE), which is a solid and stable material at physiological pH, but is dissolved at acidic pH values, such as those in tumor tissues (from 5.0 to 6.5). To synthesize the system, PbAE chains were grafted onto amino-functionalized MSNs through a reaction between the surface amino groups of MSNs and the ends of acrylate chains of a PbAE. The system was physicochemically characterized by dynamic light scattering (DLS), Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, X-ray photoelectron spectrometry, and X-ray diffraction analyses. In addition, the in vitro release of doxorubicin (DOX) and doxycycline (DXY) in acidic and physiological media was evaluated. It was observed that the PbAE modification did not affect the mesoporous structure of MSNs. When the amount of 3-aminopropyltriethoxysilane was increased during functionalization, the amount of PbAE binding to MSNs increased as well. With respect to drug release, the sample with the highest amount of PbAE showed better control in the delivery of DXY and DOX in acidic media, because at pH 5.5, the release of both drugs was 40% higher than that at pH 7.4. These results reveal two aspects about the presence of PbAE in MSNs: PbAE does not affect the mesoporous structure of the nanoparticles, and PbAE is the main factor controlling the delivery of drugs in acidic media.

Keywords

Mesoporous silica nanoparticles Poly(β-amino ester) pH-sensitive Drug delivery system Doxorubicin 

Notes

Acknowledgements

This project was supported by the program of competitive funds within the 2015 FIQ-UADY call. SAXRD and XPS measurements were performed at LANNBIO Cinvestav Mérida, under support from projects FOMIX-Yucatán 2008-108160 and CONACYT LAB-2009-01 No. 123913. MSc. D. Aguilar and Ing. W. Cauich are acknowledged for their technical help.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

References

  1. Brey DM, Erickson I, Burdick JA (2008) Influence of macromer molecular weight and chemistry on poly (β-amino ester) network properties and initial cell interactions. J Biomed Mater Res, Part A 85(3):731–741CrossRefGoogle Scholar
  2. Chang B, Sha X, Guo J, Jiao Y, Wang C, Yang W (2011) Thermo and pH dual responsive, polymer shell coated, magnetic mesoporous silica nanoparticles for controlled drug release. J Mater Chem 21(25):9239–9247CrossRefGoogle Scholar
  3. Chen L, Zhang F, Wang C (2009) Rational synthesis of magnetic thermosensitive microcontainers as targeting drug carriers. Small 5(5):621–628CrossRefGoogle Scholar
  4. Chung P, Kumar R, Pruski M, Lin VS (2008) Temperature responsive solution partition of organic–inorganic hybrid poly (N-isopropylacrylamide)-coated mesoporous silica nanospheres. Adv Funct Mater 18(9):1390–1398CrossRefGoogle Scholar
  5. Coradin T, Boissière M, Livage J (2006) Sol–gel chemistry in medicinal science. Curr Med Chem 13(1):99–108CrossRefGoogle Scholar
  6. DenizáYilmaz M, FraseráStoddart J (2015) Esterase-and pH-responsive poly (β-amino ester)-capped mesoporous silica nanoparticles for drug delivery. Nanoscale 7(16):7178–7183CrossRefGoogle Scholar
  7. Du L, Liao S, Khatib HA, Stoddart JF, Zink JI (2009) Controlled-access hollow mechanized silica nanocontainers. J Am Chem Soc 131(42):15136–15142CrossRefGoogle Scholar
  8. Duivenvoorden WC, Popovic SV, Lhotak S, Seidlitz E, Hirte HW, Tozer RG et al (2002) Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer. Cancer Res 62(6):1588–1591Google Scholar
  9. Feitosa SA, Palasuk J, Kamocki K, Geraldeli S, Gregory RL, Platt JA et al (2014) Doxycycline-encapsulated nanotube-modified dentin adhesives. J Dent Res 93(12):1270–1276.  https://doi.org/10.1177/0022034514549997 CrossRefGoogle Scholar
  10. Feng W, Zhou X, He C, Qiu K, Nie W, Chen L et al (2013) Polyelectrolyte multilayer functionalized mesoporous silica nanoparticles for pH-responsive drug delivery: Layer thickness-dependent release profiles and biocompatibility. J Mater Chem B 1(43):5886–5898CrossRefGoogle Scholar
  11. Hu X, Hao X, Wu Y, Zhang J, Zhang X, Wang PC et al (2013) Multifunctional hybrid silica nanoparticles for controlled doxorubicin loading and release with thermal and pH dual response. J Mater Chem B 1(8):1109–1118CrossRefGoogle Scholar
  12. Huang IP, Sun SP, Cheng SH, Lee CH, Wu CY, Yang CS et al (2011) Enhanced chemotherapy of cancer using pH-sensitive mesoporous silica nanoparticles to antagonize P-glycoprotein-mediated drug resistance. Mol Cancer Therap 10(5):761–769.  https://doi.org/10.1158/1535-7163.mct-10-0884 CrossRefGoogle Scholar
  13. Iwasaki H, Inoue H, Mitsuke Y, Badran A, Ikegaya S, Ueda T (2002) Doxycycline induces apoptosis by way of caspase-3 activation with inhibition of matrix metalloproteinase in human T-lymphoblastic leukemia CCRF-CEM cells. J Lab Clin Med 140(6):382–386CrossRefGoogle Scholar
  14. Jakša G, Štefane B, Kovač J (2013) XPS and AFM characterization of aminosilanes with different numbers of bonding sites on a silicon wafer. Surf Interface Anal 45(11–12):1709–1713Google Scholar
  15. Kecht J, Bein T (2008) Oxidative removal of template molecules and organic functionalities in mesoporous silica nanoparticles by H2O2 treatment. Microporous Mesoporous Mater 116(1):123–130CrossRefGoogle Scholar
  16. Kecht J, Schlossbauer A, Bein T (2008) Selective functionalization of the outer and inner surfaces in mesoporous silica nanoparticles. Chem Mater 20(23):7207–7214CrossRefGoogle Scholar
  17. Kim Y, Zhang C, Cho C, Cho M, Jiang H (2013) Poly (amino ester)s-based polymeric gene carriers in cancer gene therapy. In: Wei M, Good D (eds) Novel gene therapy approaches.  https://doi.org/10.5772/54740
  18. Kleitz F, Schmidt W, Schüth F (2003) Calcination behavior of different surfactant-templated mesostructured silica materials. Microporous Mesoporous Mater 65(1):1–29CrossRefGoogle Scholar
  19. Lee C, Cheng S, Huang I, Souris JS, Yang C, Mou C et al (2010) Intracellular pH-responsive mesoporous silica nanoparticles for the controlled release of anticancer chemotherapeutics. Angew Chem 122(44):8390–8395CrossRefGoogle Scholar
  20. Lin Y, Wallace G (1994) Factors influencing electrochemical release of 2, 6-anthraquinone disulphonic acid from polypyrrole. J Control Release 30(2):137–142CrossRefGoogle Scholar
  21. Lynn DM, Amiji MM, Langer R (2001) pH-responsive polymer microspheres: Rapid release of encapsulated material within the range of intracellular pH. Angew Chem Int Ed 40(9):1707–1710CrossRefGoogle Scholar
  22. Meng H, Liong M, Xia T, Li Z, Ji Z, Zink JI et al (2010a) Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line. ACS Nano 4(8):4539–4550CrossRefGoogle Scholar
  23. Meng H, Xue M, Xia T, Zhao Y, Tamanoi F, Stoddart JF et al (2010b) Autonomous in vitro anticancer drug release from mesoporous silica nanoparticles by pH-sensitive nanovalves. J Am Chem Soc 132(36):12690–12697CrossRefGoogle Scholar
  24. Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12(11):991CrossRefGoogle Scholar
  25. Na K (2007) pH-sensitive polymeric micelles for the effective delivery of anti-cancer drug. Korean J Gastroenterol Taehan Sohwagi Hakhoe Chi 49(5):314–319Google Scholar
  26. Naruphontjirakul P, Viravaidya-Pasuwat K (2011) Development of doxorubicin—core–shell chitosan nanoparticles to treat cancer. In: Paper presented at the proceedings of the international conference on biomedical engineering and technology, IACSIT Press, Singapore, vol 11, pp 90–94Google Scholar
  27. Pang J, Luan Y, Li F, Cai X, Du J, Li Z (2011) Ibuprofen-loaded poly(lactic-co-glycolic acid) films for controlled drug release. Int J Nanomed 6:659–665.  https://doi.org/10.2147/ijn.s17011 CrossRefGoogle Scholar
  28. Peng C, Zhao Q, Gao C (2010) Sustained delivery of doxorubicin by porous CaCO3 and chitosan/alginate multilayers-coated CaCO3 microparticles. Colloid Surf A Physicochem Eng Aspects 353(2):132–139CrossRefGoogle Scholar
  29. Petrescu M, Mitran RA, Luchian AM, Matei C, Berger D (2015) Mesoporous ceria-silica composites as carriers for doxycycline. UPB Sci Bull Ser B: Chem Mater Sci 77(3):13–24Google Scholar
  30. Potineni A, Lynn DM, Langer R, Amiji MM (2003) Poly (ethylene oxide)-modified poly (β-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery. J Control Release 86(2):223–234CrossRefGoogle Scholar
  31. Radu DR, Lai C, Wiench JW, Pruski M, Lin VS (2004) Gatekeeping layer effect: A poly (lactic acid)-coated mesoporous silica nanosphere-based fluorescence probe for detection of amino-containing neurotransmitters. J Am Chem Soc 126(6):1640–1641CrossRefGoogle Scholar
  32. Roberts JR, Ritter DW, McShane MJ (2013) A design full of holes: Functional nanofilm-coated microdomains in alginate hydrogels. J Mater Chem B 1(25):3195–3201CrossRefGoogle Scholar
  33. Rosenholm JM, Meinander A, Peuhu E, Niemi R, Eriksson JE, Sahlgren C et al (2008) Targeting of porous hybrid silica nanoparticles to cancer cells. ACS Nano 3(1):197–206CrossRefGoogle Scholar
  34. Rosenholm JM, Sahlgren C, Lindén M (2010) Towards multifunctional, targeted drug delivery systems using mesoporous silica nanoparticles–opportunities and challenges. Nanoscale 2(10):1870–1883CrossRefGoogle Scholar
  35. Shen Y, Tang H, Zhan Y, Van Kirk EA, Murdoch WJ (2009) Degradable poly (β-amino ester) nanoparticles for cancer cytoplasmic drug delivery. Nanomed Nanotechnol Biol Med 5(2):192–201CrossRefGoogle Scholar
  36. Siepmann J, Siepmann F (2008) Mathematical modeling of drug delivery. Int J Pharm 364(2):328–343CrossRefGoogle Scholar
  37. Silvestri B, Guarnieri D, Luciani G, Costantini A, Netti P, Branda F (2012) Fluorescent (rhodamine), folate decorated and doxorubicin charged, PEGylated nanoparticles synthesis. J Mater Sci Mater Med 23(7):1697–1704CrossRefGoogle Scholar
  38. Stuart BH (2004) Organic molecules. I: David JA, Dartford K (ed), Infrared spectroscopy: Fundamentals and applications (pp. 71–80, 83). John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, WileyGoogle Scholar
  39. Talavera-Pech WA, Esparza-Ruiz A, Quintana-Owen P, Vilchis-Nestor AR, Carrera-Figueiras C, Ávila-Ortega A (2016) Effects of different amounts of APTES on physicochemical and structural properties of amino-functionalized MCM-41-MSNs. J Sol-Gel Sci Technol 80(3):697–708CrossRefGoogle Scholar
  40. Talelli M, Iman M, Varkouhi AK, Rijcken CJ, Schiffelers RM, Etrych T et al (2010) Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin. Biomaterials 31(30):7797–7804CrossRefGoogle Scholar
  41. Tang H, Guo J, Sun Y, Chang B, Ren Q, Yang W (2011) Facile synthesis of pH sensitive polymer-coated mesoporous silica nanoparticles and their application in drug delivery. Int J Pharm 421(2):388–396CrossRefGoogle Scholar
  42. Tang S, Yin Q, Zhang Z, Gu W, Chen L, Yu H et al (2014) Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer. Biomaterials 35(23):6047–6059CrossRefGoogle Scholar
  43. Van Speybroeck M, Barillaro V, Thi TD, Mellaerts R, Martens J, Van Humbeeck J et al (2009) Ordered mesoporous silica material SBA-15: A broad-spectrum formulation platform for poorly soluble drugs. J Pharm Sci 98(8):2648–2658CrossRefGoogle Scholar
  44. Victor SP, Kumar TS (2008) BCP ceramic microspheres as drug delivery carriers: synthesis, characterisation and doxycycline release. J Mater Sci Mater Med 19(1):283–290CrossRefGoogle Scholar
  45. Wallace SJ, Li J, Nation RL, Boyd BJ (2012) Drug release from nanomedicines: Selection of appropriate encapsulation and release methodology. Drug Deliv Transl Res 2(4):284–292CrossRefGoogle Scholar
  46. Wang C, Whitten PG, Too CO, Wallace GG (2008) A galvanic cell driven controlled release system based on conducting polymers. Sens Actuators B Chem 129(2):605–611CrossRefGoogle Scholar
  47. Yang Y, Yan X, Cui Y, He Q, Li D, Wang A et al (2008) Preparation of polymer-coated mesoporous silica nanoparticles used for cellular imaging by a “graft-from” method. J Mater Chem 18(47):5731–5737CrossRefGoogle Scholar
  48. Yang P, Gai S, Lin J (2012) Functionalized mesoporous silica materials for controlled drug delivery. Chem Soc Rev 41(9):3679–3698CrossRefGoogle Scholar
  49. Yang K, Zhang C, Wang W, Wang PC, Zhou J, Liang X (2014) pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment. Cancer Biol Med 11(1):34Google Scholar
  50. Zhu Y, Shi J (2007) A mesoporous core-shell structure for pH-controlled storage and release of water-soluble drug. Microporous Mesoporous Mater 103(1):243–249CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • William A. Talavera-Pech
    • 1
  • Adriana Esparza-Ruiz
    • 2
  • Patricia Quintana-Owen
    • 3
  • Alfredo R. Vilchis-Nestor
    • 4
  • Jesus A. Barrón-Zambrano
    • 2
  • Alejandro Ávila-Ortega
    • 2
  1. 1.Centro de Investigación en CorrosiónUniversidad Autónoma de CampecheSan Francisco de CampecheMéxico
  2. 2.Faculty of Chemical EngineeringUniversidad Autónoma de Yucatán (UADY)MéridaMéxico
  3. 3.Centro de Investigación y de Estudios Avanzados, Unidad MéridaMéridaMéxico
  4. 4.Centro Conjunto de Investigación en Química Sustentable, UAEM-UNAMTolucaMéxico

Personalised recommendations