Chemical Papers

, Volume 72, Issue 8, pp 1869–1880 | Cite as

Tailored doxycycline delivery from MCM-41-type silica carriers

  • Mihaela Deaconu
  • Ioana Nicu
  • Robert Tincu
  • Ana-Maria Brezoiu
  • Raul-Augustin Mitran
  • Eugeniu Vasile
  • Cristian Matei
  • Daniela Berger
Original Paper


Doxycycline, an antibiotic from the tetracycline class with a broad spectrum of activity, was used to prepare drug delivery systems based on pristine and functionalized mesostructured silica supports. MCM-41-type materials with different textural, structural, and surface properties were used to assess their influence on the drug release kinetics. Small- and wide-angle XRD, FTIR spectroscopy and N2 adsorption/desorption isotherms were used to characterize the carriers before and after doxycycline loading. The drug release experiments were performed in vitro in 0.2 M phosphate buffer solution at 37 °C, and the slowest drug release kinetics was obtained for magnesium-modified MCM-41 carrier. All drug-loaded materials exhibited good antibacterial activity against Klebsiella pneumoniae ATCC 10031 strain, similar to the drug alone.


Drug delivery systems Doxycycline Mesoporous silica Release kinetics Functionalized silica 



MD is grateful to the Romanian Chemical Society for financially supporting her participation in the 20th Romanian International Conference on Chemistry and Chemical Engineering (RICCCE) 2017.


  1. Bajpai SK, Jadaun M, Bajpai M, Jyotishi P, Shah FF, Tiwari S (2017) Controlled release of doxycycline from gum acacia/poly(sodium acrylate) microparticles for oral drug delivery. Int J Biol Macromol 104:1064–1071. CrossRefGoogle Scholar
  2. Balas F, Manzano M, Horcajada P, Vallet-Regi M (2006) Confinement and controlled release of bisphosphonates on ordered mesoporous silica-based materials. J Am Chem Soc 128:8116–8117. CrossRefGoogle Scholar
  3. Beck GR Jr, Ha S-W, Camalier CE, Yamaguchi M, Li Y, Lee J-K, Weitzmann MN (2012) Bioactive silica-based nanoparticles stimulate bone-forming osteoblasts, suppress bone-resorbing osteoclasts, and enhance bone mineral density in vivo. Nanomed NBM 8:783–803. CrossRefGoogle Scholar
  4. Berger D, Nastase S, Mitran RA, Petrescu M, Vasile E, Matei C, Negreanu-Pirjol T (2016) Mesostructured silica and aluminosilicate carriers for oxytetracycline delivery systems. Int J Pharm 510:524–531. CrossRefGoogle Scholar
  5. Brentano Capeletti L, de Oliveira LF, de Almeida Goncalves K, Fernanda J, de Oliveira A, Saito A, Kobarg J, dos Santos JHZ, Cardoso MB (2014) Tailored silica-antibiotic nanoparticles: overcoming bacterial resistance with low cytotoxicity. Langmuir 30:7456–7464. CrossRefGoogle Scholar
  6. Brodersen DE, Clemons WM, Carter AP, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V (2000) The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B in the 30S ribosomal subunit. Cell 103:1143–1154. CrossRefGoogle Scholar
  7. Brunel D (1999) Functionalized micelle-templated silicas (MTS) and their use as catalysts for fine chemicals. Microporous Mesoporous Mater 27:329–344. CrossRefGoogle Scholar
  8. Cesaretti A, Carlotti B, Gentili PL, Clementi C, Germani R, Elisei F (2014) Spectroscopic investigation of the pH-controlled inclusion of doxycycline and oxytetracycline antibiotics in cationic micelles and their magnesium driven release. J Phys Chem B 118:8601–8613. CrossRefGoogle Scholar
  9. Chopra I, Roberts M (2001) Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 65:232–260. CrossRefGoogle Scholar
  10. de Oliveira Freitas LB, Corgosinho LD, Quintao Arantes Faria JA, dos Santos VM, Resende JM, Leal AS, Gomes DA, Barros de Sousa EM (2017) Multifunctional mesoporous silica nanoparticles for cancer-targeted, controlled drug delivery and imaging. Microporous Mesoporous Mater 242:271–283. CrossRefGoogle Scholar
  11. Guerra V, Silva-Cadeira PP, Terenzi H, Pereira-Maia EC (2016) Impact of metal coordination on the antibiotic and non-antibiotic activities of tetracycline-based drugs. Coord Chem Rev 327–328:188–199. CrossRefGoogle Scholar
  12. Hoffmann F, Cornelius M, Morell J, Frӧba M (2006) Silica-based mesoporous organic–inorganic hybrid materials. Angew Chem Int Ed 45:3216–3251. CrossRefGoogle Scholar
  13. Hornacek M, Hudec P, Smieskova A (2009) Synthesis and characterization of mesoporous molecular sieves. Chem Pap 63:689–697. CrossRefGoogle Scholar
  14. Ignacio M, Chubynsky MV, Slater GW (2017) Interpreting the Weibull fitting parameters for diffusion-controlled release data. Phys A 486:486–496. CrossRefGoogle Scholar
  15. Izquierdo-Barba I, Ruiz-Gonzalez L, Doadrio JC, Gonzalez-Calbet JM, Vallet-Regi M (2005) Tissue regeneration: a new property of mesoporous materials. Solid State Sci 7:983–989. CrossRefGoogle Scholar
  16. JICRA (2017) ECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-processing animals. EFSA J 15:4872. Google Scholar
  17. Koneru B, Shi Y, Wang Y-C, Chavala SH, Miller ML, Holbert B, Conson M, Ni A, Di Pasqua AJ (2015) Tetracycline-containing MCM-41 mesoporous silica nanoparticles for the treatment of Escherichia coli. Molecules 20:19690–19698. CrossRefGoogle Scholar
  18. Koninti RK, Plavai S, Satpathi S, Basu S, Hazra P (2016) Loading of an anti-cancer drug into mesoporous silica nano-channels and its subsequent release to DNA. Nanoscale 8:18436–18445. CrossRefGoogle Scholar
  19. Kopytynska-Kasperczyk A, Dobrzynski P, Pastusiak M, Jarzabek B, Prochwicz W (2015) Local delivery system of doxycycline hyclate based on ε-caprolactone copolymers for periodontitis treatment. Int J Pharm 491:335–344. CrossRefGoogle Scholar
  20. Lambs L, Brion M, Berthon G (1984) Metal ion-tetracycline interactions in biological fluids. Part 3. Formation of mixed-metal ternary complexes of tetracycline, oxytetracycline, doxycycline and minocycline with calcium and magnesium, and their involvement in the bioavailability of these antibiotics in blood plasma. Agents Actions 14:743–750. CrossRefGoogle Scholar
  21. Lambs L, Venturini M, Decock-Le Reverend B, Kozlowski H, Berthon G (1988) Metal ion-tetracycline interactions in biological fluids. Part 8. Potentiometric and spectroscopic studies on the formation of Ca(II) and Mg(II) complexes with 4-dimethylamino-tetracycline and 6-desoxy-6-demethyl-tetracycline. J Inorg Biochem 33:193–210. CrossRefGoogle Scholar
  22. Li Z, Su K, Cheng B, Deng Y (2010) Organically modified MCM-type material preparation and its usage in controlled amoxicillin delivery. J Colloid Interface Sci 342:607–613. CrossRefGoogle Scholar
  23. Liu Y, Ding X, Li J, Luo Z, Hu Y, Liu J, Dai L, Zhou J, Hou C, Cai K (2015) Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo. Nanotechnology 26:145102. CrossRefGoogle Scholar
  24. Medvecky L, Stulajterova R, Briancin J (2007) Study of controlled tetracycline release from porous calcium phosphate/polyhydroxybutyrate composites. Chem Pap 61:477–484. CrossRefGoogle Scholar
  25. Metsemakers W-J, Emanuel N, Cohen O, Reichart M, Potapova I, Schmid T, Segal D, Riool M, Kwakman PHS, de Boer L, de Breji A, Nibbering PH, Richards RG, Zaat SAJ, Moriarty TF (2015) A doxycycline-loaded polymer-lipid encapsulation matrix coating for the prevention of implant-related osteomyelitis due to doxycycline-resistant methicillin-resistant Staphylococcus aureus. J Control Release 209:47–56. CrossRefGoogle Scholar
  26. Mitran R-A, Nastase S, Matei C, Berger D (2014a) Mesostructured aluminosilicates as carriers for doxycycline-based drug delivery systems. In: 14th SGEM GeoConference on nano, bio and green-technologies for a sustainable future, SGEM2014 Conference Proceedings, SGEM2014 Conference Proceedings 1:113–120Google Scholar
  27. Mitran R-A, Nastase S, Stan C, Iorgu A, Matei C, Berger D (2014b) Doxycycline encapsulation studies into mesoporous SBA-15 silica type carriers and in vitro release. In: 14th SGEM GeoConference on nano, bio and green-technologies for a sustainable future, SGEM2014 Conference Proceedings 1:53–60Google Scholar
  28. Mitran R-A, Matei C, Berger D (2016) Correlation of mesoporous silica structural and morphological features with theoretical three-parameter model for drug release kinetics. J Phys Chem C 120:29202–29209. CrossRefGoogle Scholar
  29. Nairi V, Medda L, Monduzzi M, Salis A (2017) Adsorption and release of ampicillin antibiotic from ordered mesoporous silica. J Colloid Interface Sci 497:217–225. CrossRefGoogle Scholar
  30. Petrescu M, Mitran R-A, Luchian A-M, Matei C, Berger D (2015) Mesoporous ceria-silica composites as carriers for doxycycline. UPB Sci Bull Ser B 77:13–24Google Scholar
  31. Rakhshaei R, Namazi H (2017) A potential bioactive wound dressing based on carboxymethyl cellulose/ZnO impregnated MCM-41 nanocomposite hydrogel. Mat Sci Eng C 73:456–464. CrossRefGoogle Scholar
  32. Rimola A, Costa D, Sodupe M, Lambert J-F, Ugliengo P (2013) Silica surface features and their role in the adsorption of biomolecules: computational modeling and experiments. Chem Rev 113:4216–4313. CrossRefGoogle Scholar
  33. Shanmuganathan S, Shanumugasundaram N, Adhirajan N, Ramyaa Lakshmi TS, Babu M (2008) Preparation and characterization of chitosan microspheres for doxycycline delivery. Carbohydr Polym 73:201–211. CrossRefGoogle Scholar
  34. Siepmann J, Peppas NA (2011) Higuchi equation: derivation, applications, use and misuse. Int J Pharm 418:6–12. CrossRefGoogle Scholar
  35. Taylor KM, Kim JS, Rieter WJ, An H, Lin W, Lin W (2008) Mesoporous silica nanospheres as highly efficient MRI contrast agents. J Am Chem Soc 130:2154–2155. CrossRefGoogle Scholar
  36. Tort S, Acaturk F, Beskci A (2017) Evaluation of three-layered doxycycline-collagen loaded nanofiber wound dressing. Int J Pharm 529:642–653. CrossRefGoogle Scholar
  37. Tsou C-J, Chu C-Y, Hung Y, Mou C-Y (2013) A broad range fluorescent pH sensor based on hollow mesoporous silica nanoparticles, utilising the surface curvature effect. J Mater Chem B 1:5557–5563. CrossRefGoogle Scholar
  38. Vallet-Regi M, Ramila A, del Real RP, Perez-Pariente J (2001) A new delivery of MCM-41: drug delivery system. Chem Mater 13:308–311. CrossRefGoogle Scholar
  39. Vallet-Regi M, Balas F, Arcos D (2007) Mesoporous materials for drug delivery. Angew Chem Int Ed 46:7548–7558. CrossRefGoogle Scholar
  40. Viana RB, da Silva ABF, Pimentel AS (2012) Infrared spectroscopy of anionic, cationic, and zwitterionic surfactants. Adv Phys Chem. Google Scholar
  41. Walcarius A, Etienne M, Lebeau B (2003) Rate of access to the binding sites in organically modified silicates. 2. Ordered mesoporous silicas grafted with amine or thiol groups. Chem Mater 15:2161–2173. CrossRefGoogle Scholar
  42. Wan Y, Zhao D (2007) On the controllable soft-templating approach to mesoporous silicates. Chem Rev 107:2821–2860. CrossRefGoogle Scholar
  43. Wan MM, Sun XD, Liu S, Ma J, Zhu JH (2014) Versatile drug releaser derived from the Ti-substituted mesoporous silica SBA-15. Microporous Mesoporous Mater 199:40–49. CrossRefGoogle Scholar
  44. Wang S (2009) Ordered mesoporous materials for drug delivery. Microporous Mesoporous Mater 117:1–9. CrossRefGoogle Scholar
  45. Wang Y, Zhao Q, Han N, Bai L, Li J, Liu J, Che E, Hu L, Zhang Q, Jiang T, Wang S (2015) Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomed NBM 11:313–327. CrossRefGoogle Scholar
  46. White JP, Cantor CR (1971) Role of magnesium in the binding of tetracycline to Escherichia coli ribosomes. J Mol Biol 58:397–400. CrossRefGoogle Scholar
  47. Xu L, Zhang J, Gu H (2011) Adsorption and desorption behaviors of DNA with magnetic mesoporous silica nanoparticles. Langmuir 27:6099–6106. CrossRefGoogle Scholar
  48. Yang P, Gai S, Lin J (2012) Functionalized mesoporous materials for controlled delivery. Chem Soc Rev 41:3679–3698. CrossRefGoogle Scholar
  49. Zaidi S, Misba L, Khan AU (2017) Nano-therapeutics: a revolution in infection control in post antibiotic era. Nanomed NBM 13:2281–2301. CrossRefGoogle Scholar
  50. Zhang C, Zhou W, Liu S (2005) Synthesis and characterization of organofunctionalized MCM-41 by the original stepped template sol-gel technology. J Phys Chem B 109:24319–24325. CrossRefGoogle Scholar
  51. Zhao H, Yan W, Bian Z, Hu J, Liu H (2012) Investigation of Mg modified mesoporous silicas and their CO2 adsorption capacities. Solid State Sci 14:250–257. CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2018

Authors and Affiliations

  1. 1.Department of Inorganic Chemistry, Physical-Chemistry and ElectrochemistryUniversity “Politehnica” of BucharestBucharestRomania
  2. 2.National Institute for Chemical-Pharmaceutical Research and DevelopmentBucharestRomania
  3. 3.“Ilie Murgulescu” Institute of Physical-Chemistry, Romanian AcademyBucharestRomania
  4. 4.Department of Oxide Materials Science and EngineeringUniversity Politehnica of BucharestBucharestRomania

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