Fabrication and characterisation studies of cyclodextrin-based nanosponges for sulfamethoxazole delivery

Abstract

β-Cyclodextrin based nanosponges have been synthesized in three molar ratios, and characterized by phase solubility studies, Fourier-transform infrared spectroscopy, matrix-assisted laser desorption/ionization time of flight mass spectrometry, and scanning electron microscopy. Following characterization studies, a model anti-bacterial agent, sulfamethoxazole, has been loaded within the nanosponges, and in vitro drug release studies were carried out. According to results, nanosponges below  ~ 100 nm diameter were obtained with a characteristic sponge-like morphology. Phase solubility studies demonstrated that β-cyclodextrin nanosponges improve solubility of the drug up to 30-fold. These results suggest that nanosponges could improve the bioavailability of drugs by conducing them to reach desired plasma concentrations for therapeutic effect.

Graphic abstract

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

References

  1. 1.

    Li, B., Webster, T.J.: Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections. J. Orthop. Res. 36(1), 22–32 (2018). https://doi.org/10.1002/jor.23656

    Article  PubMed  Google Scholar 

  2. 2.

    Kollef, M.H., Sherman, G., Ward, S., Fraser, V.J.: Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 115(2), 462–474 (1999). https://doi.org/10.1378/chest.115.2.462

    Article  PubMed  CAS  Google Scholar 

  3. 3.

    Mathews, C.J., Weston, V.C., Jones, A., Field, M., Coakley, G.: Bacterial septic arthritis in adults. Lancet 375(9717), 846–855 (2010). https://doi.org/10.1016/S0140-6736(09)61595-6

    Article  PubMed  Google Scholar 

  4. 4.

    Nair, R., Schweizer, M.L., Singh, N.: Septic arthritis and prosthetic joint infections in older adults. Infect. Dis. Clin. North Am. 31(4), 715–729 (2017). https://doi.org/10.1016/j.idc.2017.07.013

    Article  PubMed  Google Scholar 

  5. 5.

    Challa, R., Ahuja, A., Ali, J., Khar, R.: Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech 6(2), E329–E357 (2005)

    Article  Google Scholar 

  6. 6.

    Del Valle, E.M.: Cyclodextrins and their uses: a review. Process Biochem. 39(9), 1033–1046 (2004)

    Article  CAS  Google Scholar 

  7. 7.

    Brewster, M.E., Loftsson, T.: Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Del. Rev. 59(7), 645–666 (2007)

    Article  CAS  Google Scholar 

  8. 8.

    Saokham, P., Muankaew, C., Jansook, P., Loftsson, T.: Solubility of cyclodextrins and drug/cyclodextrin complexes. Molecules 23(5), 1161 (2018)

    Article  CAS  Google Scholar 

  9. 9.

    Pavlov, G.M., Korneeva, E.V., Smolina, N.A., Schubert, U.S.: Hydrodynamic properties of cyclodextrin molecules in dilute solutions. Eur. Biophys. J. 39(3), 371–379 (2010)

    Article  CAS  Google Scholar 

  10. 10.

    Sherje, A.P., Dravyakar, B.R., Kadam, D., Jadhav, M.: Cyclodextrin-based nanosponges: a critical review. Carbohydr. Polym. 173, 37–49 (2017)

    Article  CAS  Google Scholar 

  11. 11.

    Loftsson, T., Jarho, P., Masson, M., Järvinen, T.: Cyclodextrins in drug delivery. Expert Opin. Drug Deliv. 2(2), 335–351 (2005)

    Article  CAS  Google Scholar 

  12. 12.

    Trotta, F., Zanetti, M., Cavalli, R.: Cyclodextrin-based nanosponges as drug carriers. Beilstein J. Org. Chem. 8(1), 2091–2099 (2012)

    Article  CAS  Google Scholar 

  13. 13.

    Cavalli, R., Trotta, F., Tumiatti, W.: Cyclodextrin-based nanosponges for drug delivery. J. Incl. Phenom. Macrocycl. Chem. 56(1–2), 209–213 (2006). https://doi.org/10.1007/s10847-006-9085-2

    Article  CAS  Google Scholar 

  14. 14.

    Venuti, V., Rossi, B., Mele, A., Melone, L., Punta, C., Majolino, D., Masciovecchio, C., Caldera, F., Trotta, F.: Tuning structural parameters for the optimization of drug delivery performance of cyclodextrin-based nanosponges. Expert Opin. Drug Deliv. 14(3), 331–340 (2017). https://doi.org/10.1080/17425247.2016.1215301

    Article  PubMed  CAS  Google Scholar 

  15. 15.

    Selvamuthukumar, S., Anandam, S., Krishnamoorthy, K., Rajappan, M.: Nanosponges: a novel class of drug delivery system-review. J. Pharm. Pharm. Sci. 15(1), 103–111 (2012)

    Article  Google Scholar 

  16. 16.

    Allahyari, S., Trotta, F., Valizadeh, H., Jelvehgari, M., Zakeri-Milani, P.: Cyclodextrin-based nanosponges as promising carriers for active agents. Expert Opin. Drug Deliv. 16(5), 467–479 (2019). https://doi.org/10.1080/17425247.2019.1591365

    Article  PubMed  CAS  Google Scholar 

  17. 17.

    Ahmed, R.Z., Patil, G., Zaheer, Z.: Nanosponges: a completely new nano-horizon: pharmaceutical applications and recent advances. Drug Dev. Ind. Pharm. 39(9), 1263–1272 (2013). https://doi.org/10.3109/03639045.2012.694610

    Article  PubMed  CAS  Google Scholar 

  18. 18.

    Savjani, K.T., Gajjar, A.K., Savjani, J.K.: Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012, 195727 (2012)

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Tejashri, G., Amrita, B., Darshana, J.: Cyclodextrin based nanosponges for pharmaceutical use: a review. Acta Pharm. 63(3), 335–358 (2013). https://doi.org/10.2478/acph-2013-0021

    Article  PubMed  CAS  Google Scholar 

  20. 20.

    Passarella, R.J., Spratt, D.E., van der Ende, A.E., Phillips, J.G., Wu, H., Sathiyakumar, V., Zhou, L., Hallahan, D.E., Harth, E., Diaz, R.: Targeted nanoparticles that deliver a sustained, specific release of paclitaxel to irradiated tumors. Cancer Res. 70(11), 4550–4559 (2010). https://doi.org/10.1158/0008-5472.can-10-0339

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. 21.

    Swaminathan, S., Cavalli, R., Trotta, F., Ferruti, P., Ranucci, E., Gerges, I., Manfredi, A., Marinotto, D., Vavia, P.: In vitro release modulation and conformational stabilization of a model protein using swellable polyamidoamine nanosponges of β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 68(1–2), 183–191 (2010)

    Article  CAS  Google Scholar 

  22. 22.

    Cavalli, R., Akhter, A.K., Bisazza, A., Giustetto, P., Trotta, F., Vavia, P.: Nanosponge formulations as oxygen delivery systems. Int. J. Pharm. 402(1–2), 254–257 (2010)

    Article  CAS  Google Scholar 

  23. 23.

    Longo, C., Gambara, G., Espina, V., Luchini, A., Bishop, B., Patanarut, A.S., Petricoin III, E.F., Beretti, F., Ferrari, B., Garaci, E.: A novel biomarker harvesting nanotechnology identifies Bak as a candidate melanoma biomarker in serum. Exp. Dermatol. 20(1), 29–34 (2011)

    Article  Google Scholar 

  24. 24.

    Euvrard, É., Morin-Crini, N., Druart, C., Bugnet, J., Martel, B., Cosentino, C., Moutarlier, V., Crini, G.: Cross-linked cyclodextrin-based material for treatment of metals and organic substances present in industrial discharge waters. Beilstein J. Org. Chem. 12, 1826–1838 (2016). https://doi.org/10.3762/bjoc.12.172

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. 25.

    Trotta, F., Tumiatti, W.: Cross-linked polymers based on cyclodextrins for removing polluting agents. U.S. Patent Application No. 10/510792 (2005).

  26. 26.

    Alongi, J., Pošković, M., Frache, A., Trotta, F.: Novel flame retardants containing cyclodextrin nanosponges and phosphorus compounds to enhance EVA combustion properties. Polym. Degrad. Stab. 95(10), 2093–2100 (2010). https://doi.org/10.1016/j.polymdegradstab.2010.06.030

    Article  CAS  Google Scholar 

  27. 27.

    Loftsson, T., Brewster, M.E.: Cyclodextrins as functional excipients: methods to enhance complexation efficiency. J. Pharm. Sci. 101(9), 3019–3032 (2012). https://doi.org/10.1002/jps.23077

    Article  PubMed  CAS  Google Scholar 

  28. 28.

    Saha, S., Roy, A., Roy, K., Roy, M.N.: Study to explore the mechanism to form inclusion complexes of β-cyclodextrin with vitamin molecules. Sci. Rep. 6(1), 35764 (2016). https://doi.org/10.1038/srep35764

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. 29.

    Zoppi, A., Quevedo, M.A., Delrivo, A., Longhi, M.R.: Complexation of sulfonamides with β-cyclodextrin studied by experimental and theoretical methods. J. Pharm. Sci. 99(7), 3166–3176 (2010). https://doi.org/10.1002/jps.22062

    Article  PubMed  CAS  Google Scholar 

  30. 30.

    Garnero, C., Aiassa, V., Longhi, M.: Sulfamethoxazole:hydroxypropyl-beta-cyclodextrin complex: preparation and characterization. J. Pharm. Biomed. Anal. 63, 74–79 (2012). https://doi.org/10.1016/j.jpba.2012.01.011

    Article  PubMed  CAS  Google Scholar 

  31. 31.

    Varghese, B., Suliman, F.O., Al-Hajri, A., Al Bishri, N.S.S., Al-Rwashda, N.: Spectral and theoretical study on complexation of sulfamethoxazole with β- and HPβ-cyclodextrins in binary and ternary systems. Spectrochim. Acta. A 190, 392–401 (2018). https://doi.org/10.1016/j.saa.2017.09.060

    Article  CAS  Google Scholar 

  32. 32.

    Diez, N.M., de la Peña, A.M., García, M.C.M., Gil, D.B., Cañada-Cañada, F.: Fluorimetric determination of sulphaguanidine and sulphamethoxazole by host-guest complexation in β-cyclodextrin and partial least squares calibration. J. Fluoresc. 17(3), 309–318 (2007). https://doi.org/10.1007/s10895-007-0174-4

    Article  PubMed  CAS  Google Scholar 

  33. 33.

    Zoppi, A., Delrivo, A., Aiassa, V., Longhi, M.R.: Binding of sulfamethazine to β-cyclodextrin and methyl-β-cyclodextrin. AAPS PharmSciTech 14(2), 727–735 (2013). https://doi.org/10.1208/s12249-013-9958-9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. 34.

    Muthu Prabhu, A.A., Venkatesh, G., Rajendiran, N.: Spectral characteristics of sulfa drugs: effect of solvents, pH and β-cyclodextrin. J. Solution Chem. 39(7), 1061–1086 (2010). https://doi.org/10.1007/s10953-010-9559-0

    Article  CAS  Google Scholar 

  35. 35.

    Castiglione, F., Crupi, V., Majolino, D., Mele, A., Rossi, B., Trotta, F., Venuti, V.: Inside new materials: an experimental numerical approach for the structural elucidation of nanoporous cross-linked polymers. J. Phys. Chem. B 116(43), 13133–13140 (2012). https://doi.org/10.1021/jp307978e

    Article  PubMed  CAS  Google Scholar 

  36. 36.

    Higuchi, T., Connors, K.: Phase-solubility techniques. Adv. Anal. Chem. Instrum. 4, 117–212 (1965)

    CAS  Google Scholar 

  37. 37.

    Anandam, S., Selvamuthukumar, S.: Fabrication of cyclodextrin nanosponges for quercetin delivery: physicochemical characterization, photostability, and antioxidant effects. J. Mater. Sci. 49(23), 8140–8153 (2014)

    Article  CAS  Google Scholar 

  38. 38.

    Torne, S.J., Ansari, K.A., Vavia, P.R., Trotta, F., Cavalli, R.: Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded nanosponges. Drug Deliv. 17(6), 419–425 (2010)

    Article  CAS  Google Scholar 

  39. 39.

    Ansari, K.A., Vavia, P.R., Trotta, F., Cavalli, R.: Cyclodextrin-based nanosponges for delivery of resveratrol: in vitro characterisation, stability, cytotoxicity and permeation study. AAPS PharmSciTech 12(1), 279–286 (2011)

    Article  CAS  Google Scholar 

  40. 40.

    Swaminathan, S., Pastero, L., Serpe, L., Trotta, F., Vavia, P., Aquilano, D., Trotta, M., Zara, G., Cavalli, R.: Cyclodextrin-based nanosponges encapsulating camptothecin: physicochemical characterization, stability and cytotoxicity. Eur. J. Pharm. Biopharm. 74(2), 193–201 (2010). https://doi.org/10.1016/j.ejpb.2009.11.003

    Article  PubMed  CAS  Google Scholar 

  41. 41.

    Castiglione, F., Crupi, V., Majolino, D., Mele, A., Panzeri, W., Rossi, B., Trotta, F., Venuti, V.: Vibrational dynamics and hydrogen bond properties of β-CD nanosponges: an FTIR-ATR, Raman and solid-state NMR spectroscopic study. J. Incl. Phenom. Macrocycl. Chem. 75(3), 247–254 (2013). https://doi.org/10.1007/s10847-012-0106-z

    Article  CAS  Google Scholar 

  42. 42.

    Mohamed, M.H., Wilson, L.D., Headley, J.V.: Design and characterization of novel β-cyclodextrin based copolymer materials. Carbohydr. Res. 346(2), 219–229 (2011). https://doi.org/10.1016/j.carres.2010.11.022

    Article  PubMed  CAS  Google Scholar 

  43. 43.

    Swaminathan, S., Vavia, P.R., Trotta, F., Torne, S.: Formulation of betacyclodextrin based nanosponges of itraconazole. J. Incl. Phenom. Macrocycl. Chem. 57(1), 89–94 (2007). https://doi.org/10.1007/s10847-006-9216-9

    Article  CAS  Google Scholar 

  44. 44.

    Rachmawati, H., Edityaningrum, C.A., Mauludin, R.: Molecular inclusion complex of curcumin-β-cyclodextrin nanoparticle to enhance curcumin skin permeability from hydrophilic matrix gel. AAPS PharmSciTech 14(4), 1303–1312 (2013)

    Article  CAS  Google Scholar 

  45. 45.

    Sambasevam, K.P., Mohamad, S., Sarih, N.M., Ismail, N.A.: Synthesis and characterization of the inclusion complex of β-cyclodextrin and azomethine. Int. J. Mol. Sci. 14(2), 3671–3682 (2013)

    Article  CAS  Google Scholar 

  46. 46.

    Dora, C.P., Trotta, F., Kushwah, V., Devasari, N., Singh, C., Suresh, S., Jain, S.: Potential of erlotinib cyclodextrin nanosponge complex to enhance solubility, dissolution rate, in vitro cytotoxicity and oral bioavailability. Carbohydr. Polym. 137, 339–349 (2016). https://doi.org/10.1016/j.carbpol.2015.10.080

    Article  PubMed  CAS  Google Scholar 

  47. 47.

    Darandale, S., Vavia, P.: Cyclodextrin-based nanosponges of curcumin: formulation and physicochemical characterization. J. Incl. Phenom. Macrocycl. Chem. 75(3–4), 315–322 (2013)

    Article  CAS  Google Scholar 

  48. 48.

    Guo, Z., Zhang, Q., Zou, H., Guo, B., Ni, J.: A method for the analysis of low-mass molecules by MALDI–TOF mass spectrometry. Anal. Chem. 74(7), 1637–1641 (2002)

    Article  CAS  Google Scholar 

  49. 49.

    Zhu, X., Papayannopoulos, I.A.: Improvement in the detection of low concentration protein digests on a MALDI TOF/TOF workstation by reducing alpha-cyano-4-hydroxycinnamic acid adduct ions. J. Biomol. Tech. 14(4), 298–307 (2003)

    PubMed  PubMed Central  Google Scholar 

  50. 50.

    Kesimli, B., Topacli, A., Topacli, C.: An interaction of caffeine and sulfamethoxazole: studied by IR spectroscopy and PM3 method. J. Mol. Struct. 645(2), 199–204 (2003). https://doi.org/10.1016/S0022-2860(02)00561-6

    Article  CAS  Google Scholar 

  51. 51.

    Kesimli, B., Topacli, A.: Infrared studies on Co and Cd complexes of sulfamethoxazole. Spectrochim. Acta A 57(5), 1031–1036 (2001)

    Article  Google Scholar 

  52. 52.

    Singh, V., Xu, J., Wu, L., Liu, B., Guo, T., Guo, Z., York, P., Gref, R., Zhang, J.: Ordered and disordered cyclodextrin nanosponges with diverse physicochemical properties. RSC Adv. 7(38), 23759–23764 (2017). https://doi.org/10.1039/C7RA00584A

    Article  Google Scholar 

  53. 53.

    McClements, D.J.: Encapsulation, protection, and release of hydrophilic active components: potential and limitations of colloidal delivery systems. Adv. Colloid Interface Sci. 219, 27–53 (2015)

    Article  CAS  Google Scholar 

  54. 54.

    Liang, W., Yang, C., Zhou, D., Haneoka, H., Nishijima, M., Fukuhara, G., Mori, T., Castiglione, F., Mele, A., Caldera, F., Trotta, F., Inoue, Y.: Phase-controlled supramolecular photochirogenesis in cyclodextrin nanosponges. Chem. Commun. 49(34), 3510–3512 (2013). https://doi.org/10.1039/C3CC40542G

    Article  CAS  Google Scholar 

  55. 55.

    Wu, Y., Joseph, S., Aluru, N.R.: Effect of cross-linking on the diffusion of water, ions, and small molecules in hydrogels. J. Phys. Chem. B 113(11), 3512–3520 (2009). https://doi.org/10.1021/jp808145x

    Article  PubMed  CAS  Google Scholar 

  56. 56.

    Sharma, R., Pathak, K.: Polymeric nanosponges as an alternative carrier for improved retention of econazole nitrate onto the skin through topical hydrogel formulation. Pharm. Dev. Technol. 16(4), 367–376 (2011). https://doi.org/10.3109/10837451003739289

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This project has been supported by Marmara University Scientific Research Projects Coordination Unit under grant number SAG-C-YLP-081117-0612. We would like to thank to Biofarma Pharmaceuticals (Turkey) for providing Sulfamethoxazole as a gift. The authors appreciate Dr. Jürgen H. Gross at Institute of Organic Chemistry of the University of Heidelberg (Germany) for MALDI–TOF MS analyses. We thank to Fatih Serdar SAYIN from Marmara University, Faculty of Technology, Department of Electrical-Electronics Engineering for SEM studies.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Gökçen Yaşayan.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 568 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yaşayan, G., Şatıroğlu Sert, B., Tatar, E. et al. Fabrication and characterisation studies of cyclodextrin-based nanosponges for sulfamethoxazole delivery. J Incl Phenom Macrocycl Chem 97, 175–186 (2020). https://doi.org/10.1007/s10847-020-01003-z

Download citation

Keywords

  • β-Cyclodextrin
  • Nanosponge
  • Cross-linking
  • 1,1′-Carbonyldiimidazole
  • Sulfamethoxazole
  • Drug release