The aim of this study was preparation and optimisation of a controlled-release delivery system to decrease the dose-dependent side effects of gentamicin. Hydrogel nanoparticles composed of a polycationic polymer (chitosan) and an inorganic polyanion (sodium tripolyphosphate) were fabricated in the presence of gentamicin. An experimental design was drawn upon to determine the optimum condition of nanoparticle preparation. Various features of the nanoparticles including drug loading parameters, particle size distribution, zeta potential and in vitro drug release profile were evaluated. Ultimately, the antimicrobial activity of the gentamicin-loaded nanoparticles was analysed by determination of the minimum inhibitory concentration (MIC) and the potency test. As a result, the nanocarriers with an average size of about 250 nm (unloaded) and 493 nm (gentamicin-loaded) were obtained with unimodal distribution and a notable polydispersity index (≤0.3). The drug loading efficiency was between 28 and 32%. The gradual and sustained releases (∼90%) of gentamicin were achieved in 24 h. The MIC and potency test showed no significant decrease in the antibacterial activity of gentamicin-loaded nanoparticles. The outcomes demonstrated that the optimised chitosan nanogels prepared in this study can be considered as a suitable carrier for a controlled release system.

References

1. 1)
  - 4. Paños, I., Acosta, N., Heras, A.: ‘New drug delivery systems based on chitosan’, Curr. Drug Discov. Technol., 2008, 5, (4), pp. 333–341.
2. 2)
  - 6. Phaechamud, T., Issarayungyuen, P., Pichayakorn, W.: ‘Gentamicin sulfate-loaded porous natural rubber films for wound dressing’, Int. J. Biol. Macromol., 2016, 85, pp. 634–644.
3. 3)
  - 5. Schiffman, J.D., Schauer, C.L.: ‘Cross-linking chitosan nanofibers’, Biomacromolecules, 2007, 8, (2), pp. 594–601.
4. 4)
  - 14. Singh, R., Lillard, J.W.Jr.: ‘Nanoparticle-based targeted drug delivery’, Exp. Mol. Pathol., 2009, 86, (3), pp. 215–223.
5. 5)
  - 7. Bartal, C., Danon, A., Schlaeffer, F., et al: ‘Pharmacokinetic dosing of aminoglycosides: a controlled trial’, Am. J. Med., 2003, 114, (3), pp. 194–198.
6. 6)
  - 3. Madhusudhan, B., Kumara, J.B.V.: ‘Formulation and evaluation of atorvastatin calcium loaded chitosan nanoparticles’, Int. J. Pharm. Bio Sci., 2015, 6, (3), pp. 50–58.
7. 7)
  - 1. Hamidi, M., Azadi, A., Rafiei, P.: ‘Hydrogel nanoparticles in drug delivery’, Adv. Drug Deliv. Rev., 2008, 60, (15), pp. 1638–1649.
8. 8)
  - 10. Zhao, Y., Fang, L., Tan, T.: ‘Optimization of the preparation of a poly (aspartic acid) superabsorbent resin with response surface methodology’, J. Appl. Polym. Sci., 2006, 102, (3), pp. 2616–2622.
9. 9)
  - 8. Goitein, K., Michel, J., Sacks, T.: ‘Penetration of parenterally administered gentamicin into the cerebrospinal fluid in experimental meningitis’, Chemotherapy, 1975, 21, (3-4), pp. 181–188.
10. 10)
  - 15. Lu, X.Y., Wu, D.C., Li, Z.J., et al: ‘Polymer nanoparticles’, in Villaverde, A. (Ed.): ‘Nanoparticles in translational science and medicine’ (Academic Press, 2011, 1st edn), pp. 307–308.
11. 11)
  - 12. Dafalen, N.A., Semwal, U.P., Agarwal, P.K., et al: ‘Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations’, J. Pharm. Anal., 2015, 5, (1), pp. 18–26.
12. 12)
  - 13. Singh, V.K., Soni, A.B., Singh, R.K.: ‘Process optimization studies of malachite green dye adsorption onto eucalyptus (Eucalyptus globulus) wood biochar using response surface methodology’, Orient. J. Chem., 2016, 32, (5), pp. 2621–2631.
13. 13)
  - 9. Rubinstein, E., Goldfarb, J., Keren, G., et al: ‘The penetration of gentamicin into the vitreous humor in man’, Invest. Ophthalmol. Vis. Sci., 1983, 24, (5), pp. 637–639.
14. 14)
  - 2. Gao, P., Nie, X., Zou, M., et al: ‘Recent advances in materials for extended-release antibiotic delivery system’, J. Antibiot., 2011, 64, (9), pp. 625–634.
15. 15)
  - 11. United States Pharmacopeia and National Formulary (USP 39-NF 34). Rockville, MD: United States Pharmacopeia Convention, 2016, vol. 1, pp. 1143–1144.

Factorial design analysis and optimisation of chitosan-based nanogels as controlled release system for gentamicin

References

Related content