Skip to main content
Log in

Niosome-Encapsulated Gentamicin for Ophthalmic Controlled Delivery

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The objective of the present research was to investigate the feasibility of using non-ionic surfactant vesicles (niosomes) as carriers for the ophthalmic controlled delivery of a water soluble local antibiotic; gentamicin sulphate. Niosomal formulations were prepared using various surfactants (Tween 60, Tween 80 or Brij 35), in the presence of cholesterol and a negative charge inducer dicetyl phosphate (DCP) in different molar ratios and by employing a thin film hydration technique. The ability of these vesicles to entrap the studied drug was evaluated by determining the entrapment efficiency %EE after centrifugation and separation of the formed vesicles. Photomicroscopy and transmission electron microscopy as well as particle size analysis were used to study the formation, morphology and size of the drug loaded niosomes. Results showed a substantial change in the release rate and an alteration in the %EE of gentamicin sulphate from niosomal formulations upon varying type of surfactant, cholesterol content and presence or absence of DCP. In-vitro drug release results confirmed that niosomal formulations have exhibited a high retention of gentamicin sulphate inside the vesicles such that their in vitro release was slower compared to the drug solution. A preparation with 1:1:0.1 molar ratio of Tween 60, cholesterol and DCP gave the most advantageous entrapment (92.02% ± 1.43) and release results (Q8h = 66.29% ± 1.33) as compared to other compositions. Ocular irritancy test performed on albino rabbits, showed no sign of irritation for all tested niosomal formulations.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. A. Cabanes, F. Reig, and J.M. Garcia-Anton. Evaluation of free and liposome-encapsulated gentamicin for intramuscular sustained release in rabbits. Res. Vet. Sci. 64:213–217 (1998).

    Article  PubMed  CAS  Google Scholar 

  2. N.C. Megoulas, and M.A. Koupparis. Development and validation of a novel LC/ELSD method for the quantitation of gentamicin sulphate components in pharmaceuticals. J. Pharm. Biomed. Anal. 36:73–79 (2004).

    Article  PubMed  CAS  Google Scholar 

  3. I.P. Kaur, A. Garg, A.K. Singla, and D. Aggarwal. Vesicular systems in ocular delivery: an overview. Int. J. Pharm. 269:1–14 (2004).

    Article  PubMed  CAS  Google Scholar 

  4. J. Frucht-Pery, H. Mechoulam, C.S. Siganos, P. Ever-Hadani, M. Shapiro, and A. Domb. Iontophoresis–gentamicin delivery into the rabbit cornea, using a hydrogel delivery probe. Exp. Eye Res. 78:745–749 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. M.J. Blanco-Prıeto, C. Lecaroz, M.J. Renedo, J. Kunkova, and C. Gamazo. In vitro evaluation of gentamicin released from microparticles. Int. J. Pharm. 242:203–206 (2002).

    Article  PubMed  Google Scholar 

  6. R.E. Records. Gentamicin in ophthalmology. Surv. Ophthalmol. 21:49–58 (1976).

    Article  PubMed  CAS  Google Scholar 

  7. V. Baeyens, V. Kaltsatos, B. Boisramé, E. Varesio, J.L. Veuthey, M. Fathi, L.P. Balant, M. Gex-Fabry, and R. Gurny. Optimized release of dexamethasone and gentamicin from a soluble ocular insert for the treatment of external ophthalmic infections. J. Control Release. 52:215–220 (1998).

    Article  PubMed  CAS  Google Scholar 

  8. V. Baeyens, O. Felt-Baeyens, S. Rougier, S. Pheulpin, B. Boisramé, and R. Gurny. Clinical evaluation of bioadhesive ophthalmic drug inserts (BODI®) for the treatment of external ocular infections in dogs. J. Control Release. 85:163–168 (2002).

    Article  PubMed  CAS  Google Scholar 

  9. D.G. Colo, and Y. Zambito. A study of release mechanisms of different ophthalmic drugs from erodible ocular inserts based on poly (ethylene oxide). Eur. J. Pharm. Biopharm. 54:193–199 (2002).

    Article  PubMed  Google Scholar 

  10. I.F. Uchegbu, and S.P. Vyas. Non ionic surfactant based vesicles (niosomes) in drug delivery. Int. J. Pharm. 172:33–70 (1998).

    Article  CAS  Google Scholar 

  11. M. Carafa, E. Santucci, F. Alhaique, T. Coviello, E. Murtas, F.M. Riccieri, G. Lucania, and M.R. Torrisi. Preparation and properties of new unilamellar non-ionic surfactant vesicles. Int. J. Pharm. 160:51–59 (1998).

    Article  CAS  Google Scholar 

  12. M. Carafa, E. Santucci, and G. Lucania. Lidocaine-loaded non ionic surfactant vesicles: characterization and in vitro permeation studies. Int. J. Pharm. 231:21–32 (2002).

    Article  PubMed  CAS  Google Scholar 

  13. M.F. Saettone, G. Perini, M. Carafa, E. Santucci, and F. Alhaique. Non-ionic surfactant vesicles as ophthalmic carriers for cyclopentolate. A preliminary evaluation. S. T. P. Pharma. Sci. 6:94–98 (1996).

    Google Scholar 

  14. S.P. Vyas, N. Mysore, V. Jaittley, and N. Venkatesan. Discoidal niosome based controlled ocular delivery of timolol maleate. Pharmazie. 53:466–469 (1998).

    PubMed  CAS  Google Scholar 

  15. K. Green, and S. Downs. Ocular penetration of pilocarpine in rabbits. Arch. Ophthalmol. 93:1165–1168 (1975).

    PubMed  CAS  Google Scholar 

  16. N. Keller, D. Moore, D. Carper, and A. Longiwell. Increased corneal permeability by the dual effect of the transient tear film acidification and exposure to benzalkonium chloride. Exp. Eye Res. 30:203–210 (1980).

    Article  PubMed  CAS  Google Scholar 

  17. N.L. Burstein. Preservative alteration of corneal permeability in human and rabbits. Invest. Ophthalmol. Vis. Sci. 25:1453 (1984).

    PubMed  CAS  Google Scholar 

  18. I.P. Kaur, and R. Smitha. Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev. Ind. Pharm. 28:353–369 (2002).

    Article  PubMed  CAS  Google Scholar 

  19. A.J. Baillie, A.T. Florence, L.R. Hume, G.T. Muirhead, and A. Rogerson. The preparation and properties of niosomes non-ionic surfactant vesicles. J. Pharm. Pharmacol. 37:863–868 (1985).

    PubMed  CAS  Google Scholar 

  20. R. Agarwal, O.P. Katare, and S.P. Vyas. Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. Int. J. Pharm. 228:43–52 (2001).

    Article  PubMed  CAS  Google Scholar 

  21. X. Zhang, U.P. Wyss, D. Pichora, and M.F.A. Goosen. Biodegradable controlled antibiotic release devices for osteomyelitis: optimization of release properties. J. Pharm. Pharmacol. 46:718–24 (1994).

    PubMed  CAS  Google Scholar 

  22. K. Ruckmani, B. Jayakar, and S.K. Ghosal. Nonionic surfactant vesicles (niosomes) of cytarabine hydrochloride for effective treatment of leukemia: encapsulation, storage and in vitro release. Drug Dev. Ind. Pharm. 26:217–222 (2000).

    Article  PubMed  CAS  Google Scholar 

  23. M. Benchimol, B. Piva, L. Campanati, and W. De Souza. Visualization of the funis of Giardia lamblia by high-resolution field emission scanning electron microscopy-new insights. J. Struc. Bio. 147:102–115 (2004).

    Article  Google Scholar 

  24. P. Arunothayanun, M.S. Bernard, D.Q.M. Craig, I.F. Uchegbu, and A.T. Florence. The effect of processing variables on the physical characteristics of non-ionic surfactant vesicles (niosomes) formed from a hexadecyl diglycerol ether. Int. J. Pharm. 201:7–14 (2000).

    Article  PubMed  CAS  Google Scholar 

  25. O.N. El-Gazayerly, and A.H. Hikal. Preparation and evaluation of acetazolamide liposomes as an ocular delivery system. Int. J. Pharm. 158:121–127 (1997).

    Article  CAS  Google Scholar 

  26. G.N. Devaraj, S.R. Parakh, R. Devraj, S.S. Apte, B.R. Rao, and D. Rambhau. Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol. J. Colloid Interface Sci. 251:360–365 (2002).

    Article  PubMed  CAS  Google Scholar 

  27. M. Glavas-Dodov, K. Goracinova, K. Mladenovska, and E. Fredro-Kumbaradzi. Release profile of lidocaine HCl from topical liposomal gel formulation. Int. J. Pharm. 242:381–384 (2002).

    Article  PubMed  CAS  Google Scholar 

  28. N.J. Van Haeringen. Clinical biochemistry of tears. Surv. Ophthalmol. 5:84–96 (1981).

    Article  Google Scholar 

  29. J. Ceulemans, A. Vermeire, E. Adriaens, J.P. Remon, and A. Ludwig. Evaluation of a mucoadhesive tablet for ocular use. J. Control Release. 77:33–344 (2001).

    Article  Google Scholar 

  30. A. Gursoy, E. Kut, and S. Ozkirmli. Co-encapsulation of isoniazid and rifampicin in liposomes and characterization of liposomes by derivative spectroscopy. Int J Pharm. 271:115–123 (2004).

    Article  PubMed  CAS  Google Scholar 

  31. S. Tamilvanana, and S. Benitab. The potential of lipid emulsion for ocular delivery of lipophilic drugs. Eur. J. Pharm. Biopharm. 58:357–368 (2004).

    Article  Google Scholar 

  32. D.G. Colo, S. Burgalassi, P. Chetoni, M.P. Fiaschi, Y. Zambito, and M.F. Saettone. Gel-forming erodible inserts for ocular controlled delivery of ofloxacin. Int. J. Pharm. 215:101–111 (2001).

    Article  PubMed  Google Scholar 

  33. Y. Hao, F. Zhao, N. Li, Y. Yang, and K. Li. Studies on a high encapsulation of colchicine by a niosome system. Int. J. Pharm. 224:73–80 (2002).

    Article  Google Scholar 

  34. R.A. RajaNaresh, G.K. Pillai, N. Udupa, and G. Chandrashekar. Anti-inflammatory activity of niosome encapsulated diclofenac sodium in arthritic rats. Indian. J. Pharmacol. 26:46–48 (1994).

    Google Scholar 

  35. C. Cable. An examination of the effects of surface modifications on the physicochemical and biological properties of non-ionic surfactant vesicles. PhD Thesis. University of Strathclyde, Glasgow, UK (1989).

  36. A. Rogerson, J. Cummings, and A.T. Florence. Adriamycin- loaded niosomes-drug entrapment, stability and release. J. Microencap. 4:321–328 (1987).

    Article  CAS  Google Scholar 

  37. E. Gianasi, F. Cociancich, I.F. Uchegbu, A.T. Florence, and R. Duncan. Pharmaceutical and biological characterization of a doxorubicin polymer conjugate (PK1) entrapped in sorbitan monostearate Span 60 niosomes. Int. J. Pharm. 148:139–148 (1997).

    Article  CAS  Google Scholar 

  38. New RRC. Liposomes: a practical approach, Oxford University Press, Oxford, 1990.

    Google Scholar 

  39. A. Manosroi, P. Wongtrakul, J. Manosroi, H. Sakai, F. Sugawara, M. Yuasa, and M. Abe. Characterization of vesicles prepared with various non ionic surfactants mixed with cholesterol. Colloids Surf. B Biointerfaces. 30:129–138 (2003).

    Article  CAS  Google Scholar 

  40. G.V. Betageri, and D.L. Parsons. Drug encapsulation and release from multilamellar and unilamellar liposomes. Int. J. Pharm. 81:235–241 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ghada Abdelbary.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdelbary, G., El-gendy, N. Niosome-Encapsulated Gentamicin for Ophthalmic Controlled Delivery. AAPS PharmSciTech 9, 740–747 (2008). https://doi.org/10.1208/s12249-008-9105-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-008-9105-1

Key words

Navigation