Skip to main content
SpringerLink
Log in

Lipid Nanocarrier: an Efficient Approach Towards Ocular Delivery of Hydrophilic Drug (Valacyclovir)

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

Abstract

This research focuses on the fabrication and evaluation of solid lipid nanoparticles (SLNs) for improved ocular delivery of valacyclovir (VAC). Stearic acid and tristearin were selected as the lipid carrier while Poloxamer 188 and sodium taurocholate were used as surfactant and co-surfactant, respectively. The physiochemical properties of the optimized batch (SLN-6) fulfil the prerequisites needed for an ideal ocular formulation like submicron size (202.5 ± 2.56 nm), narrow PDI (0.252 ± 0.06), high zeta potential (−34.4 ± 3.04 mV) and good entrapment efficiency (58.82 ± 2.45%). The in vitro release study of SLN-6 exhibited a sustained release profile (>60% in 12 h). The ex vivo studies performed on excised cornea exhibited enhanced drug permeation of SLNs (22.17 ± 1.41 μg/cm2 h) in comparison to the drug solution (3.78 ± 1.34 μg/cm2 h). Apart, the corneal hydration studies, histopathology and Hen’s Egg Test Chorio Allantoic Membrane (HETCAM) assay, confirmed the non-irritancy of SLNs. The in vivo study confirmed improved ocular bioavailability of VAC from SLN-6 (AUC0–12: 856.47 ± 7.86 μg h/mL) in contrast to the drug solution (AUC0–12: 470.75 ± 8.91 μg h/mL). Hence, the overall studies suggested the potential of SLNs in efficient ocular delivery of a hydrophilic molecule like VAC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Hill GM, Ku ES, Dwarakanathan S. Herpes simplexkeratitis. Dis Mon. 2014;60:239–46.

    Article  PubMed  Google Scholar 

  2. Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25:355–80.

    Article  PubMed  Google Scholar 

  3. Miserocchi E, Modorati G, Galli L, Rama P. Efficacy of valacyclovir vs acyclovir for the prevention of recurrent herpes simplex virus eye disease: a pilot study. Am J Ophthalmol. 2007;144:547–51.

    Article  CAS  PubMed  Google Scholar 

  4. Katragadda S, Gunda S, Hariharan S, Mitra AK. Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections. Int J Pharm. 2008;359:15–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39:1546–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev. 2006;58:1131–5.

    Article  CAS  PubMed  Google Scholar 

  7. Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems-recent advances. Prog Retin Eye Res. 1998;17:33–58.

    Article  CAS  PubMed  Google Scholar 

  8. Kompella UB, Kadam RS, Lee VH. Recent advances in ophthalmic drug delivery. Ther Deliv. 2010;3:435–56.

    Article  Google Scholar 

  9. Willoughby CE, Ponzin D, Ferrari S, Lobo A, Landau K, Omidi Y. Clin Exp Ophthalmol. 2010;38:2–11.

    Article  Google Scholar 

  10. DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011;37:588–98.

    Article  PubMed  Google Scholar 

  11. Toropainen E, Ranta VP, Vellonen KS, et al. Paracellular and passive transcellular permeability in immortalized human corneal epithelial cell culture model. Eur J Pharm Sci. 2003;20:99–106.

    Article  CAS  PubMed  Google Scholar 

  12. Komarova Y, Malik AB. Regulation of endothelial permeability via paracellular and transcellular transport pathways. Annu Rev Physiol. 2010;72:463–93.

    Article  CAS  PubMed  Google Scholar 

  13. Kam KR, Walsh LA, Bock SM, et al. Nanostructure-mediated transport of biologics across epithelial tissue: enhancing permeability via nanotopography. Nano Lett. 2013;13:164–71.

    Article  CAS  PubMed  Google Scholar 

  14. Mehnert W, Mader K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47:165–96.

    Article  CAS  PubMed  Google Scholar 

  15. Seyfoddin A, Shaw J, Al-Kassas R. Solid lipid nanoparticles for ocular drug delivery. Drug Deliv. 2010;17:467–89.

    Article  CAS  PubMed  Google Scholar 

  16. Puglia C, Offerta A, Carbone C, Bonina F, Pignatello R, Puglisi G. Lipid nanocarriers (LNC) and their applications in ocular drug delivery. Curr Med Chem. 2015;22:1589–602.

    Article  CAS  PubMed  Google Scholar 

  17. Liu D, Chen L, Jiang S, et al. Formulation and characterization of hydrophilic drug diclofenac sodium-loaded solid lipid nanoparticles based on phospholipid complexes technology. J Liposome Res. 2014;24:17–26.

    Article  PubMed  Google Scholar 

  18. Basaran E, Demirel M, Sirmagul B, Yazan Y. Cyclosporine-A incorporated cationic solid lipid nanoparticles for ocular delivery. J Microencapsul. 2010;27:37–47.

    Article  CAS  PubMed  Google Scholar 

  19. Cavalli R, Gasco MR, Chetoni P, Burgalassi S, Saettone MF. Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin. Int J Pharm. 2002;238:241–5.

    Article  CAS  PubMed  Google Scholar 

  20. Abul Kalam M, Sultana Y, Ali A, et al. Part II: enhancement of transcorneal delivery of gatifloxacin by solid lipid nanoparticles in comparison to commercial aqueous eye drops. J Biomed Mater Res A. 2013;101:1828–36.

    Article  PubMed  Google Scholar 

  21. Lutfi G, Muzeyyen D. Preparation and characterization of polymeric and lipid nanoparticles of pilocarpine HCl for ocular application. Pharm Dev Technol. 2013;18:701–9.

    Article  PubMed  Google Scholar 

  22. Leonardi A, Bucolo C, Drago F, Salomone S, Pignatello R. Cationic solid lipid nanoparticles enhance ocular hypotensive effect of melatonin in rabbit. Int J Pharm. 2015;478:180–6.

    Article  CAS  PubMed  Google Scholar 

  23. Li R, Jiang S, Liu D, et al. A potential new therapeutic system for glaucoma: solid lipid nanoparticles containing methazolamide. J Microencapsul. 2011;28:134–41.

    Article  CAS  PubMed  Google Scholar 

  24. Mohanty B, Majumdar DK, Mishra SK, Panda AK, Patnaik S. Development and characterization of itraconazole-loaded solid lipid nanoparticles for ocular delivery. Pharm Dev Technol. 2015;20:458–64.

    Article  CAS  PubMed  Google Scholar 

  25. Shah KA, Date AA, Joshi MD, Patravale VB. Solid lipid nanoparticles (SLN) of tretinoin: potential in topical delivery. Int J Pharm. 2007;345:163–71.

    Article  CAS  PubMed  Google Scholar 

  26. Trotta M, Debernardi F, Caputo O. Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique. Int J Pharm. 2003;257:153–60.

    Article  CAS  PubMed  Google Scholar 

  27. ICCVAM-Recommended test method protocol: Hen’s egg test-chorioallantoic membrane (HET-CAM) test method. https://ntp.niehs.nih.gov/iccvam/docs/protocols/ivocular-hetcam.pdf. Accessed on 26 March 2015.

  28. Monti D, Chetoni P, Burgalass S, Najarro M, Saettone MF. Increased corneal hydration induced by potential ocular penetration enhancers: assessment by differential scanning calorimetry (DSC) and by desiccation. Int J Pharm. 2002;232:139–47.

    Article  CAS  PubMed  Google Scholar 

  29. Wilhelmus KR. The Draize eye test. Surv Ophthalmol. 2001;45:493–515.

    Article  CAS  PubMed  Google Scholar 

  30. Lou J, Hu W, Tian R, et al. Optimization and evaluation of a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles. Int J Nanomedicine. 2014;9:2517–25.

    PubMed  PubMed Central  Google Scholar 

  31. Li Q, Li Z, Zeng W, et al. Proniosome-derived niosomes for tacrolimus topical ocular delivery: in vitro cornea permeation, ocular irritation, and in vivo anti-allograft rejection. Eur J Pharm Sci. 2014;62:115–23.

    Article  CAS  PubMed  Google Scholar 

  32. Montenegro L, Bucolo C, Puglisi G. Enhancer effects on in vitro corneal permeation of timolol and acyclovir. Pharmazie. 2003;58:497–501.

    CAS  PubMed  Google Scholar 

  33. Kumar R, Nagarwal RC, Dhanawat M, Pandit JK. In-vitro and in-vivo study of indomethacin loaded gelatin nanoparticles. J Biomed Nanotechnol. 2011;7:325–33.

    Article  CAS  PubMed  Google Scholar 

  34. Lim LT, Ah-kee EY, Collins CE. Common eye drops and their implications for pH measurements in the management of chemical eye injuries. Int J Ophthalmol. 2014;7:1067–8.

    PubMed  PubMed Central  Google Scholar 

  35. Luan X, Skupin M, Siepmann J, Bodmeier R. Key parameters affecting the initial release (burst) and encapsulation efficiency of peptide-containing poly(lactide-co-glycolide) microparticles. Int J Pharm. 2006;324:168–75.

    Article  CAS  PubMed  Google Scholar 

  36. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery system. Acta Pol Pharm. 2010;67:217–23.

    CAS  PubMed  Google Scholar 

  37. Kumar R, Sinha VR. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surf B: Biointerfaces. 2014;117:82–8.

    Article  CAS  PubMed  Google Scholar 

  38. Hamalainen KM, Kontturi K, Auriola S, Murtomaki L, Urtti A. Estimation of pore size and pore density of biomembranes from permeability measurements of polyethylene glycols using an effusion-like approach. J Control Release. 1997;49:97–104.

    Article  CAS  Google Scholar 

  39. Saettone MF, Cheton P, Cerbai R, Mazzanti G, Braghiroli L. Evaluation of ocular permeation enhancers: i effects on corneal transport of four β-blockers, and in vitro/in vivo toxic activity. Int J Pharm. 1996;142:103–13.

    Article  Google Scholar 

Download references

Acknowledgments

The authors are thankful to University Grant Commission (UGC), New Delhi, India for providing financial support to this research work.

Author information

Authors and Affiliations

  1. UIPS, Panjab University, Chandigarh, 160014, India

    Rakesh Kumar & V. R. Sinha

Authors
  1. Rakesh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. R. Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. R. Sinha.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, R., Sinha, V.R. Lipid Nanocarrier: an Efficient Approach Towards Ocular Delivery of Hydrophilic Drug (Valacyclovir). AAPS PharmSciTech 18, 884–894 (2017). https://doi.org/10.1208/s12249-016-0575-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-016-0575-2

Keywords

Search

Navigation