Lipid-polyethylene glycol based nano-ocular formulation of ketoconazole

  • Kakkar S
  • Karuppayil S
  • Raut J
 et al. 
  • 22


    Mendeley users who have this article in their library.
  • 18


    Citations of this article.


Ophthalmic mycoses including corneal keratitis or endophthalmitis affects 6-million persons/year and can cause blindness. Its management requires antifungals to penetrate the ocular tissue. Oral use of Ketoconazole (KTZ), the first broad-spectrum antifungal to be marketed, is now restricted to life-threatening infections due to severe adverse effects and drug-interactions. Local use of KTZ loaded nanocarrier system can address its toxicity, poor solubility, photodegradation, permeation and bioavailability issues. Solid lipid nanoparticles (SLNs) comprising Compritol®888 ATO and PEG 600 matrix, were presently prepared using hot high-pressure homogenization. Employing extensive characterization: TEM, NMR, DSC, XRD and FTIR, it is proposed that SLNs comprise of a polyethylene glycol (PEG) core into which KTZ is dissolved. PEG endows the lipid matrix with amorphousness and imperfections; rigidity; and, stability to aggregation, on storage and autoclaving. PEG is a simple, cost-effective and safe polymer with superior solubilizing and surfactant-supporting properties. Without its inclusion KTZ could not be loaded into SLNs. It ensured high incorporation efficiency (70%) of KTZ; small size (126 nm); and, better permeation into the eye. Pharmacokinetic studies indicated 2.5 and 1.6 fold higher bioavailability (AUC) in aqueous and vitreous humor, respectively. Biocompatibility and in vitro (both in corneal and retinal cell lines) and in vivo (in rabbits) ocular safety is the other highlight of developed formulation.

Author-supplied keywords

  • Drug delivery
  • Fungal eye infection
  • Ocular safety
  • Permeation
  • Posterior eye
  • Solid lipid nanoparticles

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • Shilpa Kakkar

  • Sankunny Mohan Karuppayil

  • Jayant S. Raut

  • Fabrizio Giansanti

  • Laura Papucci

  • Nicola Schiavone

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free