Pharmaceutical Research

, 35:117 | Cite as

Tacrolimus Loaded PEG-Cholecalciferol Based Micelles for Treatment of Ocular Inflammation

  • Shallu Kutlehria
  • Imran Vhora
  • Arvind Bagde
  • Nusrat Chowdhury
  • Gautam Behl
  • Ketan Patel
  • Mandip Singh
Research Paper



Poor corneal permeability, nasolacrimal drainage and requirement of chronic administration are major drawbacks of existing therapies for ocular inflammation. Hence, we designed topical micelles of PEG2000 conjugated with cholecalciferol (PEGCCF).


Integrin targeted tacrolimus loaded PEGCCF micelles (TTM) were prepared by solvent diffusion evaporation method and characterized for particle size, osmolality, encapsulation efficiency and drug loading. Therapeutic potential of TTM was evaluated in benzalkonium chloride induced ocular inflammation model in BALB/c mice. Corneal flourescein staining and histopathological analysis of corneal sections was performed.


TTM had a particle size of 45.3 ± 5.3 nm, encapsulation efficiency (88.7 ± 0.9%w/w) and osmolality of 292–296 mOsmol/Kg. TTM significantly reduced the corneal fluorescence as compared to tacrolimus suspension (TACS). H&E staining showed that TTM could restore corneal epithelial thickness, reduce stromal edema (p < 0.05) and decrease number of inflammatory cells (p < 0.01) compared with TACS. Immunohistochemistry analysis demonstrated lower expression of Ki67 + ve cells (p < 0.05) and IL-6 throughout the cornea against TACS (p < 0.01) and the control (p < 0.001).


TTM is an innovative delivery system for improving ocular inflammation due to a) integrin targeting b) PEGCCF in the form of carrier and c) anti-inflammatory and synergistic effect (due to Pgp inhibition) with TAC.


micelles ocular inflammation tacrolimus targeted 



Antigen presenting cells


Benzalkonium chloride


C-reactive protein






1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]


Human corneal epithelial cells

IFN- γ





Intraocular pressure


Langerhans cells


Polyethylene glycol methyl ether (average Mn~2000)


Nuclear factor of activated T cells


Poly-dispersity index


Polyethylene glycol


PEG2000 conjugated with cholecalciferol






Sodium fluorescein




Tacrolimus suspension




Tumor necrosis factor


Targeted tacrolimus loaded micelles




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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of Pharmacy and Pharmaceutical SciencesFlorida A&M UniversityTallahasseeUSA
  2. 2.College of Pharmacy and Health SciencesSt. John’s UniversityNew YorkUSA

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