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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
First Online:
Received:
Accepted:

Abstract

Purpose

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).

Methods

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.

Results

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).

Conclusions

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.

KEY WORDS

micelles ocular inflammation tacrolimus targeted 

ABBREVIATIONS

APC

Antigen presenting cells

BKC

Benzalkonium chloride

CRP

C-reactive protein

DCC

Dicyclohexylcarbodiimide

DMAP

4-dimethylaminopyridine

DSPE-PEG2000

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

HCEC

Human corneal epithelial cells

IFN- γ

Interferon-γ

IHC

Immunohistochemistry

iOP

Intraocular pressure

LC

Langerhans cells

mPEG2000

Polyethylene glycol methyl ether (average Mn~2000)

NFAT

Nuclear factor of activated T cells

PDI

Poly-dispersity index

PEG

Polyethylene glycol

PEGCCF

PEG2000 conjugated with cholecalciferol

Pgp

P-glycoprotein

RGD

Arg-Gly-Asp

SF

Sodium fluorescein

TAC

Tacrolimus

TACS

Tacrolimus suspension

TEA

Triethylamine

TNF-α

Tumor necrosis factor

TTM

Targeted tacrolimus loaded micelles

VD3

Cholecalciferol

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© 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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