Intracellular delivery of dendrimer triamcinolone acetonide conjugates into microglial and human retinal pigment epithelial cells

Siva P. Kambhampati, Manoj K. Mishra, Panagiotis Mastorakos, Yumin Oh, Gerard A. Lutty, Rangaramanujam M. Kannan

Research output: Contribution to journalArticlepeer-review

Abstract

Triamcinolone acetonide (TA) is a potent, intermediate-acting, steroid that has anti-inflammatory and anti-angiogenic activity. Intravitreal administration of TA has been used for diabetic macular edema, proliferative diabetic retinopathy and exudative age-related macular degeneration (AMD). However, the hydrophobicity, lack of solubility, and the side effects limit its effectiveness in the treatment of retinal diseases. In this study, we explore a PAMAM dendrimer-TA conjugate (D-TA) as a potential strategy to improve intracellular delivery and efficacy of TA to target cells. The conjugates were prepared with a high drug payload (∼21%) and were readily soluble in saline. Compared to free TA, D-TA demonstrated a significantly improved toxicity profile in two important target [microglial and human retinal pigment epithelium (RPE)] cells. The D-TA was ∼100-fold more effective than free TA in its anti-inflammatory activity (measured in microglia), and in suppressing VEGF production (in hypoxic RPE cells). Dendrimer-based delivery may improve the efficacy of TA towards both its key targets of inflammation and VEGF production, with significant clinical implications.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume95
DOIs
StatePublished - Sep 1 2015

Keywords

  • Anti-VEGF
  • Anti-inflammatory
  • Dendrimer
  • Human retinal pigment epithelium
  • Microglial cells
  • Ocular drug delivery
  • Triamcinolone acetonide

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

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