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

Research output: Contribution to journalArticle

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

Fingerprint

Dendrimers
Triamcinolone Acetonide
Retinal Pigments
Epithelial Cells
Retinal Pigment Epithelium
Vascular Endothelial Growth Factor A
Anti-Inflammatory Agents
Retinal Diseases
Macular Edema
Macular Degeneration
Microglia
Diabetic Retinopathy
Hydrophobic and Hydrophilic Interactions
Solubility
Steroids
Inflammation
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Cite this

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title = "Intracellular delivery of dendrimer triamcinolone acetonide conjugates into microglial and human retinal pigment epithelial cells",
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.",
keywords = "Anti-inflammatory, Anti-VEGF, Dendrimer, Human retinal pigment epithelium, Microglial cells, Ocular drug delivery, Triamcinolone acetonide",
author = "Kambhampati, {Siva Pramodh} and Mishra, {Manoj K.} and Panagiotis Mastorakos and Yumin Oh and Lutty, {Gerard Anthony} and Kannan Rangaramanujam",
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AU - Kambhampati, Siva Pramodh

AU - Mishra, Manoj K.

AU - Mastorakos, Panagiotis

AU - Oh, Yumin

AU - Lutty, Gerard Anthony

AU - Rangaramanujam, Kannan

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AB - 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.

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