Long-acting tunable release of amlodipine loaded PEG-PCL micelles for tailored treatment of chronic hypertension

Nanomedicine. 2021 Oct:37:102417. doi: 10.1016/j.nano.2021.102417. Epub 2021 Jun 22.


Hypertension is a chronic condition that requires lifelong therapeutic management. Strict adherence to drug administration timing improves efficacy, while poor adherence leads to safety concerns. In light of these challenges, we present a nanofluidic technology that enables long-acting drug delivery with tunable timing of drug administration using buried gate electrodes in nanochannels. We developed a poly(ethylene glycol) methyl ether-block-poly(ε-caprolactone) (PEG-PCL)-based micellar formulation of amlodipine besylate, a calcium channel blocker for hypertension treatment. The electrostatically charged PEG-PCL micellar formulation enhanced drug solubility and rendered amlodipine responsive to electrostatic release gating in nanochannels for sustained release at clinically relevant therapeutic dose. Using a low-power (<3 VDC) gating potential, we demonstrated tunable release of amlodipine-loaded micelles. Additionally, we showed that the released drug maintained biological activity via calcium ion blockade in vitro. This study represents a proof of concept for the potential applicability of our strategy for chronotherapeutic management of hypertension.

Keywords: Amlodipine; Controlled release; Drug delivery; Hypertension; Micelle encapsulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amlodipine / chemistry
  • Amlodipine / pharmacology*
  • Animals
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Chronic Disease / drug therapy
  • Drug Delivery Systems*
  • Drug Liberation
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / pathology
  • Mice
  • Micelles
  • Myocytes, Cardiac / drug effects
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry


  • Calcium Channel Blockers
  • Calcium Channels
  • Micelles
  • Polyesters
  • Amlodipine
  • polycaprolactone
  • Polyethylene Glycols