Pharmacokinetic and Pharmacodynamic Studies of Poly(amidoamine) Dendrimer Based Simvastatin Oral Formulations for the Treatment of Hypercholesterolemia

Abstract

The aim of this investigation was to evaluate the in vivo potential of poly(amidoamine) dendrimers (PAMAM) based simvastatin (SMV) formulations as nanoscale drug delivery units for controlled release action of simvastatin. Drug-dendrimer complexes were prepared and characterized by Fourier transform infrared (FTIR) spectroscopy. In a pharmacodynamic study, the percent increase in cholesterol was less with PAMAM dendrimer formulations as compared to pure drug. The cholesterol level was increased to 20.92% with pure SMV, whereas it was 11.66% with amine dendrimer, 11.49% with PEGylated dendrimer, and 10.86% with hydroxyl dendrimer formulations. Reduction in the increase in triglyceride and low density lipoprotein level was also more prominent with the drug-dendrimer formulations. The order of increase in high density lipoprotein level was PEGylated PAMAM-SMV (4.04%) > PAMAM-amine-SMV (2.57%) > PAMAM-hydroxyl-SMV (1.48%) > pure SMV (1.09%). Dendrimer-SMV formulations showed better pharmacokinetic performances than pure SMV suspension. The peak plasma SMV concentration increased from 2.3 μg/mL with pure SMV to 3.8 μg/mL with dendrimer formulations. The dendrimer mediated formulation had 3-5 times more mean SMV residence time than pure SMV. Furthermore, SMV absorption and elimination rates were decreased significantly, showing controlled release of SMV from the dendrimer formulations.

Investigation of Poly(amidoamine) Dendrimer Based Simvastatin Oral Formulations: Pharmacokinetic and Pharmacodynamic Studies

“…These PD profiles suggested that the slow release kinetics of SMV from PEGylated dendrimer-SMV complexes sustained a steady-state SMV concentration in the blood. All these results well align with in vitro release kinetics of SMV from this formulation [5].…”

Dendrimer nanotechnology for enhanced formulation and controlled delivery of resveratrol

“…Enhancement of solubility along with stability and possible permeability of drug owing to the dendrimer helped simvastatin achieve better pharmacokinetic performance compared to the drug alone in animal models (Fig. ) …”

“…Plasma concentration of simvastatin released from suspension and drug–dendrimer formulations with amine (DN2), hydroxyl (DO2), and pegylated (DP2) surfaces …”

Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer

“…Dendrimers have an ideal structure to develop a targeted drug delivery system where drug molecules can be encapsulated in the internal cavities while conjugating a targeting ligand to the free functional groups on the surface. Dendrimers are hyper-branched, nano-sized and multifunctional carrier systems having open internal cavities and free functional groups on their surface 22 23 24 25 26 27 .…”