Forming of Demethoxycurcumin Nanocrystallite-Chitosan Nanocarrier for Controlled Low Dose Cellular Release for Inhibition of the Migration of Vascular Smooth Muscle Cells

Abstract

We report an efficient therapeutic approach to inhibit the migration and growth of vascular smooth muscle cells (VSMCs) via a low-dose sustained elution of a water-insoluble drug, demethoxycurcumin (DMC), through a self-assembled amphiphilic carbomethyl-hexanol chitosan (CHC) nanomatrix. Manipulating the cellular internalization and controlled cytotoxic effect of DMC-CHC nanoparticles over the VSMCs was elucidated. The DMC-CHC nanoparticles, which were systematically characterized in terms of structural morphology, surface potential, encapsulation efficiency, and DMC nanocrystallite distribution, exhibited rapid cellular uptake efficiency and considerably improved cytotoxic potency by 2.8 times compared to the free DMC. Under a cytotoxic evaluation, an improved antiproliferative effect and effective inhibition of VSMC migration as a result of highly efficient intracellular delivery of the encapsulated DMC in comparison to free DMC was achieved, which also was confirmed with a subsequent protein analysis. Cellular drug release and distribution of DMC after internalization into VSMCs was experimentally determined. This work may open a potential intracellular medicinal strategy with improved biological and therapeutic efficacy using the DMC-CHC nanoparticles illustrated in this work.

Effects of Nanocurcumin in Rats With Diabetes Induced With Streptozotocin and Nicotinamide: Mrna Expression of B-Type Natriuretic Peptide

“…These findings are in accordance with previous research demonstrating significant improvement of heart tissue damage in rats treated for myopathy [15]. It is also in line with another study that confirmed that nanocurcumin is an antioxidant and anti-inflammatory with good cardiovascular effects, particularly in reducing migration and growth of uncontrolled vascular smooth muscle cells under hyperglycemic conditions [14].…”

“…Previously, oral administration of nanocurcumin (100 mg/kg body weight per day for 30 days) appeared to suppress ROS levels in rats with diabetic cardiomyopathy [14]. However, no research on the effects of nanocurcumin on diabetic cardiomyopathy in rats has been conducted.…”

Demethoxycurcumin, a major active curcuminoid from Curcuma longa, suppresses balloon injury induced vascular smooth muscle cell migration and neointima formation: An in vitro and in vivo study

“…For use in clinical trials, investigations into the creation of DMC‐eluting stents are now underway. Along these lines, a DMC‐carbomethyl‐hexanol chitosan nanomatrix created by our collaborator effectively inhibits VSMC migration in vitro , and a stent including this substance is now being tested to examine its effects on balloon injury induced neointima formation in vivo.…”

“…Recently, it has been reported that curcumin interferes with TNF‐α‐induced migration in human VSMCs by inhibiting matrix metalloproteinases (MMPs) . In addition, a DMC‐carbomethyl‐hexanol chitosan nanomatrix has been shown to effectively inhibit VSMC migration . However, it has not been shown whether DMC and BDMC can interfere with migration to the same extent as curcumin does.…”

Demethoxycurcumin-Loaded Chitosan Nanoparticle Downregulates DNA Repair Pathway to Improve Cisplatin-Induced Apoptosis in Non-Small Cell Lung Cancer

“…In this work, the controlled release of DMC from the nanocrystallite-chitosan nanocarrier has been examined for its possibility to enhance cisplatin-induced apoptosis by downregulation of TP and ERCC1-related pathways in NSCLC. In order to accurately regulate the DMC elution, a highly biocompatible amphiphilic chitosan was employed as a drug carrier [16,17]. This amphiphilic carboxymethyl-hexanoyl chitosan (CHC) is modified from natural chitosan through carboxylmethylation and hexanoyl replacement along the backbone of pristine chitosan.…”