Complex polymeric nanomicelles co-delivering doxorubicin and dimethoxycurcumin for cancer chemotherapy

Abstract

Combinational therapy is a new trend in medical sciences to achieve a maximum therapeutic response of the drugs with a comparatively low incidence of severe adverse effects. To overcome the challenges of conventional formulations for cancer chemotherapy, a polymer-based complex nanomicellar system, namely CPM-DD, was developed co-delivering the anti-cancer agent doxorubicin (DOX) and potent antioxidant dimethoxycurcumin (DiMC). The optimal mass ratio of DOX/DiMC in CPM-DD was determined as 1:6 due to the synergistic antiproliferative effect from in vitro cytotoxicity assay, while the biocompatible diblock copolymer of mPEG2000-PLA5000 was selected for drug entrapment at an optimal feeding ratio of 9:1 to both drugs together. The uniform particles of CPM-DD with suitable particle size (∼30 nm) and stable drug loading content (>9%) could be reliably obtained by self-assembly with the encapsulation yield up to 95%. Molecular dynamics simulation revealed the interaction mechanism responsible for forming these complex nanomicelles. The acid-base interaction between two drugs would significantly improve their binding with the copolymer, thus leading to good colloidal stability and controlled drug release characteristics of CPM-DD. Systematic evaluation based on the MCF-7 breast tumor-bearing nude mice model further demonstrated the characteristics of tissue biodistribution of both drugs delivered by CPM-DD, which were closely related to the drug loading pattern and greatly responsible for the improved anti-cancer potency and attenuated toxicity of this complex formulation. Therefore, all the findings indicated that CPM-DD would be a good alternative to the conventional formulations of DOX and worthy of clinical application for cancer chemotherapy.

Development of nanocubosomes co-loaded with dual anticancer agents curcumin and temozolomide for effective colon cancer therapy

“…However, co-administration of chemotherapeutic drugs usually fails to attain its full therapeutic efficacy due to its poor water solubility, rapid clearance, and off-target toxicities. To combat this problem, chemotherapeutic drugs have been co-loaded into nanodrug delivery systems, which can enhance the therapeutic activity of chemotherapeutic drugs by enabling their enhanced cell penetration and intracellular distribution, and reducing their toxic effects on healthy cells (Bronze-Uhle et al., 2017 ; Li et al., 2021 ; Sohail et al., 2022 ).…”

Nanomedicine-Based Drug-Targeting in Breast Cancer: Pharmacokinetics, Clinical Progress, and Challenges

“…The acid–base interaction enhances the drug binding with the copolymer, resulting in good colloidal stability and controlled drug release. A systematic evaluation of MCF-7 breast tumor-bearing nude mice showed enhanced anticancer potency with attenuated toxicity . Therefore, from the above finding, it is summarized that DOX/DiMC complex nanomicelles could be a better alternative to the conventional formulations of DOX.…”

“…Researchers have optimized DOX and dimethoxy curcumin (DiMC) coloaded nanomicelles at a ratio of 1:6, while mPEG2000-PLA5000 biocompatible diblock copolymer was considered at a fixed 9:1 ratio for both drugs. This approach addresses challenges in conventional cancer chemotherapy formulations . The developed nanomicelles had an average particle size of 30 nm, with stable drug loading of over 9% and an EE of 95%.…”

Modulation of Macrophages Using Nanoformulations with Curcumin to Treat Inflammatory Diseases: A Concise Review

“…The hydrophobic core of the micelles can be used as a reservoir to incorporate hydrophobic drugs [ 57 ] to solubilize drugs with poor water solubility, showing great potential in drug delivery systems. Sohail et al [ 58 ] designed polymeric micelles (CPM-DD) composed of amphiphilic diblock copolymers (mPEG-PLA) to co-encapsulate dimethoxycurcumin (DiMC) and doxorubicin (DOX). The cumulative release rate of DOX in CPM-DD was as high as 84% within 72 h, while DiMC exhibited a sustained release profile, reaching about 40% release within 72 h, indicating strong attachments of DiMC to the constructed micelles.…”