Delivering curcumin and gemcitabine in one nanoparticle platform for colon cancer therapy

Abstract

As gemcitabine and curcumin have different targets in colon cancer cells, combination of them may bring benefits. Here, curcumin and gemcitabine were formulated into a biodegradable polymer platform for combination therapy for treatment of colon cancer. In doing so, a FDA approved biodegradable polymer mPEG-PLA (methoxyl-polyethylen glycol-block-polylactide) was chosen as a drug carrier. At first, a mPEG-PLA/Gem conjugate was designed. Thereafter, simply using this drug conjugate to encapsulate curcumin, polymeric micelles loaded with both curcumin and gemcitabine were obtained. Varying the feed ratio of the two drugs, a series of micelles with different ratios of curcumin and gemcitabine could be prepared. The as-prepared dual drug loaded nanoparticles showed spherical structures with mean diameters ranging from 118 nm to 149 nm by DLS. In vitro, M(Cur/Gem) almost showed greater synergy than free combination of curcumin/gemcitabine. In vivo, better antitumor effect and lower systemic toxicity of M(Cur/Gem) were observed on a murine xenograft model. The present study provides the possibility of combining curcumin and gemcitabine in a nanoparticle formulation, and translation of this combination may bring benefits for future clinical use.