Self-assembled recombinant human gelatin nanoparticles for anti-cancer drug delivery

Abstract

Conventional chemotherapeutic cancer drugs nonspecifically distributes in the body, thereby limiting the drug achievable within the tumor and also resulting in side effect to normal cells due to excessive toxicities. Cancer nanotherapeutics are rapidly progressing to solve several limitations of conventional drug delivery such as nonspecific biodistribution and targeting, poor oral bioavailability, lack of water solubility, and low therapeutic efficacy. To improve the effect of cancer drugs, nano-carrier system was attracted attention. Nanoparticles are able to carry their loaded active drugs to cancer cells by their enhanced permeability and retention effect and the tumor microenvironment. The α-tocopheryl succinate (α-TOS), vitamin E succinate, is an important anticancer drug due to its cancer cell-specific apoptotic activity. However, free drug has drawbacks of short half-life in the body and poor solubility in water. The purpose of this study was to improve anticancer drug, α-TOS, delivery to cancer site and increase the therapeutic efficacy using polymeric nano-carrier. For this goal, polymeric recombinant human gelatin (rHG) and lipoic acid (LA) conjugate were developed as drug carrier. Hydrophobic modification of rHG led to a formation of self-assembled nanoparticles in aqueous solution by which α-TOS could be encapsulated into the hydrophobic core. Conjugation of rHG-LA is confirmed by FT-IR and TNBS reaction that was colorimetric detection and measurement of primary amines. And loaded α-TOS in rHG-LA nanoparticles were measured by loading efficiency and loading contents using HPLC. In this study, anti-cancer effect of α-TOS loaded rHG-LA nanoparticles and biodistribution of rHG-LA nanoparticles were examined in subcutaneous SCC-7 (Squamous cell carcinoma) tumor bearing mouse model. As a result, self-assembled rHG-LA nanoparticles encapsulated α-TOS with high loading efficiency, showed high tumor targeting ability and enhanced anti-cancer effects with less toxicity in tumor model mice.