Oral Codelivery of WR-1065 Using Curcumin-Linked ROS-Sensitive Nanoparticles for Synergistic Radioprotection

Abstract

Protecting the body from radiation damage is a huge medical challenge. Amifostine and curcumin are both effective radioprotectants, but their use has been greatly restricted due to various reasons including low bioavailability. Nanoscale drug delivery systems of poly(ethylene glycol)−poly(ε-caprolactone) copolymers can improve the bioavailability of drugs due to excellent biocompatibility, biodegradability, and long circulation characteristics. In this study, a new reactive oxygen speciessensitive nanocarrier fabricated by linking curcumin and thioketal to poly(ethylene glycol)−poly(ε-caprolactone) polymer was used for delivery of WR-1065 (the active ingredient of amifostine). The content of curcumin in this polymer was about 7.6%, and the drug loading of WR-1065 was 44%. The WR-1065-loaded nanoparticles (NPs) had an average size of 128.6 nm and uniform spherical morphology. These WR-1065-loaded NPs reduced the metabolism of curcumin and WR-1065 in the gastrointestinal tract and could be well absorbed by cells and distributed to multiple organs. Compared with a single drug, oral administration of WR-1065-loaded NPs demonstrated obvious radioprotective effects on the hematopoietic system and prevented intestinal injury. The 30-day survival rate after half-lethal dose (7.2 Gy) of total body irradiation was 100%. In general, WR-1065-loaded NPs improved the oral bioavailability of WR-1065 and curcumin. This multifunctional nanocarrier provides a possibility for combination therapy in treating ionizing radiation damage.

One-Pot Self-Assembly of Core-Shell Nanoparticles within Fibers by Coaxial Electrospinning for Intestine-Targeted Delivery of Curcumin

“…The construction of a nanoscale transport system is an effective solution to solve this problem [ 14 , 15 ]. Clinical studies have found that systems with nanocarriers can significantly enhance Cur’s bioavailability and stability and therefore make it more applicable [ 16 ].…”

Nanodrugs with intrinsic radioprotective exertion: Turning the double‐edged sword into a single‐edged knife

“…In contrast, although many plant extracts have shown excellent radioprotective effects with lower toxicity, most of their applications are also limited due to the poor water solubility, intestinal instability, poor absorption, short circulating time, and low bioavailability. [ 76 ] For instance, although resveratrol has been widely accepted to implement the antioxidant and anti‐radiation actions, many researchers argue that the studies related to the absorption, metabolism, and bioavailability of resveratrol in humans are still inadequate, and the interactions between its pharmacological effect with other therapies especially such as radiotherapy are still unclear. As a result, the biological mechanisms of its action need to be further determined.…”

Advances of Amifostine in Radiation Protection: Administration and Delivery

“…73 Yahong Liu et al connected curcumin and thioketal to poly(ethylene glycol)poly(ε-caprolactone) polymer to prepare reactive oxygen species-sensitive nanocarriers for WR-1065 delivery. 74 The preparation reduced the metabolism of curcumin and WR-1065 in the gastrointestinal tract, which was fully absorbed by cells and distributed to multiple organs, improving oral bioavailability. Compared with a single drug, oral WR-1065loaded NPs showed a significant protective effect on the radiation of the hematopoietic system and had a protective effect on the intestine.…”