Amphiphilic star PEG-Camptothecin conjugates for intracellular targeting

Camptothecin (CPT) is a naturally occurring cytotoxic alkaloid having a broad spectrum of antitumor activity. Unfortunately, it has low bioavailability and encapsulation efficiency, limiting its clinical use. We report on our efforts to develop a novel drug delivery prototype composed of a short, star hydrophilic polyethylene glycol (PEG) backbone and hydrophobic CPT (PEG₄-CPT). The amphiphilic bio-conjugate self-assembles in water into stable spherical nano-particles with a mean diameter of 200 nm and CPT substitution percentage of 27%w/w. CPT is released in a sustained release profile without burst effect. In addition, PEG₄-CPT nano-particles are able to load a co-drug, water soluble or non-water soluble doxorubicin and release them simultaneously with the free CPT. The biological evaluation of PEG₄-CPT against HeLa cells showed improved cellular uptake and enhanced cytotoxicity compared to free CPT. Thus, in this approach CPT acts in two ways: As the hydrophobic segment that enables self-assembly in water and as a potent anticancer agent. This concept of combining hydrophobic drugs and short star polymers shows great potential for efficient delivery of hydrophobic chemotrophic drugs as well as for drugs with inherent stability and pharmacokinetic barriers.