Camptothecin (CPT) is a naturally occurring cytotoxic alkaloid having a broad spectrum of antitumor activity against several solid tumors. Unfortunately, CPT possesses low bioavailability and severe side effects as well as low encapsulation efficiency (<5%).
We propose to develop a novel drug delivery prototype based on amphiphilic bio-conjugates of hydrophilic, short multi-armed polymer (PEG4) and 2-3 CPT molecules that play a dual role: as the hydrophobic segment that enables self-assembly in water and as an anti-cancer agent. PEG4-CPT self-assembled in water into stable spherical nano-structures with a mean diameter around 200 nm, the formed particles were found to be in the appropriate size to obtain an enhanced permeability and retention (EPR) effect. The biological evaluation of the conjugates against Hela cells, showed an improved cellular uptake and enhanced cytotoxicity comparing to the free CPT.
The in-vitro release of the drug showed a preferable sustained release profile. Thus, this system's properties suggest a new concept for the delivery of the chemotherapeutic drug CPT and can be implemented with other hydrophobic drugs.