(636i) Synergistic Assembly of Peptide Amphiphiles for Encapsulation of Camptothecin

Peptide amphiphiles(PAs) are a versatile class of self-assembling materials consisting of hydrophobic and hydrophilic segments which form supramolecular nanostructures like fibers, micelles and tubes. Self-assembly process involves a diverse range of forces like electrostatic interaction, hydrogen bonding, hydrophobic interaction and van der Waals force. The balance between these forces is dictated by molecular design to fabricate ordered structures with a high degree of atomic precision, regulated morphology and size. The hydrophobic region of the PAs form a hydrophobic core and the hydrophilic region projects outward on the surface of PA. This hydrophobic core can be exploited as a carrier for hydrophobic drugs.

In this study, camptothecin is chosen as the model hydrophobic drug for encapsulation. Currently, it is being used in cancer chemotherapy in the form of its analogues for the treatment of lung, colon and prostate cancer. However, its analogues impose certain clinical limitations as they cause an inactivation of its lactone form in blood and require prolonged infusions to prevent reversal of DNA cleavage. These limitations can be overcome by encapsulation of camptothecin in PAs by a co-assembly method. Two oppositely charged PAs sequences mutually screen the charges of each other in a synergistic manner to form hybrid drug encapsulated nanofibers. This novel method of encapsulation negates the use of external factors like pH, temperature and ions to bring about the self- assembly process and can also be used to design bifunctional nanofibers. Studies reveal that camptothecin was effectively encapsulated into the PAs fibers by a combination of hydrophobic and electrostatic interaction. Circular dichroism spectroscopy studies on the PAs-drug complexes demonstrate that the PAs retain their secondary structure and functionality when bound to the drug. The drug camptothecin was also found to exist in its active lactone form after encapsulation inside the PAs. In vitro drug release and cell studies were also performed to evaluate the controlled release and antitumor activity of camptothecin encapsulated in PAs. Overall, this PAs-drug system improves the bioavailability and cellular uptake of hydrophobic drugs in an aqueous environment due to their high aspect ratio.