Lactoferrin nanoparticle mediated targeted delivery of 5-fluorouracil for enhanced therapeutic efficacy

Malignant melanoma is an aggressive form of skin cancer with high mortality rates. Common treatments for malignant melanoma involve a combination of radiotherapy and chemotherapy with fluorouracil (5 FU). A major challenge with melanoma treatment is active resistance to chemotherapeutic drugs. Superior treatment outcome lies on balance involving optimum therapeutic doses and the side effects associated with dose escalation. The study aimed to efficiently entrap 5-FU in lactoferrin nanoparticles (LfNPs) in an attempt to enhance its therapeutic efficacy. 5-FU loaded lactoferrin nanoparticles (5-FU-LfNPs) were prepared by sol-oil method with a narrow size distribution of 150 +/- 20 nm 5-FU-LfNPs exhibits high encapsulation efficiency (64 +/- 2.3%) and increased storage stability at 4 degrees C. Competitive ligand binding and lysosomal colocalization studies suggested a receptor mediated uptake for LfNPs internalization in B16F10 cells. Moreover, 5-FU-LfNPs show a pH dependent drug release similar to endosomal pH (pH 5 and 6). In addition compared to free 5-FU, 5-FU- LfNPs showed a higher intracellular uptake, prolonged retention and improved cytotoxicity (2.7-fold) in melanoma cells (B16F10). To conclude, LfNPs represent a superior nano-carrier for the targeted delivery of 5-FU in melanoma cells intended for the efficient treatment of melanoma though detailed in vivo investigations are warranted. (C) 2016 Elsevier B.V. All rights reserved.