phenylalanine-methyl-ester and Ovarian-Neoplasms

Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70 nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics.

Topics: Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Cross-Linking Reagents; Doxorubicin; Drug Carriers; Drug Delivery Systems; Female; Gels; Humans; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; MCF-7 Cells; Mice; Nanoparticles; Ovarian Neoplasms; Particle Size; Phenylalanine; Polyethylene Glycols; Polyglutamic Acid; Polymers; Time Factors; Xenograft Model Antitumor Assays