Doxorubicin-loaded, pH-sensitive Albumin Nanoparticles for Lung Cancer Cell Targeting

In recent decades, scientific and medical communities have continuously sought new methods and chemistries to improve the treatment of cancer. Among many types of nanoparticles considered as carriers for drug delivery, the protein ones count among the safest. The present study aimed to investigate the physicochemical and biological effects of the supplementation of albumin nanoparticles with doxorubicin (DOX). DOX was co-precipitated with albumin in a desolvation process and entrapped inside the cross-linked albumin nanoparticles, where it disrupted the protein structure at various levels: (a) it reduced the particle size distribution homogeneity; (b) it extended the peptide bond length; (c) it lowered the thermal stability of albumin; (d) it lowered the crystallinity of the protein. Physicochemical mechanisms underlying these changes are discussed. The drug release was incomplete under the physiological conditions, but the nanoparticles fully released their chemotherapeutic payload when pH was decreased by a single unit from the physiological value. Because the extracellular pH of tumors is usually by a single pH unit lower than that of healthy tissues, this environmentally responsive drug delivery system composed of albumin nanoparticles may be applicable in the targeting of cancer cells. In vitro assays against human lung cancer cells demonstrated that DOX released from albumin nanoparticles had a four times higher apoptotic activity than the equivalent concentration of free DOX. The ability of albumin to prevent the agglomeration of partially hydrophobic DOX and release it at a sustained, zero-order rate over the first 12 h of incubation, with no burst effect, explains this ability to augment the activity of DOX against the lung cancer cells.