Evaluation of Human Serum Albumin Nanoparticles for Rapamycin Delivery

Abstract

Rapamycin (RAP) is a macrolide antibiotic with potent immunomodulatory and anticancer properties, but its clinical use is hindered by poor solubility, chemical instability, and limited bioavailability. The aim of this study was the development of PEG-coated albumin nanoparticles for delivering rapamycin and maintaining its biological activity after encapsulation. Rapamycin-loaded albumin nanoparticles were prepared by desolvation of an aqueous solution of the protein with ethanol and subsequent coating with PEG 35,000. The resulting nanoparticles (NPA-RAP) displayed adequate physicochemical properties for intravenous delivery, including sizes within the tumor-targeting range (150–200 nm), low polydispersity (<0.2), and negative zeta potential (∼−30 mV). PEGylation and surface charge ensured short-term stability, while encapsulation efficiency exceeded 70%, with sustained biphasic release (40% over 24 h) well described by the Weibull model. In vitro, NPA-RAP showed cytotoxicity in MCF-7 breast cancer cells comparable to free rapamycin but with lower IC50 values. In Caenorhabditis elegans, NPA-RAP did not affect fat content but extended lifespan by ∼70%, outperforming free rapamycin. These results suggest that these nanoparticles can successfully transport rapamycin without causing detectable carrier-induced toxicity, highlighting its promise for further therapeutic assessment.