Background: Liposomes have been employed to improve pharmacokinetics and reduce side effects of drugs.
They can be functionalized with antibodies for targeted delivery. While the monoclonal antibody trastuzumab has been
employed in the therapy of HER2-positive breast cancer, the resistance developed during treatment has been reported.
Rapamycin could be used in combination with trastuzumab for improved therapeutic response.
Objective: In this study, we aimed to develop rapamycin-loaded liposomes and immunoliposomes with trastuzumab,
characterize them and evaluate their in vitro cytotoxicity.
Method: Formulations were prepared by the thin film hydration method and immunoliposome was conjugated to
antibody by covalent bond. Characterization involved particle size, polydispersity, zeta potential, encapsulation
efficiency, functionalization efficiency, DSC and FTIR assays. Cell studies were conducted through the MTT assay.
Results: SPC:Chol:DSPE-PEG formulation prepared at 1:10 drug to lipid ratio presented high encapsulation efficiency,
appropriate particle size, low polydispersity, negative zeta potential and colloidal stability. Rapamycin exhibited
intermolecular interactions with lipids and underwent crystallinity reduction. Rapamycin-loaded immunoliposomes
were prepared with high trastuzumab functionalization efficiency and antibody stability. Cytotoxicity studies showed
that the HER2-positive SK-BR-3 cell line was sensitive to trastuzumab, either as free drug or in the context of
immunoliposomes, and is more sensitive to rapamycin than the triple negative MDA-MB-231 cells. For MDA-MB-231,
the liposomal rapamycin was more cytotoxic than the free drug. Furthermore, the immunoliposomes showed potent
cytotoxicity against SK-BR-3 cells. Finally, rapamycin and trastuzumab exhibited in vitro synergistic effect, particularly
Conclusion: The formulation developed herein has potential for in vivo evaluation.