Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations

Abstract

Background Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. Results Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. Conclusions The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy. Graphic abstract

Comparative Colloidal Stability of Commercial Amphotericin B Nanoformulations Using Dynamic and Static Multiple Light Scattering Techniques

“…The flocculated nanoparticles were re-dispersed in the medium after shaking and mixing, and the average particle size and particle size distribution hardly changed in a short time, which led to false-positive results. 27 In addition, the method is limited by the concentration of nanoparticles: samples that are too thick or too thin will affect the accuracy of the determination results. 18 , 24 …”

“…The average particle size, size distribution, polydispersity index (PDI), and zeta potential of the reconstituted AmB nanoformulations were determined by dynamic light scattering (DLS) using a NICOMP 380 ZLS particle sizer (PSS NICOMP, Santa Barbara, CA, USA). 27 Each sample was diluted with 5% dextrose injection, as described above, transferred to a light scattering cell, and analyzed. The analyses were performed at a temperature of 25°C.…”

“…The in vitro colloidal stability of the reconstituted AmB nanoformulations at 4°C or 24°C was qualitatively determined for 24 h using a Turbiscan Tower (Formulaction, L’Union, France) using the static multiple light scattering (SMLS) technique. 26 , 27 The reconstituted AmB nanoformulations were appropriately diluted as described above and approximately 4 mL of each sample were individually placed in a cylindrical glass cell and stored in the Turbiscan Tower for 24 h at 4 or 24°C. The detection unit of Turbiscan Tower consists of a near-infrared light source (λ = 880 nm) and two synchronous transmission and backscattering detectors.…”

HSA-Binding Prodrugs-Based Nanoparticles Endowed with Chemo and Photo-Toxicity against Breast Cancer

“…Overall, these very preliminary data show that treatment with MAL -PTX 2 S@Pba tends to reduce lung metastases (number and weight), thus posing encouraging bases for future in vivo validation with higher/repeated treatment doses. Indeed, it is worth noticing that notwithstanding our experimental setup included an extremely low drugs dose, i.e., 8.16 mg/Kg PTX and 2.34 mg/Kg Pba, with respect to literature data ranging between 20 to 50 mg/Kg [ 54 ], still our new MAL -PTX 2 S@Pba NPs significantly reduced mammary tumor growth while displaying encouraging signal in curbing lungs metastasis growth.…”

Mechanochemical preparation of triptolide-loaded self-micelle solid dispersion with enhanced oral bioavailability and improved anti-tumor activity

“…Then, Na 2 GA&TP-UM and Na 2 GA&TP-BM at 200 ng/mL TP concentration were added to the 96-well plate every two days and followed by a 2-weeks’ observation. The major ( d max ) and minor ( d min ) diameters of each spheroid were measured, and the volume of 3D tumor sphere was calculated by using the following formula: V = (π × d max × d min )/6 (Ye et al., 2021 ).…”