Solid lipid nanoparticles with docetaxel inside stop 4T1 mouse mammary cancer cells from developing tumors and spreading to the lungs


Vinod D. Usnale, Rohit D. Usnale, Ravi.R.More,  Dr.Jyotiram A Sawale, Dr.Reenu Yadav, Dr.Jitendra Malviya
IES Institute of Pharmacy,Bhopal (MP), India.


Background: The majority of breast cancer-related fatalities in women are caused by metastasis. Here, utilizing 4T1-bearing BALB/c mice, we examined the anti-tumor effects of solid lipid nanoparticles (SLN-DTX) when utilized in the treatment of metastatic breast cancers. Results: By employing high energy, solid lipid nanoparticles (SLNs) were created. To stabilize nanoparticle dispersion, Compritol 888 ATO was used as the lipid matrix and Pluronic F127 and Span 80 as the surfactants. For at least 120 days, the particles had a high level of stability. The SLNs have a 128 nm dispersion size, a 0.2 polydispersity index (PDI), and a negative zeta potential. SLNs had a regulated drug release profile, high docetaxel (DTX) entrapment efficiency (86%), and drug loading of 2%. After 24 hours of treatment, SLN-DTX's half-maximal inhibitory concentration (IC50) against 4T1 cells was more than 100 times lower than that of free DTX. SLNDTX was substantially more effectively absorbed into the cells during the cellular absorption test than free DTX. When comparing cells treated with SLN-DTX (73.7%) to cells treated with free DTX (23.0%), which thereafter caused apoptosis, the accumulation in the G2M phase was much higher in the former group of cells. According to TEM research, endocytosis is the mechanism by which SLN-DTX internalization occurs, and fluorescence microscopy demonstrated that DTX caused microtubule damage. Studies conducted in animals revealed that SLN-DTX had stronger anticancer effectiveness than free docetaxel by decreasing tumor volume (p 0.0001) and preventing spontaneous lung metastasis in mice with 4T1 tumors. Lung histological tests proved that SLNDTX therapy could stop tumor growth. When taken as a combination therapy, IL-6 serum levels, ki-67, and BCL-2 expression all demonstrated a strikingly significant reduction.