Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity

Abstract

to an improvement in the loading capacities of DOPC-based liposomes only. Up to 3.6-fold 11 decrease in drug loading was observed after liposome purification, likely due to the loss of 12 adsorbed and loosely entrapped DTX in the SEC column. Our in vitro toxicity results in PC3 13 monolayer showed that non-purified, DTX-loaded DOPC:Chol liposomes were initially (24 h) 14 more potent than the purified ones, due to the fast action of the surface-adsorbed drug. 15However, we hypothesize that over time (48 and 72 h) the purified, DTX-loaded DOPC:Chol 16 liposomes became more toxic due to high intracellular release of encapsulated DTX. Finally, 17 our cytotoxicity results in PC3 spheroids showed the superior activity of DTX-loaded liposomes 18 compared to free DTX, which could overcome the DTX poor tissue penetration, drug 19 resistance, and improve its therapeutic efficacy following systemic administration. 20 21

Optimization of Docetaxel Loading Conditions in Liposomes: proposing potential products for metastatic breast carcinoma chemotherapy

“…The results of weight monitoring indicated no significant loss of mouse body weight over time. Since body weight loss could be used as a sign of toxicity 52 , these results confirm that there is an relatively safe profile in the mice at the test dose for in vivo administration ( Fig. 4A upper and lower).…”

A Critical Review of Properties and Analytical Methods for the Determination of Docetaxel in Biological and Pharmaceutical Matrices

“…[51] Several liposomal characteristics are important for DTX delivery and the composition plays a central role, which is demonstrated in several reports in the literature. [52][53][54][55] For instance, Pereira et al [56] evaluated the effect of different lipids, DOPC, DPPC, and DSPC, on both the purification of DTX-loaded liposomes and cytotoxicity on prostate cancer (PC3) spheroids. The results showed that the use of DOPC, the only unsaturated lipid, caused higher loading compared to more rigid liposomes, prepared with the saturated lipids DPPC and DSPC.…”

Targeting prostate cancer cells with hybrid elastin-like polypeptide/liposome nanoparticles

“…This may be caused by interactions between hydrophobic tails of DSPE-PEG and phospholipids occupying potential drug-loading areas. 35,44 The encapsulation rates were sufficient to deliver equivalents of 40 and 80 µg/mL of DTX into PC-3 cell cultures. Liposome stocks were diluted in PBS to obtain 400 µg/mL of DTX, followed by a subsequent 1:10 or 1:5 dilution into RPMI medium to achieve final concentrations of 40 and 80 µg/mL, respectively.…”

“…34,35 Freshly prepared DTX-loaded liposomes or polypeptide/liposome nanoparticles were diluted into release buffer at a final polypeptide concentration of 25 µM and a liposome to polypeptide ratio of 1:10 (v/v). Final volumes of 550 µL were placed into a rinsed dialysis tubing cellulose membrane with 1.4 kDa molecular weight cutoff.…”