Lipid- and TPGS-Based Core–Shell-Type Nanocapsules Endowed with High Paclitaxel Loading and Enhanced Anticancer Potential

The current study elucidates the improved drug loading of paclitaxel (PTX) in lipid- and d-α-tocopheryl polyethylene glycol succinate (TPGS)–based core–shell-type lipid nanocapsules (PTX-TPGS-LNC) for augmenting the therapeutic efficacy and curbing the toxicity. PTX-TPGS-LNCs were formulated by empl...
Ausführliche Beschreibung

The current study elucidates the improved drug loading of paclitaxel (PTX) in lipid- and d-α-tocopheryl polyethylene glycol succinate (TPGS)–based core–shell-type lipid nanocapsules (PTX-TPGS-LNC) for augmenting the therapeutic efficacy and curbing the toxicity. PTX-TPGS-LNCs were formulated by employing anti-solvent precipitation technique and displayed a particle size of 162.1 ± 4.70 nm and % practical drug loading of 15.04 ± 2.44%. Electron microscopy revealed that PTX-TPGS-LNCs have spherical morphology and the inner core was surrounded by a relatively lighter region, i.e., layer of lipids and TPGS. The nature of loaded PTX inside the PTX-TPGS-LNC was also confirmed using DSC and PXRD analysis. The in vitro release study showed biphasic and sustained release pattern of PTX from PTX-TPGS-LNC and it showed ~ threefold higher PTX uptake in MCF-7 cell line in comparison to free PTX. Moreover, it was apparent from the cytotoxicity assay that PTX-TPGS-LNC displayed higher cytotoxicity in MCF-7 cells and revealed ~ 2.92-fold decrease in $ IC_{50} $ value as against free PTX when incubated for 72 h. The apoptotic index in case of PTX-TPGS-LNC was ~ twofold higher than free PTX. The pharmacokinetic profile of PTX-TPGS-LNC revealed a ~ 3.18-fold increase in t1/2 and a ~ 2.62-fold higher $ AUC_{(0→∞)} $ compared to $ Intaxel^{®} $. Finally, treatment with PTX-TPGS-LNC demonstrated significant lowering in the % tumor burden and serum toxicity markers compared to marketed formulation $ Intaxel^{®} $. Thus, the lipid- and TPGS-based core–shell-type LNC with high PTX loading can advance the existing standards of therapy for overshadowing cancer. Graphical abstract Ausführliche Beschreibung