Paclitaxel-Loaded SCK Nanoparticles: An Investigation of Loading Capacity and Cell Killing Abilities <i>in Vitro</i>

Block copolymer nanoparticles having two different hydrodynamic diameters (120 nm vs 50 nm) and core diameters (60 nm vs 20 nm) with variable paclitaxel loading (5 to 20 wt % with respect to polymer weight, 4.4 μg/mL to 21.7 μg/mL paclitaxel concentrations in ultrapure water) were prepared for their <i>in vitro</i> cytotoxicity evaluation. Empty nanoparticles did not show any inherent cytotoxicity even at their highest concentration, whereas paclitaxel-loaded nanoparticles resulted in IC₅₀ values that were better than free paclitaxel at 2 h (0.021 μM vs 0.046 μM) incubation periods, and approximately equal to free paclitaxel at 72 h (0.004 μM vs 0.003 μM) continuous incubation. Confocal fluorescence microscopy images demonstrated that the drug-loaded nanoparticles internalized into KB cells within 2 h and released their payload, resulting in cytotoxicity as evident from the fragmented nuclei present. Functionalization of the nanoparticle surfaces with poly­(ethylene oxide) (2 kDa PEO, 5 PEO per block copolymer chain) did not affect the loading of paclitaxel or cell kill ability. No free paclitaxel was found in these nanoparticle formulations indicated by analytical assays

<i>In Vitro</i> Efficacy of Paclitaxel-Loaded Dual-Responsive Shell Cross-Linked Polymer Nanoparticles Having Orthogonally Degradable Disulfide Cross-Linked Corona and Polyester Core Domains

Paclitaxel-loaded shell cross-linked polymeric nanoparticles having an enzymatically and hydrolytically degradable poly­(lactic acid) core and a glutathione-responsive disulfide cross-linked poly­(oligoethylene glycol)-containing corona were constructed in aqueous solution and investigated for their stimuli-responsive release of the embedded therapeutics and <i>in vitro</i> cytotoxicity. Paclitaxel release from the nanoparticles in PBS buffer was accelerated in the presence of glutathione at both pH 5.5 and pH 7.4, reaching <i>ca</i>. 65% cumulative drug release after 8 d, whereas only <i>ca</i>. 50% and 35% extents of release were observed in the absence of glutathione at pH 5.5 and pH 7.4, respectively. Enzyme-catalyzed hydrolysis of the nanoparticle core resulted in the degradation of <i>ca</i>. 30% of the poly­(lactic acid) core to lactic acid within 12 h, with coincidently triggered paclitaxel release of <i>ca</i>. 37%, as opposed to only <i>ca</i>. 17% release from the uncatalyzed nanoparticles at pH 7.4. While empty nanoparticles did not show any inherent cytotoxicity at the highest tested concentrations, paclitaxel-loaded nanoparticles showed IC₅₀ values that were similar to those of free paclitaxel at 72 h incubation with KB cells and were more efficacious at <i>ca</i>. 3-fold lower IC₅₀ value (0.031 μM vs 0.085 μM) at 2 h of incubation. Against human ovarian adenocarcinoma cells, the paclitaxel-loaded nanoparticles exhibited a remarkable <i>ca</i>. 11-fold lower IC₅₀ than a Taxol-mimicking formulation (0.0007 μM vs 0.008 μM) at 72 h of incubation. These tunable dual-responsive degradable nanoparticles show great promise for delivery of paclitaxel to tumor tissues, given their superior <i>in vitro</i> efficacies compared to that of free paclitaxel and Taxol-mimicking formulations

<i>In Vitro</i> Efficacy of Paclitaxel-Loaded Dual-Responsive Shell Cross-Linked Polymer Nanoparticles Having Orthogonally Degradable Disulfide Cross-Linked Corona and Polyester Core Domains

Paclitaxel-loaded shell cross-linked polymeric nanoparticles having an enzymatically and hydrolytically degradable poly­(lactic acid) core and a glutathione-responsive disulfide cross-linked poly­(oligoethylene glycol)-containing corona were constructed in aqueous solution and investigated for their stimuli-responsive release of the embedded therapeutics and <i>in vitro</i> cytotoxicity. Paclitaxel release from the nanoparticles in PBS buffer was accelerated in the presence of glutathione at both pH 5.5 and pH 7.4, reaching <i>ca</i>. 65% cumulative drug release after 8 d, whereas only <i>ca</i>. 50% and 35% extents of release were observed in the absence of glutathione at pH 5.5 and pH 7.4, respectively. Enzyme-catalyzed hydrolysis of the nanoparticle core resulted in the degradation of <i>ca</i>. 30% of the poly­(lactic acid) core to lactic acid within 12 h, with coincidently triggered paclitaxel release of <i>ca</i>. 37%, as opposed to only <i>ca</i>. 17% release from the uncatalyzed nanoparticles at pH 7.4. While empty nanoparticles did not show any inherent cytotoxicity at the highest tested concentrations, paclitaxel-loaded nanoparticles showed IC₅₀ values that were similar to those of free paclitaxel at 72 h incubation with KB cells and were more efficacious at <i>ca</i>. 3-fold lower IC₅₀ value (0.031 μM vs 0.085 μM) at 2 h of incubation. Against human ovarian adenocarcinoma cells, the paclitaxel-loaded nanoparticles exhibited a remarkable <i>ca</i>. 11-fold lower IC₅₀ than a Taxol-mimicking formulation (0.0007 μM vs 0.008 μM) at 72 h of incubation. These tunable dual-responsive degradable nanoparticles show great promise for delivery of paclitaxel to tumor tissues, given their superior <i>in vitro</i> efficacies compared to that of free paclitaxel and Taxol-mimicking formulations