Dual Loading of Doxorubicin and Magnetic Iron Oxide into PLA‐TPGS Nanoparticles: Design, in vitro Drug Release Kinetics, and Biological Effects on Cancer Cells

Abstract

The multifunctional nano drug delivery system (MNDDS) has much revolutionized in cancer treatment, aiming to eliminate many disadvantages of conventional formulations. This paper herein proposes and demonstrates MNDDS inspired by poly(lactide)‐tocopheryl polyethylene glycol succinate (PLA‐TPGS) copolymer co‐loaded Doxorubicin and magnetic iron oxide nanoparticles (MIONs) with a 1 : 1 (w/w) optimal ratio. In vitro drug release kinetics of Doxorubicin from this nanosystem fitted best to the Weibull kinetic model and can be described by the classical Fickian diffusion mechanism under acidic pH conditions. The combination of MIONs and Doxorubicin in the PLA‐TPGS copolymer has maintained the fluorescence properties of Doxorubicin and good cell penetration, especially inside the nucleus and its vicinity. Moreover, different cell cycle profiles were observed in HeLa cell lines treated with MNDDSs.

Near‐Infrared Emission‐Cyanine 5.5 and Doxorubicin Loaded Magnetite Nanoparticles for Dual In Vivo Magnetic Resonance and Biodistribution Imaging

“…[41,42] In the third stage, the weight loss was about 19.19 wt% in the range of 450-500 °C, which corresponds to the thermal decomposition of TPGS residues of the copolymer corresponding to the exothermic peak at 447.5 °C. [43,44] As a result, the weight loss of the PLA-TPGS-Fe 3 O 4 nanoparticles was 33.81 wt%, showing that the PLA-TPGS content of the corresponding nanocarrier was fairly consistent with the feeding ratio. By comparing the decomposition profiles of PLA-TPGS-Fe 3 O 4 systems, the higher weight-loss percentage in the PLA-TPGS-Fe 3 O 4 -Cyanine 5.5 and PLA-TPGS-Fe 3 O 4 -Cyanine 5.5-Dox samples proves once again that the content of Cyanine 5.5 and Dox was 1.25 % and 6.47 %, respectively.…”

“…It is due to the solvation shell of nanoparticles and several physicochemical approximations in the final calculation of the hydrodynamic diameters using DLS measurements as described in previous publications. [54] The size of the nanosystem gradually increases with storage time, reaching 128.0 � 3.5 nm and 188.0 � 3.8 nm for the PLA-TPGS-Fe 3 O 4 -Cyanine 5.5, and PLA-TPGS-Fe 3 O 4 -Cyanine 5.5-Dox NPs after 12 months, respectively. This might be because of the cluster formation in the dispersion and leading to a slight increase in the geometrically mass-averaged diameter.…”

“…This decreased M s value was also reported in other publications. [54,75,76] In addition, the very low measured coercivity values (Hc) of Fe 3 O 4 NPs, PLA-TPGS-Fe 3 O 4 -Cyanine 5.5, and PLA-TPGS-Fe 3 O 4 -Cyanine 5.5-Dox NPs of 5.2, 6.8, and 5.6 Oe, respectively, imply the superparamagnetic properties of the as-synthesized nanoparticles at room temperature. [77,78] Based on the magnetic and optical characteristics of the nanoparticles, it can be inferred that the PLA-TPGS-Fe 3 O 4 -Cyanine 5.5-Dox nanoparticles exhibit high fluorescence emission with superparamagnetic properties, suggesting their potential applications in in vivo biomedicine.…”

“…For efficient drug delivery to tumor extracellular matrix and intracellular cells and to avoid premature release, the drug kinetics and release mechanisms of doxorubicin and Fe 3 O 4 NPs co-loaded on PLA-TPGA copolymer have been reported in our previous study. [54] Here, we attached Cyanine 5.5 to the synthesized PLA-TPGS-Fe 3 O 4 -Cyanine 5.5-Dox nanosystem to formulate a novel theranostic agent with multimodal imaging and effective drug delivery ability. In this study, when incorporating Cyanine 5.5, the Dox encapsulating efficiency of the PLA-TPGS-Fe 3 O 4 -Cyanine 5.5-Dox NPs was calculated to be 84.7 % at the feed concentration of 250 μg.mL À 1 , and the Dox loading content was calculated to be 6.67 % by weight of the nanosystem.…”

“…[81,82] Under acidic conditions, Dox was released from the PLA-TPGS copolymer according to the Weibull kinetic model following the classical Fickian diffusion mechanism. [54] The Dox release of the PLA-TPGS-Fe 3 O 4 -Cyanine 5.5-Dox nanosystem was slower than the previous study without Cyanine 5.5 in both pH 5.0 and 7.4 conditions. [54] This may be due to the lipophilicity and negative charge of Cyanine 5.5 which partially interfered with Dox release through the molecular interaction between Doxorubicin and Cyanine 5.5 co-encapsulated by PLA-TPGS copolymer.…”