Abstract
Polymer-based nanoparticles have been largely investigated in the cancer therapy field for their features to generate colloidal delivery systems of hydrophobic drugs to improve drug stability, specific delivery and reduce toxicity. In particular, nanoparticles surface functionalized with hyaluronic acid have been widely employed for their active tumor-targeting efficiency. Furthermore, the control of the physicochemical properties as well as high drug encapsulation efficiency, yield and batch-to-batch reproducibility of nanoparticles obtained by means of microfluidics, pave the way to overcome the drawbacks related to the fabrication of NPs obtained via traditional bulk methods and consequently increase cancer cell killing effect. For these reasons, we here investigated the effects of process parameters on the preparation and optimization of poly(lactic-co-glycolic acid)-poloxamers nanoparticle formulations (PLGA/PF68+PF127 NPs) decorated with HA (HA-based NPs) by using microfluidics for intravenous delivery of a model chemotherapeutic agent, irinotecan (IRIN). The study on the aggregation behavior and morphology of NPs were investigated by Dynamic Light Scattering (DLS), Electrophoretic Light Scattering (ELS), Transmission Electron Microscopy (TEM) and Differential Scanning Calorimetry (DSC). Our results revealed that by increasing the polymer weight fractions of organic and water phases the size, the NP yield, and the drug encapsulation efficiency of NPs are increased. Furthermore, by increasing the flow rate ratios from 0.05 to 0.3, a raise of dH from ∼85.6 to ∼176.4, for PLGA/PP NPs, and from ∼101.6 to ∼283.3 for HA/PLGA/PP is detected. The optimized HA-based NP formulation showed a spherical morphology, with a core-shell structure, small hydrodynamic diameter (dH∼120 nm), uniform size distribution (PDI<0.06) and high: i) drug loading (DL∼22.7%), ii) drug encapsulation efficiency (DEE∼87.8%) and iii) yield (92.4%). Moreover, the in vitro IRIN kinetic release and stability of IRIN-loaded HA-based NPs were evaluated showing the complete release in 15 days. Thus, this study highlighted a microfluidic method to fabricate IRIN-loaded HA-based NPs without any chemical modifications to provide novel understanding of the effect of process parameters, by varying the polymer weight fractions of both organic and water phases and flow rate ratio, on the physicochemical properties and consequently on nanoparticle formulation qualities for cancer therapy applications.
Published Version
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