Synthesis and Characterization of Hybrid Polymer/Lipid Expansile Nanoparticles: Imparting Surface Functionality for Targeting and Stability

Abstract

The size, drug loading, drug release kinetics, localization, biodistribution, and stability of a given polymeric nanoparticle (NP) system depend on the composition of the NP core as well as its surface properties. In this study, novel, pH-responsive, and lipid-coated NPs, which expand in size from a diameter of approximately 100 to 1000 nm in the presence of a mildly acidic pH environment, are synthesized and characterized. Specifically, a combined miniemulsion and free-radical polymerization method is used to prepare the NPs in the presence of PEGylated lipids. These PEGylated-lipid expansile NPs (PEG-L-eNPs) combine the swelling behavior of the polymeric core of expansile NPs with the improved colloidal stability and surface functionality of PEGylated liposomes. The surface functionality of PEG-L-eNPs allows for the incorporation of folic acid (FA) and folate receptor-targeting. The resulting hybrid polymer/lipid nanocarriers, FA-PEG-L-eNPs, exhibit greater in vitro uptake and potency when loaded with paclitaxel compared to nontargeted PEG-L-eNPs.

Evaluation of Expansile Nanoparticle Tumor Localization and Efficacy in a Cancer Stem Cell-Derived Model of Pancreatic Peritoneal Carcinomatosis

“…We have previously shown that by modifying eNP -targeted) the rates of particle internalization can be tuned and, in particular, selectively increased in tumor-cell subtypes that overexpress the folate receptor [40]. However, surface modification can interfere with the pH functionality of the system and, for this reason, it was not employed in the current study [40].…”

“…Surface charge is one of the factors that impacts nanoparticle internalization within cells (in addition to particle size, shape and stiffness), as has been described in a number of papers and reviews [35][36][37][38][39]. We have previously shown that by modifying eNP -targeted) the rates of particle internalization can be tuned and, in particular, selectively increased in tumor-cell subtypes that overexpress the folate receptor [40]. However, surface modification can interfere with the pH functionality of the system and, for this reason, it was not employed in the current study [40].…”

Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors

“…Fourth, due to the pH-responsive swelling functionality, where HFR-eNPs expand from ~30 to ~500 nm—described in detail in ref 45 and in refs 29, 31, 36, 42, and 46—the pH of the local microenvironment may play a role in the specificity of the HFR-eNPs for tumors. To determine the relationship of eNP localization and low-pH tumor microenvironments, we immunostained tissues for (1) HIF1 α as an indicator of cellular hypoxia and hypoxia-associated low pH and (2) lactate dehydrogenase-A (LDH-A) expression as an indicator of lowpH tumor microenvironments from the production of lactic acid.…”

Treatment of experimental autoimmune uveoretinitis with intravitreal injection of infliximab encapsulated in liposomes

“…The stability is an important factor for successful application of liposomes as drug carrier 32. It can be improved by adding PEG to the surface of the liposomes because PEG constitutes a hydrophilic layer surrounding the vesicles which may protect the liposomes from degradation or accelerated leakage 33 34.…”