Vitamin E-Oligo(methyl diglycol l-glutamate) as a Biocompatible and Functional Surfactant for Facile Preparation of Active Tumor-Targeting PLGA Nanoparticles

Abstract

Poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles have attracted an enormous interest for controlled drug delivery. Their clinical applications are, however, partly hindered by lack of biocompatible, biodegradable and functional surfactants. Here, we designed and developed a novel biocompatible surfactant based on amphiphilic vitamin E-oligo(methyl diglycol l-glutamate) (VEOEG) for facile fabrication of robust and tumor-targeting PLGA-based nanomedicines. VEOEG was prepared with controlled Mn of 1.7-2.6 kg/mol and low molecular weight distribution (Đ = 1.04-1.16) via polymerization of methyl diglycol l-glutamate N-carboxyanhydride using vitamin E-ethylenediamine derivative (VE-NH2) as an initiator. VEOEG had a hydrophile-lipophile balance data of 13.8-16.1 and critical micellar concentration of 189.3-203.8 mg/L depending on lengths of oligopeptide. Using VEOEG as a surfactant, PLGA nanoparticles could be obtained via nanoprecipitation method with a small and uniform hydrodynamic size of 135 nm and positive surface charge of +26.6 mV, in accordance with presence of amino groups at the surface. The resulting PLGA nanoparticles could be readily coated with hyaluronic acid (HA) to form highly stable, small-sized (143 nm), monodisperse, and negatively charged nanoparticles (HA-PLGA NPs). Notably, paclitaxel-loaded HA-PLGA NPs (PTX-HA-PLGA NPs) exhibited better antitumor effects in CD44-positive MCF-7 breast tumor cells than Taxol (a clinical paclitaxel formulation). The in vivo pharmacokinetics assay in nude mice displayed that PTX-HA-PLGA NPs possessed a long plasma half-life of 3.14 h. The in vivo biodistribution studies revealed that PTX-HA-PLGA NPs had a high tumor PTX level of 8.4% ID/g, about 6 times better than that of Taxol. Interestingly, therapeutic studies showed that PTX-HA-PLGA NPs caused significantly more effective tumor growth inhibition, better survival rate and lower adverse effect than Taxol. VEOEG has emerged as a versatile and functional surfactant for the fabrication of advanced anticancer nanomedicines.

Chemical modifications of nucleic acid drugs and their delivery systems for gene‐based therapy

“…Amphiphilic vitE-modified oligonucleotide has a large surface area due to the hydrophobic vitE head and the hydrophilic tail portion of oligonucleotides. 109 VitE-modified oligonucleotide can possible interact with receptor proteins on cell surface for cell type specific capture and delivery. 110,111 The hydrophobic tocopherol of modified ASOs may bind to membranal intracellular organelles or intracellular proteins and assist the entrance of ASOs to cells.…”

“…vitE modification has been demonstrated to improve gene delivery of nucleic acid drugs in vitro and in vivo, similar to cholesterol modification. Amphiphilic vitE‐modified oligonucleotide has a large surface area due to the hydrophobic vitE head and the hydrophilic tail portion of oligonucleotides . VitE‐modified oligonucleotide can possible interact with receptor proteins on cell surface for cell type specific capture and delivery …”

Micelles Formed by Polypeptide Containing Polymers Synthesized Via N-Carboxy Anhydrides and Their Application for Cancer Treatment

“…In 2016 Wu et al [57] presented the synthesis of an innovative biocompatible surfactant based on Vitamin E-Oligo(methyl diglycol L-glutamate) (VEOEG). The synthesis of the polymer involved two steps.…”

Coating‐Sheddable CD44‐Targeted Poly(d,l‐lactide‐co‐glycolide) Nanomedicines Fabricated by Using Photoclick‐Crosslinkable Surfactant

“…Covalent conjugation of targeting ligands affording high stability and facile scale‐up holds great potential on surface coating of PLGA NPs. We recently prepared hyaluronic acid (HA)‐coated PLGA NPs using amine‐terminated vitamin E‐oligo(methyl diglycol l ‐glutamate) as a surfactant followed by absorbing and chemical conjugation with HA via amidation reaction . Interestingly, these HA covalently coated PLGA NPs were highly stable and showed good targetability to human A549 lung and MCF‐7 breast tumors in vivo.…”