Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery

Abstract

The purpose of this study was to develop a novel lipid–polymer hybrid drug carrier comprised of folate (FA) modified lipid-shell and polymer-core nanoparticles (FLPNPs) for sustained, controlled, and targeted delivery of paclitaxel (PTX). The core-shell NPs consist of 1) a poly(ε-caprolactone) hydrophobic core based on self-assembly of poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL-PEG-PCL) amphiphilic copolymers, 2) a lipid monolayer formed with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N -[methoxy (polyethylene glycol)-2000] (DSPE-PEG2000), 3) a targeting ligand (FA) on the surface, and were prepared using a thin-film hydration and ultrasonic dispersion method. Transmission electron microscopy and dynamic light scattering analysis confirmed the coating of the lipid monolayer on the hydrophobic polymer core. Physicochemical characterizations of PTX-loaded FLPNPs, such as particle size and size distribution, zeta potential, morphology, drug loading content, encapsulation efficiency, and in vitro drug release, were also evaluated. Fluorescent microscopy proved the internalization efficiency and targeting ability of the folate conjugated on the lipid monolayer for the EMT6 cancer cells which overexpress folate receptor. In vitro cytotoxicity assay demonstrated that the cytotoxic effect of PTX-loaded FLPNPs was lower than that of Taxol ® , but higher than that of PTX-loaded LPNPs (without folate conjugation). In EMT6 breast tumor model, intratumoral administration of PTX-loaded FLPNPs showed similar antitumor efficacy but low toxicity compared to Taxol ® . More importantly, PTX-loaded FLPNPs showed greater tumor growth inhibition (65.78%) than the nontargeted PTX-loaded LPNPs (48.38%) ( P <0.05). These findings indicated that the PTX loaded-FLPNPs with mixed lipid monolayer shell and biodegradable polymer core would be a promising nanosized drug formulation for tumor-targeted therapy.

<p>Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy</p>

“…53 Some researches reported FA modified MPEG-PCL polymers encapsulating chemotherapeutic or hormonetherapeutic drugs such as doxorubicin, paclitaxel and tamoxifen in cancer therapy, which showed a good anti-tumor effect. [54][55][56] Another study introduced a Y-shaped FA-MPEG-PCL 2 copolymer with a particle size of 48.94 nm to improve the uptake of Cur in Hela and HepG2 cells. 57 Herein, we synthesized Cur-loading FA/MPEG-PCL micelles (FA/Nano-Cur) with an average size of 30.47 nm for vein injection, which was expected to improve the bioavailability of Cur.…”

<p>Hyaluronic Acid Capped, Irinotecan and Gene Co-Loaded Lipid-Polymer Hybrid Nanocarrier-Based Combination Therapy Platform for Colorectal Cancer</p>

“…The particle size, polydispersity, and zeta potential of the LPNs were determined by dynamic light scattering (DLS) using a NanoZS Zetasizer (Malvern Instruments Ltd., Malvern, UK). 24 TEM pictures are Morphologies and size of NI/HA-DDP-PNPs and NI/HA-DDP-LPNs were recorded by a transmission electron microscopy.…”

<p>Targeted Therapy for Hepatocellular Carcinoma: Co-Delivery of Sorafenib and Curcumin Using Lactosylated pH-Responsive Nanoparticles</p>

“…Compared with the uniform particles of SFN/CCM-NPs, LAC-SFN/CCM-NPs are spherical particles with light coats on the surface, which could be the evidence of the lactose moiety presented on the surface of the nanoparticles. 50 The size of the LAC-SFN/CCM-NPs was 115.5 ± 3.6 nm, with a PDI of 0.183 ± 0.009. PDI was applied to determine the size range and size distribution of the nanoparticles.…”