Fine Tuning Micellar Core-Forming Block of Poly(ethylene glycol)-block-poly(ε-caprolactone) Amphiphilic Copolymers Based on Chemical Modification for the Solubilization and Delivery of Doxorubicin

Abstract

This study aimed to optimize poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL)-based amphiphilic block copolymers for achieving a better micellar drug delivery system (DDS) with improved solubilization and delivery of doxorubicin (DOX). First, the Flory-Huggins interaction parameters between DOX and the core-forming segments [i.e., poly(ε-caprolactone) (PCL) and poly[(ε-caprolactone-co-γ-(carbamic acid benzyl ester)-ε-caprolactone] (P(CL-co-CABCL))] was calculated to assess the drug-polymer compatibility. The results indicated a better compatibility between DOX and P(CL-co-CABCL) than that between DOX and PCL, motivating the synthesis of monomethoxy-poly(ethylene glycol)-b-poly[(ε-caprolactone-co-γ-(carbamic acid benzyl ester)-ε-caprolactone] (mPEG-b-P(CL-co-CABCL)) block copolymer. Second, two novel block copolymers of mPEG-b-P(CL-co-CABCL) with different compositions were prepared via ring-opening polymerization of CL and CABCL using mPEG as a macroinitiator and characterized by (1)H NMR, FT-IR, GPC, WAXD, and DSC techniques. It was found that the introduction of CABCL decreased the crystallinity of mPEG-b-PCL copolymer. Micellar formation of the copolymers in aqueous solution was investigated with fluorescence spectroscopy, DLS and TEM. mPEG-b-P(CL-co-CABCL) copolymers had a lower critical micelle concentration (CMC) than mPEG-b-PCL and subsequently led to an improved stability of prepared micelles. Furthermore, both higher loading capacity and slower in vitro release of DOX were observed for micelles of copolymers with increased content of CABCL, attributed to both improved drug-core compatibility and favorable amorphous core structure. Meanwhile, DOX-loaded micelles facilitated better uptake of DOX by HepG2 cells and were mainly retained in the cytosol, whereas free DOX accumulated more in the nuclei. However, possibly because of the slower intracellular release of DOX, DOX-loaded micelles were less potent in inhibiting cell proliferation than free DOX in vitro. Taken together, the introduction of CABCL in the core-forming block of mPEG-b-PCL resulted in micelles with superior properties, which hold great promise for drug delivery applications.

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

“…51 These two melting events suggest the existence of two distinct crystalline domains in the miktoarm polymer. 30 CoQ10/PEG2-PCL3.8-TPPBr physical mixture shows the same characteristic melting peaks for both CoQ10 and PEG2-PCL3.8-TPPBr copolymer ( Figure 4B). In contrast, the DSC thermogram of the lyophilized CoQ10/PEG2-PCL3.8-TPPBr micelle shows a bimodal endothermic peak at 45.40 and 48.31°C corresponding, respectively, to the melting of PEG and CoQ10 ( Figure 4B).…”

“…Several recent studies have shown that polymer−drug compatibility is a key factor in determining the performance of polymeric micelle as drug delivery systems where high compatibility results in higher drug solubility, loading capacity, and controlled drug release. 30,31,45,46 To explain the exceptionally high CoQ10 loading into PEG2-PCL3.8-TPPBr micelles, we used the Flory−Huggins interaction parameter (χ sm ) to estimate the CoQ10-PCL compatibility, because it has been shown to be a good indicator of polymer−drug compatibility. 31,47 The Hansen partial solubility parameters for CoQ10, nimodipine, and PCL were obtained based on the group contribution method using the Molecular Modeling Pro software (Table 1, Supporting Information).…”

Structure–property relationship of pH‐sensitive (PCL)2(PDEA‐b‐PPEGMA)2 micelles: Experiment and DPD simulation

“…In the case of the nonpolar components or components without specific interactions (e.g., hydrogen bonding), and if the excess entropy and excess volume can be ignored, v ij can be obtained from the solubility parameters 39,40 …”

Folate‐Conjugated Poly(N‐(2‐hydroxypropyl) methacrylamide)‐block‐Poly(benzyl methacrylate): Synthesis, Self‐Assembly, and Drug Release

“…[ 27 ] The introduction of a benzyl ester group to poly(ethylene glycol)-blockpoly( ε -caprolactone) was also achieved, which showed a delayed release of DOX as a result of π -π stacking. [ 28 ] Herein, we report a new synthesis of well-defi ned poly( N -(2-hydroxypropyl)methacrylamide)-block -poly(benzyl methacrylate) (PHPMA-b -PBnMA) using the RAFT polymerization without post-polymerization modifi cation. The terminal dithiobenzoate group of the polymer was converted into the corresponding carboxylic acid by a one pot reaction with NaBH 4 /acrylic acid, which readily underwent a conjugation reaction with aminated-folic acid (FA-NH 2 ).…”