Poly(ethyleneglycol)‑<i>b</i>‑Poly(ε-caprolactone-<i>co</i>-γ-hydroxyl-ε- caprolactone) Bearing Pendant Hydroxyl Groups as Nanocarriers for Doxorubicin Delivery
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Abstract
A novel biodegradable amphiphilic diblock copolymer methoxy
poly(ethylene
glycol)-<i>b</i>-poly(ε-caprolactone-<i>co-γ</i>-hydroxyl-ε-caprolactone) (mPEG-<i>b</i>-P(CL-<i>co</i>-HCL)) bearing pendant hydroxyl groups on the PCL block
was prepared. The hydroxyl groups were formed through the reduction
of ketones by sodium borohydride without protection and deprotection.
The obtained polymers were well characterized by <sup>1</sup>H NMR,
Fourier transform infrared (FT-IR), gel permeation chromatography
(GPC), differential scanning calorimetry (DSC), X-ray diffraction
(XRD), and contact angle measurement. mPEG-<i>b</i>-P(CL-<i>co</i>-HCL) could self-assemble into stable nanoparticles (NPs)
with critical micellar concentrations (CMC) of 6.3 <b></b>×
10<sup>–4</sup> ∼ 8.1 <b> × </b> 10<sup>–4</sup> mg/mL. The NPs prepared from mPEG-<i>b</i>-P(CL-<i>co</i>-HCL) were spherical in shape with diameters about 100
to 140 nm. The hydrophobic doxorubicin (DOX) was chosen as a drug
model and successfully encapsulated into the NPs. The encapsulation
efficiency and release kinetics of DOX were investigated. The results
indicated that the introduction of hydroxyl groups onto the core-forming
block could decrease the hydrophobicity of copolymers, thus improving
the storage stability of NPs in aqueous solution. Moreover, higher
loading capacity and slower <i>in vitro</i> release of DOX
were observed, which was due to the hydrogen-bonding formation between
DOX and hydroxyl groups. Meanwhile, the MTT assay demonstrated that
the blank NPs were biocompatible to HepG2 cell,s while free DOX and
DOX-loaded NPs showed significant cytotoxicity against the cells.
Moreover, Compared to the free DOX, the DOX-loaded NPs were more efficiently
internalized by HepG2 cells. In sum, the introduction of hydroxyl
groups on the polyester block in mPEG-<i>b</i>-P(CL-<i>co</i>-HCL) exhibited great potentials for modifications in
the stability, drug solubilization, and release properties of NPs