Synthesis and characterization of phenylboronic acid-containing polymer for glucose-triggered drug delivery

Abstract

Thermo-, pH- and glucose-responsive polymeric nanoparticles are of great interest in developing a self-regulated drug delivery system. The novel core-shell nanoparticles were synthesized by self-assembly of a phenylboronic acid-based block copolymer poly-(N-isopropylacrylamide)-block-poly(3-acrylamidophenylboronic acid) (PNIPAM₁₃₆-b-PAPBA₁₆) and a fluorescent complex glucosamine-poly(N-isopropylacrylamide)/Eu(III) (GA-PNIPAM)/Eu(III) based on the cross-linking between PBA- and GA-containing blocks in this work. The nanoparticles can be tuned via thermo-induced collapse or glucose-induced swelling at appropriate pH and temperatures; they had an average kinetic radius was about 80nm, and which showed excellent fluorescence. MTT assays revealed the nanocarriers had no significant cytotoxic response of the micelle when it was observed in the cell line over the concentration range from 0.1 to 1000 μg/ml at any exposure times.

Keywords: 103 Composites; 301 Chemical syntheses / processing; 501 Chemical analyses; D-glucosamine (GA); Poly(N-isopropylacrylamide) (PNIPAM); poly(3-acrylamido- phenylboronic acid)(APBA); lower critical solution temperature(LCST).

Graphical abstract

Scheme 1

Schematic of the nanoparticles synthesis

Scheme 2

Synthesis of poly(3-acrylamidophenylboronic acid)-b-poly(N-isopropylacrylamide) (PNIPAM-b-PAPBA) via RAFT

Scheme 3

GA-PNIPAM synthesis by ATRP

Figure 1.

¹H NMR spectra of PNIPAM-b-PAPBA

Figure 2.

Fourier infrared transmittance spectrum (FT-IR) of PNIPAM-b-PAPBA

Figure 3.

Transmittance of PNIPAM-b-PAPBA with different molecular weights at λ = 500 nm and for pH = 7.4 and 9.3

Figure 4.

Scattered light intensity recorded for the aqueous mixture (pH = 7.4, T = 42°C)

Figure 5.

Intensity-average hydrodynamic radius distributions f(R_h) of complex micelles

Figure 6.

TEM images of self-assembly micelles (Scale bar 0.5 μm)

Figure 7.

Fluorescence spectra recorded for (GA-PNIPAM)/Eu(III) and complex micelles (excitation wavelength 355 nm)

Figure 8.

Transmittance for pH = 7.4 solutions of complex micelles

Figure 9.

Ph dependence of scattered intensity-average hydrodynamic radius <R_h> recorded for the aqueous mixture of complex micelles

Figure 10.

Glucose concentration dependence of scattered light intensity recorded for the aqueous mixture of complex micelles at pH = 7.4

Figure 11.

Viability of (a) the L-929 cells and (b) the MCF-7 cells incubated with the samples ((GA-PNIPAM)/Eu(III), (PNIPAM-b-PAPBA) and complex micelles), over a range of sample concentrations from 0.1 to 1000 μg/ml by MTT assay for 48 h