A facile strategy to fabricate glucose-responsive vesicles via a template of thermo-sensitive micelles

Abstract

A facile strategy toward the construction of glucose-responsive polymer vesicles at physiological pH is reported. A thermo-sensitive phenylboronic acid (PBA)-containing block copolymer PNIPAM-b-P(Aspco-AspPBA) was self-assembled into core-shell (CS) micelles with a PNIPAM core and a P(Asp-co-AspPBA) shell above the LCST of PNIPAM. The addition of a glucosamine (GA)-containing block copolymer PEG-b-P(Asp-co-AspGA) resulted in the formation of core-shell-corona (CSC) complex micelles because of the crosslinking between PBA-and GA-containing blocks. Polymer vesicles with a swollen PNIPAM core, a cross-linked P(Asp-co-AspPBA)/P(Asp-co-AspGA) vesicular membrane, and a PEG corona were obtained simply by storing the CSC complex micelles below the LCST of PNIPAM. A combination of transmission electron microscopy (TEM) and dynamic light scattering (DLS) in terms of the variations of hydrodynamic diameter (D h ) and light scattering intensity (LSI) was applied to characterize the polymer vesicles in PBS solution with glucose. The polymer vesicles had a hydrophilic vesicular membrane which was favorable for the penetration of water-soluble substances and exhibited prominent glucose-responsiveness at physiological pH 7.4. FITC-insulin as a model protein was encapsulated in the polymer vesicles and the glucose-triggered insulin release was investigated. † These two authors contribute equally to this work.

Novel amphiphilic glucose-responsive modified starch micelles for insulin delivery

“…In addition, the gels are large in size, up to micron dimensions, and are easily removed by the permeability and retention effect (EPR), which is undesirable for long circulation. 10 Particularly, self-assembled glucose-responsive micelles 7,[11][12][13] and vesicles 8,14 with PBA-containing polymers have shown uncommon and notable properties.…”

Polypeptide-participating complex nanoparticles with improved salt-tolerance as excellent candidates for intelligent insulin delivery

“…51 Lately, Shi and his coworkers further studied the glucose-sensitivity of nanoparticles formed from poly(N-isopropylacrylamide)-block-poly(aspartic acid-co-aspart amido phenylboronic acid)/poly(aspartic acid-co-aspartamido glucose)-block-poly(ethylene glycol). 52 However, in those cases, it is mainly focused on the impact of the modiable carboxyl side group of the synthetic polypeptides on the glucose-responsiveness and biocompatibility of the overall materials.…”

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

“…Among these nano-carriers, the temperature response nano-carriers with special structure by using the temperature sensitivity of poly(N-isopropylacrylamide) (PNIPAM) can control the release of insulin by selfadjusting 'on/off ' mode and protect drugs from the degradation of enzymes, which have great potential application value in the treatment of diabetes [14][15][16][17][18]. Shi and co-workers prepared complex polymeric micelle (CPM) through the self-assembly of two types of diblock copolymers, poly(ethylene glycol)-b-poly(aspartic acidco-aspartamidophenylboronic acid) (PEG-b-P(Asp-co-AspPBA)) and poly(N-isopropylacrylamide)-b-poly (aspartic acid-co-aspartamidophenylboronic acid) (PNIPAM-b-P(Asp-co-AspPBA)) [15].…”

“…The cross-linking between PBA-and GA-containing blocks can enhance the stability of the shell. Therefore, the addition of a GA-containing block copolymer PEG-b-P (Asp-co-AspGA) resulted in the formation of core-shell-corona (CSC) complex micelles had a hydrophilic vesicular membrane which was favorable for the penetration of water-soluble substances and exhibited prominent glucose-responsiveness at physiological pH 7.4 [17,18]. With the development of nanotechnology, nanoscale drug carriers are attracting more and more attention [19,20].…”