Dual pH- and Thermo-Sensitive Poly(N-isopropylacrylamide-co-allylamine) Nanogels for Curcumin Delivery: Swelling–Deswelling Behavior and Phase Transition Mechanism

Abstract

Curcumin (Cur) is a beneficial ingredient with numerous bioactivities. However, due to its low solubility and poor bioavailability, its therapeutic application is limited. In this work, we prepared poly-N-isopropylacrylamide p(NIPAm) and polyallylamine p(Am)-based nanogel (p(NIPAm-co-Am)) NG for a dual pH- and temperature-sensitive copolymer system for drug delivery application. In this copolymer system, the p(NIPAm) segment was incorporated to introduce thermoresponsive behavior and the p(Am) segment was incorporated to introduce drug binding sites (amine groups) in the resulting (p(NIPAm-co-Am)) NG system. Various instrumental characterizations including 1H nuclear magnetic resonance (1H NMR) spectroscopy, Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM), zeta potential, and particle size analysis were performed to confirm the copolymer synthesis. Curcumin (Cur), an anticancer bioactive substance, was employed to assess the in vitro drug loading and release performance of the resulting copolymer nanogels system at varied pH levels (pH 7.2, 6.5, and 4.0) and temperatures (25 °C, 37 °C, and 42 °C). The cytocompatibility of the p(NIPAm-co-Am) NG sample was also tested on MDA-MB-231 cells at various sample concentrations. All the study results indicate that the p(NIPAm-co-Am) NG produced might be effective for drug loading and release under pH and temperature dual-stimuli conditions. As a result, the p(NIPAm-co-Am) NG system has the potential to be beneficial in the use of drug delivery applications in cancer therapy.

Biocompatible Anisole-Nonlinear PEG Core–Shell Nanogels for High Loading Capacity, Excellent Stability, and Controlled Release of Curcumin

“…The curcumin loading efficiency was 44.9%, 71.2%, 77.5%, 86.2%, and 92.3% for the PVAS core, VEM1, VEM2, VEM3, and VEM4 nanogels, respectively. The curcumin loading efficiencies of our nanogels are comparable to those of other nanogel-based curcumin carriers [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. However, the loading capacity of our core–shell nanogels are much higher than most other nanogel curcumin carriers [ 44 , 45 , 46 , 47 , 50 , 51 ], except a lignin-g-P(NIPAM-co-DMAEMA) nanogel with a hydrophobic lignin core [ 49 ].…”

“…The curcumin loading efficiencies of our nanogels are comparable to those of other nanogel-based curcumin carriers [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. However, the loading capacity of our core–shell nanogels are much higher than most other nanogel curcumin carriers [ 44 , 45 , 46 , 47 , 50 , 51 ], except a lignin-g-P(NIPAM-co-DMAEMA) nanogel with a hydrophobic lignin core [ 49 ]. Clearly, the addition of the hydrophilic nonlinear PEG gel shell onto the PVAS core can significantly enhance the curcumin loading capacity of the PVAS@PEG nanogels.…”

“…In another trial, 50 patients received a single intravenous dose of liposomal curcumin in the range of 10–400 mg/m 2 over 2 h. While the dosages ≥120 mg/m 2 already changed the red blood cell morphology, the curcumin and its metabolites in plasma became undetectable within 6–60 min [ 19 ]. In order to improve the bioavailability of curcumin, a variety of nanocarriers for curcumin have been developed [ 20 , 21 , 22 ], including polymer micelles [ 23 , 24 , 25 , 26 ], liposomes [ 27 , 28 , 29 , 30 ], inorganic nanoparticles [ 31 , 32 , 33 ], porous silica/metal–organic frames [ 34 , 35 , 36 ], biopolymer complexes/nanoparticles [ 37 , 38 , 39 , 40 , 41 ], and nanogels [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. However, most of these nanocarriers developed so far exhibit a low loading capacity, which still limits the bioavailability of curcumin for clinical use.…”

“…While curcumin loaded in this nanogel has a remarkably higher systemic bioavailability than free curcumin in an animal model, the therapeutic efficacy is still very limited due to the very low curcumin loading capacity (only 1.0–1.5 wt%) because of the hydrophilic nature of the nanogel. To introduce a dual-responsive curcumin delivery property, a variety of copolymer nanogels based on the thermosensitive poly( N -isopropylacrylamide) (pNIPAM) incorporated with pH-sensitive chitosan, poly( N , N -dimethylaminoethylmethacrylate) (pDMAEMA), and poly(allylamine) have been developed [ 48 , 49 , 50 ]. The incorporation of Au nanoparticles (NPs) in the polymer nanogels can induce a photothermal responsive release of curcumin [ 51 , 55 ].…”

Biocompatible Anisole-Nonlinear PEG core-shell Nanogels for High Loading Capacity, Excellent Stability, and Controlled Release of Curcumin

“…In another trial, 50 patients received a single intravenous dose of liposomal curcumin in the range of 10-400 mg/m 2 over 2 h. While the dosages ≥120 mg/m 2 already changed the red blood cell morphology, the curcumin and its metabolites in plasma became undetectable within 6-60 min [19]. In order to improve the bioavailability of curcumin, a variety of nanocarriers for curcumin have been developed [20][21][22], including polymer Gels 2023, 9, 762 2 of 18 micelles [23][24][25][26], liposomes [27][28][29][30], inorganic nanoparticles [31][32][33], porous silica/metalorganic frames [34][35][36], biopolymer complexes/nanoparticles [37][38][39][40][41], and nanogels [42][43][44][45][46][47][48][49][50][51]. However, most of these nanocarriers developed so far exhibit a low loading capacity, which still limits the bioavailability of curcumin for clinical use.…”