Temperature-Responsive Poly(N-Isopropylacrylamide) Nanogels: The Role of Hollow Cavities and Different Shell Cross-Linking Densities on Doxorubicin Loading and Release

Abstract

Smart polymers with extraordinary characteristics are studied in drug-delivery applications. In the current study, temperature-responsive hybrid core−shell nanoparticles were synthesized by precipitation polymerization of N-isopropylacrylamide and vinyl-modified silica nanoparticles. These temperature-responsive hybrid core−shells were prepared with different cross-linking densities by using 2, 4, and 8 mol % of N,N-methylene bisacrylamide (MBA). Hydrolysis of the silica cores of the hybrid core−shells resulted in hollow poly(Nisopropylacrylamide) (PNIPAM) nanogels. Functionalization of silica nanoparticles with vinylcontaining silane modifier of 3-(trimethoxysilyl) propyl methacrylate (MPS) in two different contents was proven by Fourier transform infrared spectroscopy. Preparation of the hybrid PNIPAM nanogels and etching of the silica cores were studied using thermogravimetric analysis and also electron microscopy imaging. Sensitivity of the PNIPAM nanogel samples to temperature was studied using ultraviolet−visible (UV−vis) spectroscopy. In addition, dynamic light scattering was used for investigation of the squeezing and expansion of the hybrid and hollow samples against variation of temperature. The UV−vis spectroscopy results display higher absorption intensities in higher contents of MPS modifier and MBA cross-linker. The swelling content of the nanogels with hollow cavities was higher than that of the hybrid samples. The hybrid nanogels with 2 and 8 wt % silica content and different cross-linking densities and also their hollow nanoparticles were used for loading and release of doxorubicin (DOX). The release characteristics of the DOX-loaded nanogels were studied at different temperatures using UV−vis spectroscopy. The DOX release was higher at temperatures lower than the gel collapse temperature of the PNIPAM network. Although the nanogels with hollow cavities displayed higher loading capacities, the release percentage was higher for the hybrid PNIPAM nanogels, which was confirmed by the experimental release profiles and mathematical models. The most appropriate fitting of the DOX release data from the PNIPAM nanogel samples was observed for the Korsmeyer−Peppas model. Cytotoxicity studies on HeLa cell line showed that drug-loaded hollow samples showed higher toxicity due to loading of a higher amount of DOX.

Design and Applications of Tumor Microenvironment-Responsive Nanogels as Drug Carriers

“…For example, Luckanagul reported the synthesis of chitosan-based nanogels with modification by thermo-sensitive PNIPAM and CUR was successfully loaded through a simple sonication method in aqueous media, showing temperature-responsive drug release behaviors (Luckanagul et al, 2018b). In order to study the influence of the degree of crosslinking and the existence of holes in the nanogels on the drug loading and release characteristics, Hajebi synthesized temperature-responsive hybrid core-shell nanogels using NIPAM and vinyl-modified silica nanoparticles via precipitation polymerization, and hollow PNIPAM nanogels were obtained by hydrolysis of silicic acid (Hajebi et al, 2020). All results demonstrated that the hollow nanogels had higher DOX loading content and higher toxicity, whereas hybrid nanogels showed faster drug release.…”

Temperature Controlled Loading and Release of the Anti-Inflammatory Drug Cannabidiol by Smart Microgels

“…Regarding the use of microgels as drug-delivery vehicles, many different studies have been performed with varying drugs, ranging from lysozyme [ 24 ] over the more hydrophilic drugs dopamine, naproxen, desipramine, dibucaine, acetaminophen [ 25 ], and -aescin [ 26 ] to the hydrophobic doxorubicin (DOX) [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Just from these representative examples, it can be stated that the structure of microgels, which often exhibit a rather hydrophobic, cross-linker rich core region and a rather hydrophilic corona [ 34 ], enables these particles to act as carriers for a variety of hydrophilic and hydrophobic drugs.…”

A bio‐inspired gelatin‐based pH‐ and thermal‐sensitive magnetic hydrogel for in vitro chemo/hyperthermia treatment of breast cancer cells

“…Amongst, "smart" chemotherapy using stimuli-responsive hydrogels based on natural polymers have received more interest owing to intrinsic physicochemical and biological properties of these drug delivery systems (DDSs). [5][6][7][8][9] Amongst the variety of natural polymers, gelatin (Gel) as a thermo-sensitive natural polypeptide is widely used for the fabrication of de novo DDSs. It isolated from animal collagen through partial acidic (type A), alkaline (type B), or enzymatic hydrolysis that can be utilize in pharmaceutical technology as hard or soft capsules.…”

“…Despite the specific advantages of above‐mentioned approaches, off‐targeting of their have been challenged in most cases. Amongst, “smart” chemotherapy using stimuli‐responsive hydrogels based on natural polymers have received more interest owing to intrinsic physicochemical and biological properties of these drug delivery systems (DDSs) 5–9 …”