Smart Nanoformulation Based on Stimuli-Responsive Nanogels and Curcumin: Promising Therapy against Colon Cancer

Abstract

Curcumin (CUR) has gained much attention for its widely reported anticancer effect; however, its clinical use is restricted due to its low water solubility and, consequently, its poor bioavailability. Here, we report on the use of a nanoformulation of CUR with cationic nanogels for colon cancer therapy. Cationic stimuli-sensitive nanogels were prepared using a scale-up polymerization methodology based on surfactant-free emulsion polymerization of N,N′-diethylaminoethyl methacrylate (DEAEM) and poly­(ethyleneglycol) methacrylate (PEGMA). The obtained nanogels showed a homogeneous size distribution (from 51 to 162 nm, polydispersity index (PDI) < 0.138) and exhibited a spherical form and core–shell morphology as confirmed by dynamic light scattering and electron microscopy, respectively. Nanogels were responsive to and degradable by variations of pH, temperature, or the redox environment, depending on the cross-linker used in the synthesis. Nanogels cross-linked with bis­(acryloyl)­cystamine incubated in a buffer (pH 7.4) containing 3 mM glutathione degraded in 60 min, while nanogels cross-linked with a divinylacetal cross-linker degraded in 10 min (pH ≤ 6). Nanoformulations of nanogels with CUR were stable as tested up to 30 days at physiological conditions. In vitro studies of the human colon cancer cell line (HCT-116) showed a synergistic effect of CUR and the degradable nanogels. Further, in vivo acute cytotoxicity tests of empty nanogels in mice demonstrate their potential as CUR nanocarriers for colon-anticancer therapies.

Meta-analysis of In Vitro Drug-Release Parameters Reveals Predictable and Robust Kinetics for Redox-Responsive Drug-Conjugated Therapeutic Nanogels

“…Hence, for a redox-responsive nanogel, k would reflect how much of the drug loaded will be released shortly upon exposure to the stimulus. Here, k was defined as a fraction of the loaded drug released in the first hour, given the variability of the time frames used to measure in vitro drug release ranging from a minimum of 1.8 h to a maximum of 215 h (Supporting Information E1).…”

Nanogels as target drug delivery systems in cancer therapy: A review of the last decade

“…In addition, targeted drug delivery reduces adverse drug reactions which may lead to poor adherence to medications. Manzanares-Guevara et al (2020) developed nanogels using for targeted delivery of curcumin in colon cancer. They combined different materials using several methods to achieve targeted drug delivery with promising future applications.…”

Release kinetics and binding interactions of curcumin‐encapsulated nanoparticles released from chitosan‐graft‐(methoxy poly(ethylene glycol)‐block‐polycaprolactone) injectable hydrogels

“…Curcumin is a natural polyphenolic compound that has frequently been used as a model drug as an anticancer agent against various cancer cells and also possesses a wide range of biological activities such as antidiabetic, antimalarial, antimicrobial 13 . However, the poor solubility of curcumin in aqueous solution consequently leads to poor absorption and affects oral administration and hence bioavailability 14,15 . To improve the feasibility of curcumin in biomedical applications, such hydrophobic drugs are frequently encapsulated in delivery vehicles such as dendrimers, micelles, nanoemulsions, polymeric nanoparticles and solid lipid nanoparticles that can efficiently transport the encapsulated agent to the pathological site 9,16 .…”

“…13 However, the poor solubility of curcumin in aqueous solution consequently leads to poor absorption and affects oral administration and hence bioavailability. 14,15 To improve the feasibility of curcumin in biomedical applications, such hydrophobic drugs are frequently encapsulated in delivery vehicles such as dendrimers, micelles, nanoemulsions, polymeric nanoparticles and solid lipid nanoparticles that can efficiently transport the encapsulated agent to the pathological site. 9,16 Generally, preparation of drugencapsulated polymeric nanoparticles, including curcumin, can be achieved in two ways.…”