Functional Nanogel from Natural Substances for Delivery of Doxorubicin

Abstract

Nanogels (NGs) have attracted great attention because of their outstanding biocompatibility, biodegradability, very low toxicity, flexibility, and softness. NGs are characterized with a low and nonspecific interaction with blood proteins, meaning that they do not induce any immunological responses in the body. Due to these properties, NGs are considered promising candidates for pharmaceutical and biomedical application. In this work, we introduce the development of novel functional nanogel obtained from two naturally based products—citric acid (CA) and pentane-1,2,5-triol (PT). The nanogel was synthesized by precipitation esterification reaction of CA and PT in tetrahydrofuran using N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide (EDC) and 4-(dimethylamino)pyridine (DMAP) catalyst system. Dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM) analyses revealed formation of spherical nanogel particles with a negative surface charge. Next, the nanogel was loaded with doxorubicin hydrochloride (DOX) by electrostatic interactions between carboxylic groups present in the nanogel and amino groups of DOX. The drug-loaded nanogel exhibited high encapsulation efficiency (EE~95%), and a bi-phasic release behavior. Embedding DOX into nanogel also stabilized the drug against photodegradation. The degradability of nanogel under acidic and neutral conditions with time was investigated as well.

Functional Hydrogels for Delivery of the Proteolytic Enzyme Serratiopeptidase

“…Figure 2 shows the FTIR spectra of PA, CA, PEG, and the formed polymer networks at different molar ratio of reagents. The FTIR spectra of PT and PEG-600 show identical characteristic peaks at 3500–3200 cm −1 , assigned to the stretching vibration of O–H bonds; 2970 and 2820 cm −1 , corresponding to the stretching of C-H bonds; and 1050–1000 cm −1 , attributed to the C–O stretching of the alcohol [ 32 , 34 ]. CA exhibited characteristic signals at 3500–3000 cm −1 , from stretching vibrations of O-H bonds and C–H bonds; 1750 and 1690 cm −1 , corresponding to C=O stretching of the carboxylic groups of aliphatic carboxylic acid; 1180–1100 cm −1 , correlated with the C–O bonds; and 780 cm −1 , ascribed to CH 2 rocking [ 35 ].…”

“…CA exhibited characteristic signals at 3500–3000 cm −1 , from stretching vibrations of O-H bonds and C–H bonds; 1750 and 1690 cm −1 , corresponding to C=O stretching of the carboxylic groups of aliphatic carboxylic acid; 1180–1100 cm −1 , correlated with the C–O bonds; and 780 cm −1 , ascribed to CH 2 rocking [ 35 ]. The FTIR spectra of hydrogels have two new intensive bands which are typical for polyesters [ 32 , 36 ]. The appearance of stretching vibrations of C=O groups at 1726 cm −1 ( Figure 2 c) and twisting vibrations of CH 2 groups at 1192 cm −1 indicates the successful formation of ester bonds between –OH groups of PT and PEG and –COOH groups of CA [ 22 , 32 ].…”

“…PT is a renewable polyfunctional compound obtained from the furfural processing [ 31 ]. Recently, our research group has fabricated biocompatible and biodegradable nanogels for drug delivery, based on PT and CA, via precipitation polymerization through a Steglich esterification reaction with N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide (EDC) and a 4-dimethyl aminopyridine (DMAP) catalyst system in an organic solvent [ 32 ]. In the present work, the crosslinking of PT and PEG with CA was achieved by a facile, environment friendly process at an elevated temperature in the absence of any solvent.…”

Nano-Gels: Recent Advancement in Fabrication Methods for Mitigation of Skin Cancer

“…Drug loading in nano-gels can potentially be negatively impacted by cross-linking agents, which have been linked to severe side effects. In addition, by altering the physical conditions during formation, nano-gels can be made in any size for effective drug administration [ 10 , 56 ]. Kamenova et al (2022) synthesized photo-chemically stable citric acid and pentane-1,2,5-triol loaded spherical and negatively (surface) charged nano-gel in tetrahydrofuran by precipitation esterification process in the presence of two catalysts (N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide and 4 (dimethyl amino) pyridine).…”

“…Kamenova et al (2022) synthesized photo-chemically stable citric acid and pentane-1,2,5-triol loaded spherical and negatively (surface) charged nano-gel in tetrahydrofuran by precipitation esterification process in the presence of two catalysts (N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide and 4 (dimethyl amino) pyridine). Later, doxorubicin hydrochloride was introduced into the physically cross-linked nano-gel because of electrostatic interaction between carboxylic groups in the nano-gel and amino groups of the anticancer drug exhibiting almost 95% entrapment efficiency with bi-phasic release kinetics [ 56 ]. Polymers created through covalent chemical interactions make up chemically cross-linked nano-gels.…”