pH and reduction-activated polymeric prodrug nanoparticles based on a 6-thioguanine-dialdehyde sodium alginate conjugate for enhanced intracellular drug release in leukemia

Abstract

Synthesis schematics of DSA and 6-TG-DSA as well as processes of PPN self-assembly and its pH/GSH dual stimuli-response release of the conjugated 6-TG.

Advances in Thiopurine Drug Delivery: The Current State-of-the-Art

“…These approaches include liposomal delivery, micelles, microspheres and metallic and polymeric based nanoparticles (see Fig. 2) [66][67][68][69][70][71][72][73][74][75][76][77].…”

“…Other conjugated polymeric approaches have been described. These include thioguanine-dialdehyde sodium alginate nanoparticles [71], thioguanine-poly-lactic-coglycolic acid (PLGA) nanoparticles [73], azathioprinegelatin nanoparticles [94] and glutathione-sensitive hyaluronic acid-mercaptopurine nanoparticles [69]. Govindappa et al [70] studied the toxicity of mercaptopurine-conjugated chitosan nanoparticles in an animal model.…”

“…Significant amount of cytotoxicity 48 h after nanoparticle exposure, probably caused by intracellular uptake of TG nanoparticles by pinocytosis Rajashekarajah [ 68 ] India Polymer-based drug delivery TG Chitosan In vitro (PA-1 cells) Drug release pH 4.8 > pH 7.4 of TG nanoparticles after 48 h (91.4% vs 74.0%). IC 50 values of 5.8, 12.9 and 3.9 µM for TG, curcumin and TG nanoparticles Govindappa [ 70 ] India Polymer-based drug delivery MP Chitosan In vivo (Wistar rats) This study investigated the in vivo toxicity profile of MP-NPs and MP Ahmed [ 74 ] Egypt Polymer-based drug delivery MP Chitosan In vitro (MCF-7 cells) ↑ Cytotoxicity of MP NP compared to MP Decreased cell survival of 8% (3.1 µM) and 55% (6.2 µM) for MP and MP NP Wan [ 71 ] China Polymer-based drug delivery TG Dialdehyde sodium alginate In vitro (HL-60 cells) Drug release at pH 5.0 (98.6%), no drug release at pH 7.4 Qiu [ 69 ] China Polymer-based drug delivery MP Hyaluronic In vivo (nude mice) ↑ T 1/2 , ↑ reduction tumor volume for HA-MP compared to MP ( P < 0.01) Kumar [ 72 ] India Polymer-based drug delivery MP Chitosan In vivo (Wistar rats) ↑ C max , ↑ bioavailability, ↑ T 1/2 for MP-NP compared to MP. Cmax (ng/ml) of 25.3 (at 4 h) vs 13.5 (at 2 h) for MP-NP and MP.…”

pH-responsive polymeric nanoparticles with tunable sizes for targeted drug delivery

“…The hydrolysis of Schiff base linkages can only start from the NPs surface in weakly acid conditions and slowly penetrate the interior of the NPs, leading to the shrinkage of the core, while the shell becomes swollen and loose. [43][44][45][46] Among the three kinds of NPs in aqueous solutions at pH 4.0, the stability of the NPs changed in the following order: NPs-O 1:1 > NPs-H 1:1 > NPs-R 1:1 . Therefore, the larger the side chains are for the formation of NPs, the more difficult it is for H + to penetrate the interior of the NPs to disassemble hydrophobic cores.…”

Preparation of High-Performance Composite Hydrogel Reinforced by Hydrophilic Modified Waste Rubber Powder

“…As a high water-containing polymer with a three-dimensional cross-linked network structure, hydrogel is widely used in biomedicine [ 25 , 26 , 27 ], industry [ 28 , 29 ], agriculture, and in other fields [ 30 , 31 , 32 ] due to its unique properties. However, traditional synthetic hydrogels have the problems of the uneven distribution of the cross-linking points and the lack of energy dissipation mechanisms, resulting in poor mechanical properties, which greatly limit the application of hydrogels [ 33 ].…”