Resveratrol encapsulation in high molecular weight chitosan-based nanogels for applications in ocular treatments: Impact on human ARPE-19 culture cells

• Published in: International journal of biological macromolecules 2020-12, Vol.165 (Pt A), p.804-821
• Main Authors: Buosi, Florencia Solana, Alaimo, Agustina, Di Santo, Mariana Carolina, Elías, Fernanda, García Liñares, Guadalupe, Acebedo, Sofía Lorena, Castañeda Cataña, Mayra Alejandra, Spagnuolo, Carla Cecilia, Lizarraga, Leonardo, Martínez, Karina Dafne, Pérez, Oscar Edgardo
• Format: Article
• Language: English
• Subjects: Antioxidants - chemistry; Antioxidants - pharmacokinetics; Antioxidants - pharmacology; Cell Line; Cellular uptake; Chitosan - chemistry; Chitosan - pharmacokinetics; Chitosan - pharmacology; High molecular weight chitosan; Humans; Nanocapsules - chemistry; Nanocapsules - therapeutic use; Nanogels; Nanogels - chemistry; Nanogels - therapeutic use; Ocular diseases; Resveratrol; Resveratrol - chemistry; Resveratrol - pharmacokinetics; Resveratrol - pharmacology; Retinal pigment epithelium; Retinal Pigment Epithelium - metabolism
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.09.234

Oxidative stress and inflammation play a pivotal role in ocular diseases. Resveratrol (RSV) is a natural bioactive that has recently attracted attention due to it potent antioxidant and anti-inflammatory properties. However, RSV presents poor aqueous solubility and chemical instability. Besides, effective drug delivery to the posterior segment of the eye is challenge. Nanotechnology emerges as a possible solution to improve both limitations. Here, we developed and characterized nanogels (NG) based on high molecular weight chitosan (HCS) crosslinked with sodium tripolyphosphate. The distribution size of NG presented a major population around 140 nm with a ζ-potential value of 32 ± 2 mV. TEM and AFM images showed that NG exhibited a rounded morphology. RSV encapsulation efficiency was 59 ± 1%. Photodegradation experiments showed that HCS by its own protects RSV from UV light-induced degradation. Biocompatibility assays revealed that NG were not cytotoxic neither inflammatory in human retinal pigment epithelial cells (ARPE-19), which constitutes the outer blood-retinal barrier. After cellular internalization, we report an endo-lysosomal escape of NG, which is crucial for efficient nanocarriers delivery systems. In conclusion, we envision that HCS based NG could constitute novel carriers for RSV, opening the possibility of its application in ocular diseases. [Display omitted] •High molecular weight chitosan (HCS) and TPP formed stable nanogels (NG).•Particles size agreed with ocular delivery queries.•Single HCS and NG were biocompatible with human ARPE-19 cells.•Single HCS and NG were rapidly internalized into ARPE-19 cells.•NG escaped from the endo/lysosomal acidic compartments.