TY - JOUR

T1 - Thermosensitive injectable fibrillar gels based on cellulose nanocrystals grafted with poly(N-isopropylacrylamide) as biocompatible brain implants

AU - Беляева, Анастасия

AU - Аверчук, Антон

AU - Розанова, Наталья

AU - Алексанрова, Ольга

AU - Соломаха, Ольга

AU - Нащекина, Юлия Александровна

AU - Коржиков-Влах, Виктор Александрович

AU - Юрченко , Станислав

AU - Салмина, Алла

AU - Коржикова-Влах, Евгения Георгиевна

AU - Морозова, Софья

PY - 2024/12/15

Y1 - 2024/12/15

N2 - Drug treatment of glioblastoma, the most aggressive and widespread form of brain cancer, is complicated due to the difficulty of penetration of chemotherapeutic drugs through the blood-brain barrier (BBB). Moreover, with surgical removal of tumors, in 90 % of cases they reappear near the original focus. To solve this problem, we propose to use hydrogel based on cellulose nanocrystals grafted with poly(N-isopropylacrylamide) (CNC-g-PNIPAM) as a promising material for filling postoperative cavities in the brain with the release of antitumor drugs. The CNC-g-PNIPAM is formed by “grafting to” method for precise control of molecular weight and grafting density. This colloidal system is liquid under injection conditions (at r. t.) and turns into a gel at human body temperature (when filling the postoperative area). It was shown for the first time that due to the rod-shaped of CNC, the gel has a fibrillar structure and, thus, mechanical properties similar to those of brain tissue, including nonlinear mechanics (strain-stiffening and compression softening). The biocompatibility of the hydrogel with primary brain cells is demonstrated. In addition, the release of the antitumor drug paclitaxel from the hydrogel and its antitumor activity is shown. The resulting nanocolloid system provides an innovative alternative approach to filling postoperative cavities and can be used for postoperative treatment due to the programmable release of drugs, as well as for in vitro modeling of tumor interaction with the BBB affecting drug transport in the brain.

AB - Drug treatment of glioblastoma, the most aggressive and widespread form of brain cancer, is complicated due to the difficulty of penetration of chemotherapeutic drugs through the blood-brain barrier (BBB). Moreover, with surgical removal of tumors, in 90 % of cases they reappear near the original focus. To solve this problem, we propose to use hydrogel based on cellulose nanocrystals grafted with poly(N-isopropylacrylamide) (CNC-g-PNIPAM) as a promising material for filling postoperative cavities in the brain with the release of antitumor drugs. The CNC-g-PNIPAM is formed by “grafting to” method for precise control of molecular weight and grafting density. This colloidal system is liquid under injection conditions (at r. t.) and turns into a gel at human body temperature (when filling the postoperative area). It was shown for the first time that due to the rod-shaped of CNC, the gel has a fibrillar structure and, thus, mechanical properties similar to those of brain tissue, including nonlinear mechanics (strain-stiffening and compression softening). The biocompatibility of the hydrogel with primary brain cells is demonstrated. In addition, the release of the antitumor drug paclitaxel from the hydrogel and its antitumor activity is shown. The resulting nanocolloid system provides an innovative alternative approach to filling postoperative cavities and can be used for postoperative treatment due to the programmable release of drugs, as well as for in vitro modeling of tumor interaction with the BBB affecting drug transport in the brain.

KW - фибриллярные гидрогели

KW - термочувствительное гелирование

KW - 3D печать

KW - нанокристаллы целлюлозы

KW - импланты в мозг

KW - 3D printing

KW - Brain implants

KW - Cellulose nanocrystals

KW - Fibrillar hydrogels

KW - Thermosensitive gelation

UR - https://www.mendeley.com/catalogue/6102816c-2471-38bc-9924-d8b289ce1c70/

U2 - 10.1016/j.carbpol.2024.122596

DO - 10.1016/j.carbpol.2024.122596

M3 - Article

VL - 346

JO - Carbohydrate Polymers

JF - Carbohydrate Polymers

SN - 0144-8617

M1 - 122596

ER -