Sustained and Step-Wise Drug Release by a Novel Double Responsive Dendrimer-<i>N</i>-Acetylcysteine Conjugate
BIOMACROMOLECULES, vol.26, no.7, pp.4274-4285, 2025 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 26 Issue: 7
- Publication Date: 2025
- Doi Number: 10.1021/acs.biomac.5c00283
- Journal Name: BIOMACROMOLECULES
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, MEDLINE
- Page Numbers: pp.4274-4285
- Acibadem Mehmet Ali Aydinlar University Affiliated: No
Abstract
Polyamidoamine (PAMAM) dendrimers have emerged as promising vehicles for targeting the brain due to their intrinsic ability to penetrate through the injured blood-brain barrier. Herein, we present a novel drug delivery system based on a fourth generation PAMAM dendrimer as a brain targeting nanomedicine for the delivery of an anti-inflammatory drug N-acetyl cysteine with a sustained drug release profile. This D"ester"(NAC"ss"NAC) design enables NACs conjugated to the periphery of PAMAM dendrimers in the dimer form with ester and disulfide bonds to be sequentially released in a stepwise manner, responding to environmental pH and redox potential. Moreover, in vitro studies were conducted with a fluorescently labeled conjugate to confirm its nontoxic behavior and time-dependent cellular uptake, together with improved anti-inflammatory and antioxidative effects over endotoxin-activated microglia. These findings demonstrate that the DNACNAC conjugate has a high potential to be utilized as a promising dendrimer-based nanomedicine platform for prolonged treatment of neuroinflammation-related CNS disorders.