Donepezil nanocrystals-incorporated carboxymethyl cellulose nanopaste for high-payload transdermal delivery with improved skin compatibility.

Authors

In Gyu Yang, Jae Yoon Heo, Jin Hyuk Myung, Min Young Jeong, Jun Soo Park, Da Eun Kim, Su Yeon Noh, Min Gyeong Jeong, Min Ji Kim, Jun Yeop Kim, Dong-Wan Seo, Min-Koo Choi, Yong Seok Choi, Myung Joo Kang

Published in

International journal of biological macromolecules. Pages 153735. Jul 26, 2026. Epub Jul 26, 2026.

Abstract

Donepezil (DPZ), an acetylcholinesterase inhibitor for Alzheimer's disease, suffers from skin irritation during transdermal delivery. Herein, a drug high-payload nanopaste (NP) system was designed employing carboxymethyl cellulose (CMC) to enhance transdermal delivery of DPZ while mitigating cutaneous irritation. DPZ NPs (10, 20, and 27.5% w/v) were fabricated via wet bead-milling with low-molecular-weight CMC (90 K) to obtain submicron particles, followed by incorporation into high-molecular-weight CMC (700 K) matrix. The drug nanocrystals were uniformly distributed in the CMC matrix, preserving crystal size (505.6-563.8 nm), zeta potential (-48.93 to -51.95 mV), and crystallinity. Fourier-transform infrared analysis revealed the electrostatic interaction between the anionic polymers and drug nanocrystals. Pharmacokinetic evaluations in rats revealed that while the 10% NP achieved systemic absorption comparable to the commercial patch, the 20% NP provided a 2.1-fold higher transdermal absorption. Level A IVIVC analysis established a robust correlation (R² > 0.96) between in vitro dissolution profile and in vivo absorption. Crucially, the CMC-based NPs showed markedly improved dermal tolerability, showing minimal hyperplasia and inflammation compared to acrylic-based commercial patches. Additionally, NPs were chemically stable under accelerated conditions without antioxidants. These findings suggest that CMC-based NP system of DPZ represents a biocompatible transdermal platform for long-term Alzheimer's therapy.

PMID:
42503382
Bibliographic data and abstract were imported from PubMed on 27 Jul 2026.

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