Hy Dinh Nguyen (아주대학교)

한빛사논문

조회77

아주대학교

CV File 575 kb

Adv. Sci., Sep 03 2024, | https://doi.org/10.1002/advs.202405200 Novel pH-Responsive Structural Rearrangement of Myristic Acid-Conjugated Quetiapine Nanosuspension for Enhanced Long-Acting Delivery Performance

Hy Dinh Nguyen ¹, Hai Van Ngo ¹, Beom-Jin Lee^1,2

¹Department of Pharmacy, College of Pharmacy, Ajou University, Suwon, 16499, Republic of Korea.

²Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, 16499, Republic of Korea.

Corresponding Author: Beom-Jin Lee

Abstract

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35 mg kg^-1 QTP), QMN undergoes pH-responsive nanoaggregation to form the lipophilic prodrug, providing esterase-oriented sustained release for five weeks compared with the two-week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long-acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long-acting injectable to improve patient compliance and dosing frequency.

논문정보

형식Research article
게재일2024년 09월 (BRIC 등록일 2024-09-05)
연구진국내 연구진
분야 의약학 > 약학

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