Enhanced Tumor Treatment Outcomes of PEGylated Liposomal Gefitinib in Non-Small Cell Lung Cancer: A Comprehensive Preclinical Evaluation with Superior Therapeutic Efficacy

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2025-10-08 DOI:10.1208/s12249-025-03235-z

Rajeshkumar S. Palva, Jolly R. Parikh, Rajnikant M. Suthar, Musaratafrin Saiyed, Mitali Patel, Prajesh Prajapati, Umang H. Shah

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Abstract

This study developed PEGylated liposomal gefitinib (GTL) to overcome clinical limitations of gefitinib therapy in NSCLC, including poor tumor targeting and suboptimal therapeutic outcomes. GTL was formulated using DPPC:cholesterol:mPEG-2000-DSPE (8:7:1) and comprehensively evaluated for tumor treatment efficacy. GTL achieved optimal physicochemical properties (87.7 ± 4.81 nm, EE 60.15%) with polymer relaxation-controlled release kinetics (Super Case II transport, n = 1.0789) providing sustained therapeutic exposure. The GTL demonstrated superior tumor treatment outcomes with threefold enhanced cytotoxicity (IC₅₀: 4.93 vs 15.03 μg/mL) and remarkable in vivo efficacy including 57% tumor volume reduction versus control and 32% superiority over free gefitinib. Comprehensive tumor treatment evaluation revealed enhanced apoptotic activity (68.35% caspase 3/7 activation), near-complete restoration of normal lung architecture, and significant tumor clearance confirmed by histopathological analysis. The controlled release mechanism enabled sustained therapeutic levels while minimizing systemic toxicity. GTL maintained stability for 12 months under ICH conditions, supporting clinical development. This work represents the comprehensive tumor treatment evaluation of gefitinib nanoformulation, demonstrating clinically relevant therapeutic superiority for improved NSCLC patient outcomes.

Graphical Abstract

Abstract Image

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聚乙二醇化吉非替尼脂质体治疗非小细胞肺癌的疗效：具有优越疗效的综合临床前评价

本研究开发了聚乙二醇化吉非替尼脂质体（GTL），以克服吉非替尼治疗非小细胞肺癌的临床局限性，包括肿瘤靶向性差和治疗效果欠佳。采用DPPC：胆固醇：mPEG-2000-DSPE（8:7:1）配制GTL，综合评价肿瘤治疗效果。GTL获得了最佳的物理化学性质（87.7±4.81 nm, EE 60.15%），聚合物弛缓控制释放动力学（超级案例II运输，n = 1.0789）提供了持续的治疗暴露。GTL表现出优异的肿瘤治疗效果，细胞毒性增强三倍（IC₅₀：4.93 vs 15.03 μg/mL），体内疗效显著，与对照组相比，肿瘤体积缩小57%，比游离吉非替尼优势32%。综合肿瘤治疗评估显示，凋亡活性增强（68.35%的caspase 3/7激活），肺结构几乎完全恢复正常，组织病理学分析证实肿瘤清除明显。控制释放机制使持续的治疗水平，同时尽量减少全身毒性。在ICH条件下，GTL保持稳定12个月，支持临床发展。这项工作代表了吉非替尼纳米制剂的综合肿瘤治疗评价，证明了改善非小细胞肺癌患者预后的临床相关治疗优势。

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.