Central Composite Design Based Optimization of Carbohydrate Coated Albumin Nanoparticles for HCC: Synthesis, Extensive Characterization and In Vivo Pharmacokinetic Evaluation

IF 3.2 4区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biopolymers Pub Date : 2025-05-29 DOI:10.1002/bip.70028
Sanya Batheja, Rakesh K. Sahoo, Sarita Rani, Shruti Gupta, Kiran K. Tejavath, Sonal Sinha,  Ajazuddin, Awesh K. Yadav, Amit Kumar Goyal, Umesh Gupta
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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) is one serious cause of cancer-associated deaths worldwide. Poor bioavailability and non-specific targeting of drugs is a challenge. Gemcitabine (GEM) is broad-spectrum anticancer drug for liver and other cancers. In this study, an attempt to formulate drug-loaded galactosylated albumin-based nanoparticles (GEM-LA-BSA NPs) was made to increase the bioavailability and targetability of hydrophilic drugs. The formulation was optimized using central composite design for further evaluation and developed a pilot-scale approach for commercialization. LA-BSA conjugate was synthesized, characterized, and formulated into a nanoformulation. The particle size of the optimal formulation was 40.19 ± 7.98 nm with reduced drug release (57.78% ± 4.10%) in 48 h and aggregates-like structure by HR-TEM. In vitro studies in HepG2 cells indicated better cytotoxicity of GEM-LA-BSA NPs than GEM (IC50 values 226.42 ± 11.32 and 366.03 ± 11.93 μg/mL, respectively), while in vivo studies in SD rats exhibited almost two-fold bioavailability, better pharmacokinetics, and reduced IC50 portraying immense potential as an effective drug delivery system.

肝细胞癌碳水化合物包被白蛋白纳米颗粒的中心复合设计优化:合成、广泛表征和体内药代动力学评价
肝细胞癌(HCC)是世界范围内癌症相关死亡的一个严重原因。生物利用度差和药物的非特异性靶向是一个挑战。吉西他滨(GEM)是一种广谱抗肝癌药物。本研究试图制备载药半乳糖化白蛋白纳米颗粒(GEM-LA-BSA NPs),以提高亲水药物的生物利用度和靶向性。采用中心复合设计对配方进行了优化,以便进一步评估,并开发了商业化的中试方法。合成了LA-BSA缀合物,对其进行了表征,并配制成纳米制剂。最佳配方的粒径为40.19±7.98 nm, 48 h释药率降低57.78%±4.10%,经HR-TEM观察为聚集体状。体外HepG2细胞实验表明,GEM- la - bsa NPs的细胞毒性优于GEM (IC50值分别为226.42±11.32和366.03±11.93 μg/mL),而SD大鼠体内实验显示,GEM- la - bsa NPs具有近两倍的生物利用度、更好的药代动力学和更低的IC50,显示出作为一种有效的给药系统的巨大潜力。
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来源期刊
Biopolymers
Biopolymers 生物-生化与分子生物学
CiteScore
5.30
自引率
0.00%
发文量
48
审稿时长
3 months
期刊介绍: Founded in 1963, Biopolymers publishes strictly peer-reviewed papers examining naturally occurring and synthetic biological macromolecules. By including experimental and theoretical studies on the fundamental behaviour as well as applications of biopolymers, the journal serves the interdisciplinary biochemical, biophysical, biomaterials and biomedical research communities.
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