Sardo Carla, Auriemma Giulia, Mazzacano Carmela, Conte Claudia, Piccolo Virgilio, Ciaglia Tania, Denel-Bobrowska Marta, Olejniczak Agnieszka B, Fiore Donatella, Proto Maria Chiara, Gazzerro Patrizia, Aquino Rita Patrizia
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy.
Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
Pharmaceutics. 2024 Jul 23;16(8):971. doi: 10.3390/pharmaceutics16080971.
In this study, the structural attributes of nanoparticles obtained by a renewable and non-immunogenic "inulinated" analog of the "pegylated" PLA (PEG-PLA) were examined, together with the potential of these novel nanocarriers in delivering poorly water-soluble drugs. Characterization of INU-PLA assemblies, encompassing critical aggregation concentration (CAC), NMR, DLS, LDE, and SEM analyses, was conducted to elucidate the core/shell architecture of the carriers and in vitro cyto- and hemo-compatibility were assayed. The entrapment and in vitro delivery of sorafenib tosylate () were also studied. INU-PLA copolymers exhibit distinctive features: (1) Crew-cut aggregates are formed with coronas of 2-4 nm; (2) a threshold surface density of 1 INU/nm triggers a configuration change; (3) INU surface density influences PLA core dynamics, with hydrophilic segment stretching affecting PLA distribution towards the interface. INU-PLA demonstrated an outstanding loading of and excellent biological profile, with effective internalization and delivery to HepG2 cells, yielding a comparable IC.
在本研究中,我们研究了通过可再生且无免疫原性的“聚乙二醇化”聚乳酸(PEG-PLA)的“菊粉化”类似物获得的纳米颗粒的结构属性,以及这些新型纳米载体在递送难溶性药物方面的潜力。对包含临界聚集浓度(CAC)、核磁共振(NMR)、动态光散射(DLS)、低温电子显微镜(LDE)和扫描电子显微镜(SEM)分析的菊粉-聚乳酸(INU-PLA)组装体进行了表征,以阐明载体的核/壳结构,并测定了体外细胞和血液相容性。还研究了甲苯磺酸索拉非尼()的包封和体外递送情况。INU-PLA共聚物具有独特的特征:(1)形成具有2-4纳米冠层的平头聚集体;(2)每纳米1个INU的阈值表面密度会引发构象变化;(3)INU表面密度影响PLA核动力学,亲水性链段的伸展影响PLA向界面的分布。INU-PLA表现出出色的包载量和优异的生物学特性,能有效地内化并将药物递送至HepG2细胞,产生相当的半数抑制浓度(IC)。