Giri Paras Mani, Ghosal Arpita, Kruse Travis, Layek Buddhadev
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, United States.
Department of Pharmacy Practice, North Dakota State University, Fargo, North Dakota, United States.
J Drug Deliv Sci Technol. 2025 Nov;113. doi: 10.1016/j.jddst.2025.107341. Epub 2025 Jul 30.
Panobinostat is a highly active and potent non-selective histone deacetylase inhibitor (HDACi) that demonstrates significant anticancer activity against various cancers, including pancreatic cancer. However, like other HDAC inhibitors, its anticancer efficacy is often limited due to factors such as hydrophobicity, non-specificity to tumor cells, and poor pharmacokinetics. To overcome these limitations, encapsulating panobinostat in nanocarriers can enhance controlled drug release and increase cellular uptake, thereby improving therapeutic efficacy. In this study, bovine serum albumin (BSA) was utilized as a nanomaterial due to its nontoxicity, biocompatibility, and biodegradability. Initially, various drug-to-polymer ratios were tested to determine the optimal ratio for efficient loading and encapsulation. The BSA nanocarriers were prepared through a self-assembly method, and a drug-to-polymer ratio of 1:2.5 resulted in the highest loading and encapsulation efficiencies of 19.9% and 47.7%, respectively. The hydrodynamic diameter and zeta potential of the optimized nanoparticles were measured at 224.9 ± 5.0 nm and -28.6 ± 0.8 mV, respectively. Results from various physicochemical tests, including FTIR, XRD, DSC, and CD, confirmed the stability of the panobinostat-loaded nanocarriers. In vitro cytotoxicity studies indicated that nanoencapsulation significantly enhanced the anticancer efficacy of panobinostat compared to its free form.
帕比司他是一种高效且强效的非选择性组蛋白去乙酰化酶抑制剂(HDACi),对包括胰腺癌在内的多种癌症均表现出显著的抗癌活性。然而,与其他HDAC抑制剂一样,由于疏水性、对肿瘤细胞的非特异性以及较差的药代动力学等因素,其抗癌疗效往往受到限制。为克服这些局限性,将帕比司他封装于纳米载体中可增强药物的控释并增加细胞摄取,从而提高治疗效果。在本研究中,牛血清白蛋白(BSA)因其无毒、生物相容性和可生物降解性而被用作纳米材料。最初,测试了各种药物与聚合物的比例,以确定有效负载和封装的最佳比例。通过自组装方法制备了BSA纳米载体,药物与聚合物比例为1:2.5时,负载效率和封装效率最高,分别为19.9%和47.7%。优化后的纳米颗粒的流体动力学直径和zeta电位分别测定为224.9±5.0 nm和-28.6±0.8 mV。包括FTIR、XRD、DSC和CD在内的各种物理化学测试结果证实了负载帕比司他的纳米载体的稳定性。体外细胞毒性研究表明,与游离形式相比,纳米封装显著增强了帕比司他的抗癌疗效。