Jafari-Najaf-Abadi Azam, Pazoki-Toroudi Hamidreza, Hadjianfar Mehdi, Mirjafary Zohreh, Faridi-Majidi Reza, Akbarzadeh Abolfazl
Department of Chemistry, SR.C., Islamic Azad University, Tehran, Iran.
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Sci Rep. 2025 Aug 4;15(1):28401. doi: 10.1038/s41598-025-14483-1.
Melanoma is the most aggressive type of skin cancer and has very high rates of mortality. The primary objective of this study was to fabricate core-shell nanofibers as a drug delivery system using the coaxial electrospinning technique, which provides some distinct features. Polycaprolactone (PCL)-chitosan (CS)/polyvinyl alcohol (PVA) core-shell nanofibers embedded with Pioglitazone hydrochloride-loaded Nanoemulsions (PIO NEs), a general anti-diabetic drug, and Gemcitabine hydrochloride (GEM), a chemotherapeutic agent, were prepared to investigate the effects of combination of GEM and PIO against A375 melanoma skin cancer cells in vitro. The prepared PCL-CS/PVA-PIO NEs-GEM core-shell nanofibers exhibited sustained and controlled release profiles of GEM and PIO NEs over 14 days, which was fitted into various kinetic models. The data demonstrated the efficacy of nanoemulsions in improving the solubility and release of the poorly aqueous soluble drug PIO. The maximum amount released from the core-shell nanofibers reached 76.99 ± 1.5% of the GEM and 80.47 ± 2.01% of the PIO in a medium of pH 7.4. The nanofibers' morphology, chemical composition, weight loss, and swelling behavior were evaluated. MTT and flow cytometry analyses demonstrated that the combination of PIO and GEM effectively inhibited the growth of melanoma cancer cell lines by inhibiting proliferation with cell viability of 47.07 ± 2.5%, 45.36 ± 2.8%, and 39.79 ± 1.8% after 24, 48 and 72 h, inducing G /G phase arrest and apoptosis, and exhibited an enhanced combinatorial effect in A375 cells in vitro. Additionally, real-time PCR analysis confirmed the induction of apoptosis by measuring gene expression levels, suggesting that the mechanism is associated with the P53 and PPARγ pathways. The generated core-shell nanofibers exhibit properties that suggest their potential as an innovative local drug delivery system, suitable for direct implantation at the tumor site for melanoma treatment through a unique combination therapy of PIO and GEM.
黑色素瘤是最具侵袭性的皮肤癌类型，死亡率很高。本研究的主要目的是使用同轴电纺技术制备核壳纳米纤维作为药物递送系统，该技术具有一些独特的特性。制备了包埋有盐酸吡格列酮负载纳米乳剂（PIO NEs）（一种常用的抗糖尿病药物）和盐酸吉西他滨（GEM）（一种化疗药物）的聚己内酯（PCL）-壳聚糖（CS）/聚乙烯醇（PVA）核壳纳米纤维，以研究GEM和PIO联合使用对A375黑色素瘤皮肤癌细胞的体外作用。制备的PCL-CS/PVA-PIO NEs-GEM核壳纳米纤维在14天内呈现出GEM和PIO NEs的持续和可控释放曲线，符合各种动力学模型。数据表明纳米乳剂在改善难溶性药物PIO的溶解度和释放方面的功效。在pH 7.4的介质中，从核壳纳米纤维释放的最大量达到GEM的76.99±1.5%和PIO的80.47±2.01%。对纳米纤维的形态、化学成分、失重和溶胀行为进行了评估。MTT和流式细胞术分析表明，PIO和GEM的联合使用通过抑制增殖有效抑制了黑色素瘤癌细胞系的生长，在24、48和72小时后细胞活力分别为47.07±2.5%、45.36±2.8%和39.79±1.8%，诱导G /G期阻滞和凋亡，并在体外对A375细胞表现出增强的联合作用。此外，实时PCR分析通过测量基因表达水平证实了凋亡的诱导，表明其机制与P53和PPARγ途径有关。所制备的核壳纳米纤维表现出的特性表明它们有潜力作为一种创新的局部药物递送系统，适用于通过PIO和GEM的独特联合疗法直接植入肿瘤部位治疗黑色素瘤。
