Sivasankaran Lekshmi Geetha, Rahim Suriya, Sreenivasan Anirudhan Thayyath
Department of Chemistry, Research Centre, School of Physical and Mathematical Sciences, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, India.
Department of Chemistry, Research Centre, School of Physical and Mathematical Sciences, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, India.
Eur J Pharm Biopharm. 2025 Jun;211:114718. doi: 10.1016/j.ejpb.2025.114718. Epub 2025 Apr 9.
Curcumin (CUR) is a natural herb with known anticancer effects against many malignancies such as breast cancer. However, CUR is poorly water-soluble and suffers from low bioavailability, and its delivery to breast cancer through oral administration is interrupted by early release and degradation before reaching the target site. So, this study aimed to develop an oral breast cancer-targeted drug delivery system (DDS) using a combination of biopolymers like mucoadhesive carboxymethyl chitosan, oleic acid and gelatin to create biopolymer-mediated nanoparticles (NPs) for the delivery of hydrophobic CUR. Gelatin-Oleic acid-Carboxymethyl chitosan (GOC) readily self-assembles into nanoparticles (GOCNPs) using the desolvation process. Such self-assembled DDS based on biopolymers without any crosslinkers for the preparation present controlled drug release and enhanced anticancer efficacy compared to existing systems. The prepared GOCNPs were characterized by FTIR, HNMR, XRD, SEM, HRTEM, DLS, and Zeta analysis. The DDS's maximum drug loading efficiency (DLE) and encapsulation efficiency (EE) values at pH 4.0 were 78.0 ± 2.34 % and 94.0 ± 2.8 %, respectively. The CUR-loaded GOCNPs shows a 90.0 ± 2.6 % CUR release at pH 5.5, while the release percentage of CUR at pH 7.4 was only 37.0 ± 1.06 %. According to the MTT data, CUR-GOCNPs show significant cytotoxicity to MCF-7 cells, showed a cell viability of 20.16 % towards MCF-7 cancer cells and loading of CUR to the GOCNPs notably increased its anticancer activity as the IC50 of CUR-GOCNPs was significantly lowered (6.880 µg/mL against MCF-7 in 24 h analysis). Studies on drug release kinetics, cytotoxicity, apoptosis, hemocompatibility, swelling, and in vivo pharmacokinetics were carried out to prove the effectiveness of the biopolymer-based nanoparticles developed as an effective oral delivery system for CUR. The future holds enormous possibilities for the clinical translation of prepared drug delivery system, as advances in controlled drug delivery continue to prove the design and capabilities of GOCNPs.
姜黄素(CUR)是一种天然草药,对许多恶性肿瘤如乳腺癌具有已知的抗癌作用。然而,CUR水溶性差且生物利用度低,通过口服给药将其递送至乳腺癌时,在到达靶位点之前会因早期释放和降解而受到阻碍。因此,本研究旨在开发一种口服乳腺癌靶向药物递送系统(DDS),使用粘膜粘附性羧甲基壳聚糖、油酸和明胶等生物聚合物的组合来制备生物聚合物介导的纳米颗粒(NPs),用于递送疏水性CUR。明胶 - 油酸 - 羧甲基壳聚糖(GOC)使用去溶剂化过程很容易自组装成纳米颗粒(GOCNPs)。与现有系统相比,这种基于生物聚合物且无需任何交联剂制备的自组装DDS呈现出可控的药物释放和增强的抗癌功效。通过傅里叶变换红外光谱(FTIR)、核磁共振氢谱(HNMR)、X射线衍射(XRD)、扫描电子显微镜(SEM)、高分辨率透射电子显微镜(HRTEM)、动态光散射(DLS)和Zeta分析对制备的GOCNPs进行了表征。该DDS在pH 4.0时的最大药物负载效率(DLE)和包封效率(EE)值分别为78.0±2.34%和94.0±2.8%。负载CUR的GOCNPs在pH 5.5时显示90.0±2.6%的CUR释放,而在pH 7.4时CUR的释放百分比仅为37.0±1.06%。根据MTT数据,CUR - GOCNPs对MCF - 7细胞显示出显著的细胞毒性,对MCF - 7癌细胞的细胞活力为20.16%,并且将CUR负载到GOCNPs中显著提高了其抗癌活性,因为CUR - GOCNPs的半数抑制浓度(IC50)显著降低(在24小时分析中对MCF - 7为6.880μg/mL)。进行了药物释放动力学、细胞毒性、凋亡、血液相容性、溶胀和体内药代动力学研究,以证明所开发的基于生物聚合物的纳米颗粒作为CUR有效口服递送系统的有效性。随着药物控释技术的进步不断证明GOCNPs 的设计和性能,所制备的药物递送系统的临床转化前景广阔。