Eluu Stanley C, Obayemi John D, Yiporo Danyuo, Salifu Ali A, Oko Augustine O, Onwudiwe Killian, Aina Toyin, Oparah Josephine C, Ezeala Chukwudi C, Etinosa Precious O, Osafo Sarah A, Ugwu Malachy C, Esimone Charles O, Soboyejo Winston O
Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Ifite Awka 420110, Nigeria.
Department of Biotechnology, Ebonyi State University, Abakaliki 480101, Nigeria.
J Funct Biomater. 2024 Jul 28;15(8):209. doi: 10.3390/jfb15080209.
This study presents LHRH conjugated drug delivery via a magnetite nanoparticle-modified microporous Poly-Di-Methyl-Siloxane (PDMS) system for the targeted suppression of triple-negative breast cancer cells. First, the MNP-modified PDMS devices are fabricated before loading with targeted and untargeted cancer drugs. The release kinetics from the devices are then studied before fitting the results to the Korsmeyer-Peppas model. Cell viability and cytotoxicity assessments are then presented using results from the Alamar blue assay. Apoptosis induction is then elucidated using flow cytometry. The in vitro drug release studies demonstrated a sustained and controlled release of unconjugated drugs (Prodigiosin and paclitaxel) and conjugated drugs [LHRH conjugated paclitaxel (PTX+LHRH) and LHRH-conjugated prodigiosin (PG+LHRH)] from the magnetite nanoparticle modified microporous PDMS devices for 30 days at 37 °C, 41 °C, and 44 °C. At 24, 48, 72, and 96 h, the groups loaded with conjugated drugs (PG+LHRH and PTX+LHRH) had a significantly higher ( < 0.05) percentage cell growth inhibition than the groups loaded with unconjugated drugs (PG and PTX). Additionally, throughout the study, the MNP+PDMS (without drug) group exhibited a steady rise in the percentage of cell growth inhibition. The flow cytometry results revealed a high incidence of early and late-stage apoptosis. The implications of the results are discussed for the development of biomedical devices for the localized and targeted release of cancer drugs that can prevent cancer recurrence following tumor resection.
本研究提出了一种通过磁铁矿纳米颗粒修饰的微孔聚二甲基硅氧烷(PDMS)系统进行促黄体激素释放激素(LHRH)偶联药物递送的方法,用于靶向抑制三阴性乳腺癌细胞。首先,制备MNP修饰的PDMS装置,然后加载靶向和非靶向抗癌药物。在将结果拟合到Korsmeyer-Peppas模型之前,先研究装置的释放动力学。然后使用阿拉玛蓝检测结果进行细胞活力和细胞毒性评估。接着通过流式细胞术阐明细胞凋亡诱导情况。体外药物释放研究表明,在37℃、41℃和44℃下,未偶联药物(灵菌红素和紫杉醇)以及偶联药物[LHRH偶联紫杉醇(PTX+LHRH)和LHRH偶联灵菌红素(PG+LHRH)]从磁铁矿纳米颗粒修饰的微孔PDMS装置中持续可控释放30天。在24、48、72和96小时时,加载偶联药物(PG+LHRH和PTX+LHRH)的组比加载未偶联药物(PG和PTX)的组具有显著更高(<0.05)的细胞生长抑制百分比。此外,在整个研究过程中,MNP+PDMS(无药物)组的细胞生长抑制百分比稳步上升。流式细胞术结果显示早期和晚期凋亡发生率较高。讨论了这些结果对于开发用于局部和靶向释放抗癌药物的生物医学装置的意义,这些装置可预防肿瘤切除后癌症复发。