Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer

IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL Journal of Materials Science: Materials in Medicine Pub Date : 2023-08-02 DOI:10.1007/s10856-023-06738-y
Chukwudalu C. Nwazojie, John D. Obayemi, Ali A. Salifu, Sandra M. Borbor-Sawyer, Vanessa O. Uzonwanne, Chinyerem E. Onyekanne, Udom M. Akpan, Killian C. Onwudiwe, Josephine C. Oparah, Olushola S. Odusanya, Winston O. Soboyejo
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Abstract

The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer–Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection.

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靶向载药PLGA-PCL微球用于特异性和局部治疗三阴性乳腺癌
本文介绍了由聚乳酸-羟基乙酸-聚己内酯共混聚合物(PLGA-PCL)制备的靶向载药聚合物微球用于靶向和局部肿瘤药物递送的实验和分析研究结果。在三个月的时间里,研究了包封的靶向药物(Prodigiosin - epha2或paclitaxel- epha2)和对照药物(Prodigiosin (PGS)和paclitaxel (PTX))的体外缓释动力学。体外研究结果显示,在37°C(体温)、41°C和44°C(高温)的温度范围内,非菲氏Korsmeyer-Peppas动力学模型很好地表征了药物的持续和局部释放。体外alamar blue和流式细胞术检测显示,不同的载药聚合物配方会导致细胞死亡和细胞毒性,这一点通过三阴性乳腺癌(TNBC)细胞的细胞抑制和晚期凋亡得到了证明(MDA-MB 231)。对皮下TNBC诱导的4周龄胸腺裸小鼠进行的体内研究表明,局部手术切除后,epha2偶联药物的局部释放可以有效地完全消除残留肿瘤。最后,对安乐死小鼠进行的离体组织病理学分析显示,治疗12周后,没有细胞毒性,肝脏、肾脏和肺部没有乳腺癌转移。然后讨论了研究结果对开发epha2缀合的囊化药物制剂的意义,该制剂具有特异性靶向、局部和持续释放药物的功能,以消除手术切除后局部复发的TNBC肿瘤。图形抽象
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来源期刊
Journal of Materials Science: Materials in Medicine
Journal of Materials Science: Materials in Medicine 工程技术-材料科学:生物材料
CiteScore
8.00
自引率
0.00%
发文量
73
审稿时长
3.5 months
期刊介绍: The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.
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