Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer
Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer
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DOI：
10.1016/j.ijbiomac.2020.02.275
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发表时间：
2020-06-01
影响因子：
8.2
通讯作者：
Shahnaz, Gul
中科院分区：
文献类型：
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作者：
Batool, Ayesha;Arshad, Rabia;Shahnaz, Gul
本研究旨在开发一种木瓜蛋白酶接枝S保护的透明质酸-胆酸共嵌段聚合物赋形剂(PAP-HA-ss-LCA)作为两亲性粘液渗透稳定剂，用于靶向CD44R高表达的乳腺癌上皮细胞。通过制备他莫昔芬(TMX)自纳米乳化给药系统(SNEDDS)，考察了PAP-HA-ss-LCA聚合物辅料的粘液渗透、稳定和靶向性能。对TMX-PAP-HA-ss-LCA复合SNEDDS(TMX-PAP-HA-ss-LCA SNEDDS)进行了表面化学、药物释放、促透作用、生物相容性和抗肿瘤活性的表征。红外光谱分析表明成功合成了PAP-HA-ss-LCA聚合物。X-射线衍射仪(XRD)显示SNEDDS中的TMX为无定形。观察到TMX-PAP-HA-ss-LCA SNEDDS的流体力学直径为367.5 nm。此外，TMX基于透明质酸的粘附性自纳米乳化给药系统(SNEDDS)在合成过程中表现出均一性，由于PAP-HA-ss-LCA聚合物的稳定，其多分散性低，且Zeta电位为负。通过透射电子显微镜观察，纳米液滴呈明显的球形。体外释放动力学研究表明，在下沉条件下，药物在48小时内释放约80%。体外透皮实验表明，TMX-PAP-HA-ss-LCA对TMX的渗透率是纯TMX的7.11倍。生物相容性研究证明，SNEDDS制剂对巨噬细胞是安全的和相容的。体外细胞毒性实验表明，TMX-PAP-HA-ss-LCA SNEDDS对MCF-7乳腺癌细胞的杀伤作用明显优于TMX原药。与纯TMX相比，全身毒性研究证明了TMX-PAP-HA-ss-LCA的无毒性质。基于这些证据，TMX-PAP-HA-ss-LCA SNEDDS制剂似乎是一种有希望的粘液渗透、增强细胞内摄取的药物，具有很强的靶向抗增殖活性。(C)2020年由爱思唯尔出版。
The present study was intended to develop a papain grafted S-protected hyaluronic acid-lithocholic acid co-block (PAP-HA-ss-LCA) polymeric excipient as an amphiphilic muco permeating stabilizer for targeting breast cancer epithelial cells overexpressed with CD44 receptors. The mucopermeating, stabilizing and targeting capability of the PAP-HA-ss-LCA polymeric excipient was investigated by manufacturing tamoxifen (TMX) loaded self-nanoemulsifying drug delivery system (SNEDDS). TMX loaded PAP-HA-ss-LCA incorporated SNEDDS (TMX-PAP-HA-ss-LCA SNEDDS) were characterized for their surface chemistry, drug release, permeation enhancement, biocompatibility and antitumor activity. FFIR spectroscopic analysis showed successful synthesis of PAP-HA-ss-LCA polymer. X-ray diffraction (XRD) showed the amorphous form of TMX inside SNEDDS. The observed hydrodynamic diameter of TMX-PAP-HA-ss-LCA SNEDDS was 367.5 nm. Furthermore, Hyaluronic Acid-based Mucoadhesive Self Nanoemulsifying Drug Delivery System (SNEDDS) of TMX showed homogeneity in synthesis with low polydispersity and negative zeta potential due to stabilization with PAP-HA-ss-LCA polymer. The distinct spherical shape of the nanodroplets was evident by transmission electron microscopy (TEM). In vitro release kinetics indicated approximately >80% release within 48 h under sink conditions. Ex-vivo permeation study displayed 7.11-folds higher permeation of TMX by TMX-PAP-HA-ss-LCA in contrast to pure TMX. The biocompatibility study proved that SNEDDS formulation was safe and compatible against macrophages. In vitro cytotoxicity studies demonstrated that TMX-PAP-HA-ss-LCA SNEDDS could efficiently kill MCF-7 breast cancer cells as compared to the native TMX drug. Systemic toxicity studies proved the non-toxic nature of TMX-PAP-HA-ss-LCA in contrast to pure TMX. Based on these evidences, TMX-PAP-HA-ss-LCA SNEDDS formulation seems to be promising mucopermeating, augmented intracellular uptake with strong targeting potential for antiproliferative activity. (C) 2020 Published by Elsevier B.V.