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An injectable thiolated hyaluronate (HA-SH) hydrogel was developed as a stable in situ drug-releasing platform for tumor treatment. Biodegradable star-shaped polylactide (S-PLLA) formed porous microspheres encapsulating hydrophobic curcumin, then was blended with hydrophilic doxorubicin (Dox) and HA-SH precursor to yield Cur@S-PLLA/(Dox)HA-SH hydrogels. Microspheres reduced gelation time and increased mechanical strength. The dual-drug system enabled early Dox release and later Cur release after swelling or degradation, producing sustained tumor suppression, reduced MCF-7 viability, enhanced apoptosis (86.60% at 12 h), and cell-cycle blockade in phase M.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/fabrication-of-an-injectable-star-polylactidethiolated-hyaluronate-hydrogel-as-a-double-drug-delivery-system-for-cancer-treatment/385858/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/fabrication-of-an-injectable-star-polylactidethiolated-hyaluronate-hydrogel-as-a-double-drug-delivery-system-for-cancer-treatment/385858.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What was the main goal of the injectable HA-SH hydrogel system?","Question",{"text":113,"@type":114},"To create a stable, in situ drug-releasing platform that improves tumor treatment by addressing limitations such as poor penetration and rapid nanomaterial metabolism.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were the two drugs (doxorubicin and curcumin) incorporated into the hydrogel?",{"text":118,"@type":114},"Curcumin was encapsulated in porous microspheres made from star-shaped polylactide, and doxorubicin was blended with the microspheres and the HA-SH precursor to form a composite hydrogel.",{"name":120,"@type":111,"acceptedAnswer":121},"What release pattern did the double drug system achieve and why is it important?",{"text":122,"@type":114},"It released Dox early and then released Cur later after hydrogel swelling or S-PLLA degradation, aiming for long-lasting tumor suppression by inhibiting cancer cell survival.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},385858,1790359215,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","[http://pubs.acs.org/journal/acsodf](http://pubs.acs.org/journal/acsodf)  Article   \nFabrication of an Injectable Star-polylactide/Thiolated Hyaluronate Hydrogel as a Double Drug-Delivery System for Cancer Treatment  \nYifan Zhang, Min Fang, Zhiyi Tan, Yu-ang Zhang, Chun-yu Huang, * Lu Lu, Jinhuan Tian, Lihua Li, * and Changren Zhou  \n Cite This: ACS Omega 2023, 8, 16789−16799  \nRead Online  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n| ACCESS   | Metrics & More |  |  Article Recommendations |  | *sı Supporting Information |\n\nABSTRACT: Unsatisfactory solid-tumor penetration or rapid metabolism of nanomaterials limits their therapeutic efficacy. Here, we designed an injectable thiolated hyaluronate (HA-SH) hydrogel as a stable drugreleasing platform for in situ tumor treatment. Biodegradable star-shaped polylactide (S-PLLA) was first synthesized and fabricated to porous microspheres to encapsulate hydrophobic curcumin (Cur@S-PLLA), which was then blended with hydrophilic doxorubicin (Dox) and the HA-SH precursor to form composite in situ formable hydrogels [Cur@S-PLLA/(Dox)HA-SH]. The results showed that adding the microspheres improved the performance of the hydrogel, such as decreasing the gelation time from 1080 s to 960 s and also the swelling ratio. The mechanical strength increased from 27 to 45 kPa. In addition, the double drug system guaranteed a sustained release of drugs, releasing Dox at the early stage, with the continuous later release of Cur after gel swelling or S-PLLA degradation to achieve long-lasting tumor suppression, which inhibits the survival of cancer cells. The inhibitory effects of the hydrogels on MCF-7 were studied. The cell activity in the doubleloaded hydrogel was significantly lower than that of the control groups, and apparent dead cells appeared in 2 days and fewer living cells with time. Flow cytometry revealed that the Cur@S-PLLA/(Dox)HA-SH group had the highest apoptosis ratio of 86.60% at 12 h, and the drugs caused the cell cycle to be blocked in phase M to reduce cell division. In summary, the innovative release platform is expected to be used in long-lasting tumor suppression and provides more ideas for the design of drug carriers.  \n1. INTRODUCTION  \nCancer is a malignant tumor originating from the epithelial tissue. The corresponding treatment is divided into surgical treatment, chemotherapy, radiotherapy, and targeted therapy according to the different properties, tissues, organs, disease stages, and reactions. However, some treatments have specific side effects, and even after the tumors are removed surgically, residual cancer cells are also at risk of recurrence.1  \nDoxorubicin (Dox) and curcumin (Cur) are two of the common antitumor medicines for chemotherapy. Dox is an antitumor antibiotic that inhibits the synthesis of RNA and DNA.2 It is suitable for a wide variety of cancers, such as acute leukemia, breast cancer, malignant lymphoma, and so on.3 However, its efficacy is limited by dose-dependent cardiotoxicity, which affects the hematopoietic function of the bone marrow.4 Cur is a natural polyphenol found in the rhizome of some plants, has the properties of antitumor, anti-inflammatory, and anti-oxidation,5 and is pharmacologically safe even at high doses.6 It is well accepted that Cur inhibits tumor cell proliferation by blocking the activity of its transcription factor NF-κB and has several different molecular targets in the MAPK and PI3K/PKB’s signaling pathways to inhibit proliferation and induce apoptosis in vitro.7,8 Although Cur has numerous  \nadvantages, its therapeutic application is limited because of its poor aqueous solubility, low stability against alkaline pH conditions, extensive first-pass metabolism, and rapid systemic elimination.9  \nDirect drug administration will lead to varying drug concentrations in human bodies.10 Too high a local drug concentration of hydrophilic Dox can easily cause toxicity, and too low a concentration of hydrophobic Cur w","cbCaipsuhV9UfFOi","https://ap.wps.com/l/cbCaipsuhV9UfFOi","pdf",11268900,11,"English","# Abstract\n# Introduction\n## Limits of conventional cancer therapies\n## Doxorubicin and curcumin as chemotherapy agents\n## Role of drug carriers and hydrogels\n## Prior hydrogel and nanoplatform approaches","[{\"question\":\"What was the main goal of the injectable HA-SH hydrogel system?\",\"answer\":\"To create a stable, in situ drug-releasing platform that improves tumor treatment by addressing limitations such as poor penetration and rapid nanomaterial metabolism.\"},{\"question\":\"How were the two drugs (doxorubicin and curcumin) incorporated into the hydrogel?\",\"answer\":\"Curcumin was encapsulated in porous microspheres made from star-shaped polylactide, and doxorubicin was blended with the microspheres and the HA-SH precursor to form a composite hydrogel.\"},{\"question\":\"What release pattern did the double drug system achieve and why is it important?\",\"answer\":\"It released Dox early and then released Cur later after hydrogel swelling or S-PLLA degradation, aiming for long-lasting tumor suppression by inhibiting cancer cell survival.\"}]","Fabrication of an Injectable Star-polylactide/Thiolated Hyaluronate Hydrogel as a Double Drug-Delivery System for Cancer Treatment | PDF",1790271274,28]