{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:04:18Z","timestamp":1784657058067,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["SARChI"],"award-info":[{"award-number":["SARChI"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001325","name":"Cancer Association of South Africa","doi-asserted-by":"publisher","award":["CANSA"],"award-info":[{"award-number":["CANSA"]}],"id":[{"id":"10.13039\/501100001325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The present study aimed to design and develop a nanocomposite drug delivery system employing an antineoplastic-loaded antibody functionalized nanomicelle encapsulated within a Chitosan\u2013Poly(vinylpyrrolidone)\u2013Poly(N-isopropylacrylamide) (C\u2013P\u2013N) hydrogel to form an in situ forming implant (ISFI), responsive to temperature and pH for cancer cell-targeting following intraperitoneal implantation. The optimum nanomicelle formulation was surface-functionalized with anti-MUC 16 (antibody) for the targeted delivery of methotrexate to human ovarian carcinoma (NIH:OVCAR-5) cells in Athymic nude mice that expressed MUC16, as a preferential form of intraperitoneal ovarian cancer (OC) chemotherapy. The cross-linked interpenetrating C\u2013P\u2013N hydrogel was synthesized for the preparation of an in situ-forming implant (ISFI). Subsequently, the ISFI was fabricated by encapsulating a nanocomposite comprising of anti-MUC16 (antibody) functionalized methotrexate (MTX)-loaded poly(N-isopropylacrylamide)-b-poly(aspartic acid) (PNIPAAm-b-PASP) nanomicelles (AF(MTX)NM\u2019s) within the cross-linked C\u2013P\u2013N hydrogel. This strategy enabled specificity and increased the residence time of the nanomicelles at tumor sites over a period exceeding one month, enhancing uptake of drugs and preventing recurrence and chemo-resistance. Chemotherapeutic efficacy was tested on the optimal ovarian tumor-bearing Athymic nude mouse model and the results demonstrated tumor regression including reduction in mouse weight and tumor size, as well as a significant (p &lt; 0.05) reduction in mucin 16 levels in plasma and ascitic fluid, and improved survival of mice after treatment with the experimental anti-MUC16\/CA125 antibody-bound nanotherapeutic implant drug delivery system (ISFI) (p &lt; 0.05). The study also concluded that ISFI could potentially be considered an important immuno-chemotherapeutic agent that could be employed in human clinical trials of advanced, and\/or recurring, metastatic epithelial ovarian cancer (EOC). The development of this ISFI may circumvent the treatment flaws experienced with conventional systemic therapies, effectively manage recurrent disease and ultimately prolong disease-free intervals in ovarian cancer patients.<\/jats:p>","DOI":"10.3390\/ijms19103030","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T12:29:57Z","timestamp":1538656197000},"page":"3030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Chemotherapeutic Efficacy of Implantable Antineoplastic-Treatment Protocols in an Optimal Mouse Model for Human Ovarian Carcinoma Cell Targeting"],"prefix":"10.3390","volume":"19","author":[{"given":"Jonathan M.","family":"Pantshwa","sequence":"first","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"Rhoda","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Clift","sequence":"additional","affiliation":[{"name":"Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyamvada","family":"Pradeep","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-1529","authenticated-orcid":false,"given":"Yahya E.","family":"Choonara","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8640-4350","authenticated-orcid":false,"given":"Pradeep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa C.","family":"Du Toit","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clement","family":"Penny","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Division of Oncology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8119-3347","authenticated-orcid":false,"given":"Viness","family":"Pillay","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1006\/gyno.2002.6708","article-title":"Current status of the molecular characterization of the ovarian cancer antigen CA125 and implications for its use in clinical screening","volume":"88","author":"Whitehouse","year":"2003","journal-title":"J. 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