{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:40:44Z","timestamp":1776292844551,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T00:00:00Z","timestamp":1576195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004686","name":"Deanship of Scientific Research, King Faisal University","doi-asserted-by":"publisher","award":["180009"],"award-info":[{"award-number":["180009"]}],"id":[{"id":"10.13039\/501100004686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Selective targeting of anticancer drugs to the tumor site is beneficial in the pharmacotherapy of hepatocellular carcinoma (HCC). This study evaluated the prospective of galactosylated chitosan nanoparticles as a liver-specific carrier to improve the therapeutic efficacy of gemcitabine in HCC by targeting asialoglycoprotein receptors expressed on hepatocytes. Nanoparticles were formulated (G1\u2013G5) by an ionic gelation method and evaluated for various physicochemical characteristics. Targeting efficacy of formulation G4 was evaluated in rats. Physicochemical characteristics exhibited by nanoparticles were optimal for administering and targeting gemcitabine effectively to the liver. The biphasic release behavior observed with G4 can provide higher drug concentration and extend the pharmacotherapy in the liver target site. Rapid plasma clearance of gemcitabine (70% in 30 min) from G4 was noticed in rats with HCC as compared to pure drug (p &lt; 0.05). Higher uptake of gemcitabine predominantly by HCC (64% of administered dose; p &lt; 0.0001) demonstrated excellent liver targeting by G4, while mitigating systemic toxicity. Morphological, biochemical, and histopathological examination as well as blood levels of the tumor marker, alpha-fetoprotein, in rats confirmed the curative effect of G4. In conclusion, this study demonstrated site-specific delivery and enhanced in vivo anti-HCC efficacy of gemcitabine by G4, which could function as promising carrier in hepatoma.<\/jats:p>","DOI":"10.3390\/molecules24244566","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T11:27:22Z","timestamp":1576236442000},"page":"4566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Development of Asialoglycoprotein Receptor-Targeted Nanoparticles for Selective Delivery of Gemcitabine to Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2850-8669","authenticated-orcid":false,"given":"Anroop B.","family":"Nair","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-528X","authenticated-orcid":false,"given":"Jigar","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2684-4186","authenticated-orcid":false,"given":"Bandar E.","family":"Al-Dhubiab","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snehal S.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6752-9094","authenticated-orcid":false,"given":"Mohamed A.","family":"Morsy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"},{"name":"Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-0159","authenticated-orcid":false,"given":"Vimal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5812-3412","authenticated-orcid":false,"given":"Vishal","family":"Chavda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-6673","authenticated-orcid":false,"given":"Shery","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2058-255X","authenticated-orcid":false,"given":"Nagaraja","family":"Sreeharsha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4245-0803","authenticated-orcid":false,"given":"Pottathil","family":"Shinu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7007-9119","authenticated-orcid":false,"given":"Mahesh","family":"Attimarad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-1549","authenticated-orcid":false,"given":"Katharigatta N.","family":"Venugopala","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"},{"name":"Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4000, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"907","DOI":"10.4254\/wjh.v9.i21.907","article-title":"Chemotherapy for hepatocellular carcinoma: The present and the future","volume":"9","author":"Biagini","year":"2017","journal-title":"World J. 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