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Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma
Zhang J.1; Zhang M.4; Ji J.2; Fang X.3; Pan X.2; Wang Y.1; Wu C.2; Chen M.1
2015-10-26
Source PublicationPharmaceutical Research
ISSN1573904X 07248741
Volume32Issue:10Pages:3376-3390
AbstractPurpose: The major hurdle of current drug carrier against hepatocellular carcinoma (HCC) is the lack of specific and selective drug delivery to HCC. In this study, a novel glycyrrhetinic acid (GA) and poly(L-Histidine) (PHIS) mediated polymeric drug delivery system was developed to target HCC that have GA binding receptors and release its encapsulated anticancer drug in the acidic microenvironment of HCC. Methods: Firstly, GA and PHIS were conjugated to form poly (ethylene glycol)-poly(lactic-co-glycolic acid) (GA-PEG-PHIS-PLGA, GA-PPP) micelles by grafting reaction between active terminal groups. Secondly, andrographolide (AGP) was encapsulated to GA-PPP to make AGP/GA-PPP using the solvent evaporation method. The pH-responsive property of AGP/GA-PPP micelles was validated by monitoring its stability and drug release behavior in different pH conditions. Furthermore, selective hepatocellular uptake of GA-PPP micelles in vitro, liver specific drug accumulation in vivo, as well as the enhanced antitumor effects of AGP/GA-PPP micelles confirmed the HCC targeting property of our novel drug delivery system. Results: Average size of AGP/GA-PPP micelles increased significantly and the encapsulated AGP released faster in vitro at pH 5.0, while micelles keeping stable in pH 7.4. AGP/GA-PPP micelles were uptaken more efficiently by human Hep3B liver cells than that by human MDA-MB-231 breast cancer cells. GA-PPP micelles accumulated specifically in the liver and possessed long retention time in vivo. AGP/GA-PPP micelles significantly inhibited tumor growth and provided better therapeutic outcomes compared to free AGP and AGP/PEG-PLGA(AGP/PP) micelles without GA and PHIS decoration. Conclusions: This novel GA-PPP polymeric carrier is promising for targeted treatment of HCC. [Figure not available: see fulltext.]
Keywordandrographolide glycyrrhetinic acid hepatocellular carcinoma micelles pH-sensitive
DOI10.1007/s11095-015-1714-2
URLView the original
Language英語
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Cited Times [WOS]:28   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.University of Macau
2.Sun Yat-Sen University
3.University of Florida
4.South China University of Technology
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Zhang J.,Zhang M.,Ji J.,et al. Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma[J]. Pharmaceutical Research,2015,32(10):3376-3390.
APA Zhang J..,Zhang M..,Ji J..,Fang X..,Pan X..,...&Chen M..(2015).Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma.Pharmaceutical Research,32(10),3376-3390.
MLA Zhang J.,et al."Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma".Pharmaceutical Research 32.10(2015):3376-3390.
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