Evaluation of the antitumor effect of dexamethasone palmitate and doxorubicin co-loaded liposomes modified with a sialic acid-octadecylamine conjugate.
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| Abstract |
Dexamethasone palmitate has the potential to inhibit the activity of tumor-associated macrophages, which promote cancer proliferation, invasion, and metastasis; however, only very high and frequent doses are capable of inducing antitumor effects. With the aim to reduce the anticancer dose and decrease the nonspecific toxicity, we designed a liposomal system to co-deliver dexamethasone palmitate and doxorubicin. Furthermore, a ligand conjugate sialic acid-octadecylamine, with enhanced affinity towards the membrane receptors over-expressed in tumors, was anchored on the surface of the liposomes to increase drug distribution to the tumor tissue. Co-loaded liposomes were developed using lipid film hydration method to load dexamethasone palmitate and remote loading technology to load doxorubicin. The co-loaded liposomes modified with sialic acid-octadecylamine represented comparable physicochemical properties and blood plasma profiles with conventional co-loaded liposomes, but the biodistribution proved that sialic acid-octadecylamine modified liposomes accumulated more in tumor. The co-loaded liposomes showed higher tumor growth suppression than the single-drug loaded liposomes, while showing no additional drug toxicity in S180-bearing Kunming mice. The co-loaded liposomes modified with sialic acid-octadecylamine achieved a significantly better antitumor effect, and induced "shedding" of cancerous tissue in the mice. These finding suggested that co-loaded liposomes modified with sialic acid-octadecylamine provided a safe therapeutic strategy with outstanding anticancer activity.
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| Authors | Jing Sun, Yanzhi Song, Mei Lu, Xiangyun Lin, Yang Liu, Songlei Zhou, Yuqing Su, Yihui Deng |
| Journal | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 93 Pg. 177-83 (Oct 10 2016) ISSN: 1879-0720 [Electronic] Netherlands |
| PMID | 27539143 (Publication Type: Journal Article) |
| Copyright | Copyright © 2016 Elsevier B.V. All rights reserved. |
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