Evaluation of the antitumor effect of dexamethasone palmitate and doxorubicin co-loaded liposomes modified with a sialic acid-octadecylamine conjugate

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• 作者：Jing Sun ^{1414722049@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Yanzhi Song ^{63230745@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Mei Lu ^{1589805010@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Xiangyun Lin ^{584280744@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Yang Liu ^{925110883@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Songlei Zhou ^{717047745@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Yuqing Su ^{1157379297@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Yihui Deng ; ^{pharmdeng@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Doxorubicin HCl (PubChem CID ; 443939) ; Dexamethasone palmitate (PubChem CID ; 63044) ; Dexamethasone (PubChem CID ; 24893536) ; Octadecylamine (PubChem CID ; 15793) ; Sialic acid (PubChem CID ; 906) ; Acetonitrile (PubChem CID ; 6342) ; Ethanol (PubChem CID ; 702) ; Cholesterol (PubChem CID ; 5997) ; Acetic acid (PubChem CID ; 176) ; N-hydroxy-succinimide (PubChem CID ; 236334)
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：10 October 2016
• 年：2016
• 卷：93
• 期：Complete
• 页码：177-183
• 全文大小：998 K

文摘

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.