title: Evaluation of the antitumor effect of dexamethasone palmitate and doxorubicin co-loaded liposomes modified with a sialic acid-octadecylamine conjugate.
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.
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: 1414722049@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: 63230745@qq.com.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: 1589805010@qq.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: 584280744@qq.com.
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Lin
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: 925110883@qq.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: 717047745@qq.com.
authors.forename: Songlei
authors.initials: S
authors.lastname: Zhou
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: 1157379297@qq.com.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Su
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: pharmdeng@gmail.com.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D008081:Liposomes; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*
chemical_list: D000588:Amines; D008081:Liposomes; D003907:Dexamethasone; D004317:Doxorubicin; C009317:stearylamine; D019158:N-Acetylneuraminic Acid
keywords: Acetic acid (PubChem CID: 176); Acetonitrile (PubChem CID:6342); Antitumor; Cholesterol (PubChem CID: 5997); Co-loaded liposomes; Dexamethasone (PubChem CID:24893536); Dexamethasone palmitate; Dexamethasone palmitate (PubChem CID:63044); Doxorubicin; Doxorubicin HCl (PubChem CID: 443939); Ethanol (PubChem CID:702); N-hydroxy-succinimide (PubChem CID: 236334); Octadecylamine (PubChem CID:15793); Sialic acid (PubChem CID:906); Sialic acid–octadecylamine