curcumin and stearylamine

We aim to prepare a size-shifting nanocarrier for site-targeting mucosal drug delivery that can penetrate through mucus gel layer and remain close to the absorption membrane. As nanocarriers can be engineered to penetrate mucus but they can also back diffuse into outer mucus regions, a size shifting to micron range once they have reached the absorption membrane would prevent back-diffusion effect and extend drug release over a long period of time. For this purpose, we loaded solid lipid nanoparticles (SLN) with a phosphate ester surfactant and octadecylamine. Alkaline phosphatase (AP), a membrane bound enzyme was for the first time utilized as an in situ partner for triggering the size conversion at epithelial cell surface. Having the size of ~120 nm, SLN with hydrophilic and phosphate-decorated shells were shown to penetrate through mucus gel and form aggregates above cell layer surface. Aggregates of 5-8 µm were formed due to interparticle interactions induced by enzymatic phosphate removal after ~30 min in contact with isolated AP. The developed SLN system could be a potential tool for mucosal drug delivery to AP-expressing tissues like colon, lung, cervix, vagina and some mucus-secreting tumors.

Topics: Administration, Mucosal; Alkaline Phosphatase; Amines; Animals; Caco-2 Cells; Curcumin; Drug Carriers; Drug Liberation; Humans; Hydrophobic and Hydrophilic Interactions; Lipids; Mucus; Nanoparticles; Particle Size; Surface-Active Agents; Sus scrofa

At present, the chemotherapy of advanced inoperable liver cancer is limited with serious side effects. Curcumin possesses multiple cancer preventive activities and low safety concerns. However, its poor solubility and instability in water pose significant pharmacological barriers to its clinical application. In this study, we presented a novel delivery system - the glycyrrhetinic acid modified curcumin-loaded cationic liposomes (GAMCLCL) and investigated its antitumor activities on HepG2 cells in vitro and in H22 tumor-bearing mice. The experimental results demonstrated that GAMCLCL was a cationic liposome and could be Intravenous administration. Compared to free curcumin, GAMCLCL exhibited stronger antitumor activities in vitro and in vivo. The antitumor results of GAMCLCL after intravenous administration were very similar to those after intratumoral administration. The main activities of GAMCLCL and curcumin included inhibition of HepG2 cell proliferation, inhibition of tumor growth, reduction of tumor microvascular density, down-regulation of the expression of VEGF protein, and up-regulation of the expression of Caspases3 protein in H22 tumor tissues. Furthermore, GAMCLCL improved the parameters of WBC, RBC, ALT, CRE, LDH of H22 tumor-bearing mice. Curcumin is a nontoxic natural compound with definite antitumor activities, its antitumor effects can be enhanced by preparation of GAMCLCL.

Topics: Amines; Animals; Antineoplastic Agents; Apoptosis; Cations; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Drug Carriers; Erythrocytes; Glycyrrhetinic Acid; Hemolysis; Hep G2 Cells; Humans; Liposomes; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred Strains; Tissue Distribution; Xenograft Model Antitumor Assays