Blood-compatible, stable micelles of sodium alginate – Curcumin bioconjugate for anti-cancer applications

• Published in: European polymer journal Vol. 113; pp. 208 - 219
• Main Authors: Lachowicz, Dorota, Karabasz, Alicja, Bzowska, Monika, Szuwarzyński, Michał, Karewicz, Anna, Nowakowska, Maria
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2019; Elsevier BV
• Subjects: Anti-cancer activity; Biocompatibility; Bioconjugate; Blood; Brain; Breast cancer; Calcium ions; Cancer; Cells; Colon; Controlled release; Cross-linked micelles; Crosslinking; Curcumin; Cytotoxicity; Drug delivery systems; Endothelial cells; Micelles; Sodium alginate; Toxicity; Viability; Curcumin; Sodium alginate; Bioconjugate; Cross-linked micelles; Anti-cancer activity
• ISSN: 0014-3057; 1873-1945
• DOI: 10.1016/j.eurpolymj.2019.01.058

[Display omitted] •Conjugate of sodium alginate and curcumin was synthesized in easy one-step process.•Conjugate forms micelles already at the concentration slightly above 0.2 mg/ml.•Prolonged release of curcumin was achieved for physically cross-linked micelles.•Conjugate did not induce red cells aggregation, hemolysis or significant toxicity.•Dose dependent sensitivity of tested cancer cells to the conjugate was observed. The bioconjugate of alginate and curcumin (AA-CUR) was synthesized in a simple, one-step process and used to prepare the stable calcium cross-linked spherical micelles serving as a delivery vehicle for curcumin. Above its critical micelle concentration (0.6 mg/ml) AA-CUR forms colloidally stable micelles of ca. 200 nm. Prolonged, well controlled release of curcumin was observed from the AA-CUR micelles cross-linked with calcium ions for 5 h under the physiological conditions. To assess the safety of applying the bioconjugate into the bloodstream for possible anti-cancer applications, the interaction between AA-CUR and cells isolated from human blood was analyzed. No red cells aggregation or hemolysis was observed. AA-CUR was also shown to have no significant cytotoxicity to the human Peripheral Blood Mononuclear Cells (PBMC) isolated from peripheral blood of healthy donors and to the mouse primary brain endothelial cells. To evaluate the efficiency of the obtained bioconjugate in the anti-cancer therapy, the micellar solution of AA-CUR was tested against various cancer cells lines: mammary carcinoma 4T1, melanoma B16F10 and colon carcinoma CT26-CEA and MC38-CEA. The bioconjugate at the concentration of 0.7 mg/ml decreased the viability of cancer cells by ca. 80%. The cellular uptake of AA-CUR was rapid and the highest micelles accumulation was detected within 1 h after treatment. The AA-CUR micellar system can serve as an effective and safe delivery vehicle for curcumin.