title: One-step formation of lipid-polyacrylic acid-calcium carbonate nanoparticles for co-delivery of doxorubicin and curcumin.
abstract: A doxorubicin (Dox) and curcumin (Cur) combination treatment regimen has been widely studied in pre-clinical research. However, the nanoparticles developed for this combination therapy require a consecutive drug loading process because of the different water-solubility of these drugs. This study provides a strategy for the "one-step" formation of nanoparticles encapsulating both Dox and Cur. We took advantage of polyacrylic acid (PAA) and calcium carbonate (CaCO3) to realise a high drug entrapment efficiency (EE) and pH-sensitive drug release using a simplified preparation method. Optimisation of lipid ratios and concentrations of CaCO3was conducted. Under optimal conditions, the mean diameter of PEGylated lipid/PAA/CaCO3nanoparticles with encapsulated Cur and Dox (LPCCD) was less than 100 nm. An obvious pH-sensitive release of both drugs was observed, with different Dox and Cur release rates. Successful co-delivery of Cur and Dox was achieved via LPCCD on HepG2 cells. LPCCD altered the bio-distribution of Dox and Cur in vivo and decreased Dox-induced cardiotoxicity. The current investigation has developed an efficient ternary system for co-delivery of Dox and Cur to tumours, using a "one-step" formation resulting in nanoparticles possessing remarkable pH-sensitive drug release behaviour, which may be valuable for further clinical studies and eventual clinical application.
authors.affiliation: a Graduate School of Biomedical Sciences , Nagasaki University , Nagasaki , Japan.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Peng
authors.affiliation: a Graduate School of Biomedical Sciences , Nagasaki University , Nagasaki , Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.affiliation: a Graduate School of Biomedical Sciences , Nagasaki University , Nagasaki , Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: b Department of Pharmaceutics , China Pharmaceutical University , Nanjing , PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: a Graduate School of Biomedical Sciences , Nagasaki University , Nagasaki , Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Kuroda
authors.affiliation: a Graduate School of Biomedical Sciences , Nagasaki University , Nagasaki , Japan.
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D002119:Calcium Carbonate / Q000737:chemistry*; D003474:Curcumin / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D056945:Hep G2 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000180:Acrylic Resins; D008055:Lipids; C006903:carbopol 940; D004317:Doxorubicin; D002119:Calcium Carbonate; D003474:Curcumin
keywords: Doxorubicin; calcium carbonate; curcumin; lipid nanoparticle; polyacrylic acid