title: Development, characterization and toxicological evaluations of phospholipids complexes of curcumin for effective drug delivery in cancer chemotherapy.
abstract: The purpose of this study was to prepare and characterize the complexes between curcumin (CU) phosphatidylcholine (PC) and hydrogenated soya phosphatidylcholine (HSPC) and to evaluate their anticancer activity. These CU-PC and CU-HSPC complexes (CU-PC-C and CU-HSPC-C) were evaluated for various physical parameters like Fourier transform infrared spectroscopy, melting point, solubility, scanning electron microscopy and the in vitro drug release study. These data confirmed the formation of phospholipids complexes. The in vitro hemolysis study showed that the complex was non-hemolytic. The anti-cancer potential of the complexes was demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay in MCF-7 cell line. This increase may be due to the amphiphilic nature of the complexes, which significantly enhances the water and lipid solubility of the CU. Unlike the free CU (which showed a total of only 90% drug release at the end of 8 h), complex showed around 40-60% release at the end of 8 h in dissolution studies. It showed that (when given in equimolar doses) complexes have significantly decreased the amount of CU available for absorption as compared with CU-free drug. Both CU-PC-C and CU-HSPC-C were found to be non-toxic at the dose equivalent to 2000 mg/kg of body weight of CU in the toxicity study. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A series of genotoxicity studies was conducted, which revealed the non-genotoxicity potential of the developed complexes. Thus, it can be concluded that the phospholipid complexes of CU may be a promising candidate in cancer therapy.
authors.affiliation: a Pharmaceutics Division and.
authors.forename: Renuka
authors.initials: R
authors.lastname: Khatik
authors.affiliation: a Pharmaceutics Division and.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dwivedi
authors.affiliation: a Pharmaceutics Division and.
authors.forename: Ankita
authors.initials: A
authors.lastname: Shukla
authors.affiliation: b Toxicology Division , CSIR - Central Drug Research Institute , Lucknow , Uttar Pradesh , India , and.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Srivastava
authors.affiliation: b Toxicology Division , CSIR - Central Drug Research Institute , Lucknow , Uttar Pradesh , India , and.
authors.forename: Srikanta Kumar
authors.initials: SK
authors.lastname: Rath
authors.affiliation: c Department of Pharmaceutical Sciences , Banasthali VidyaPeeth , Banasthali , Rajasthan , India.
authors.forename: Sarvesh Kumar
authors.initials: SK
authors.lastname: Paliwal
authors.affiliation: a Pharmaceutics Division and.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D010713:Phosphatidylcholines / Q000009:adverse effects / Q000737:chemistry; D010743:Phospholipids / Q000009:adverse effects* / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D010713:Phosphatidylcholines; D010743:Phospholipids; D003474:Curcumin
keywords: Anticancer; cell lines study; genotoxicity; in vitro