title: Folic acid functionalized long-circulating co-encapsulated docetaxel and curcumin solid lipid nanoparticles: In vitro evaluation, pharmacokinetic and biodistribution in rats.
abstract: The purpose of this study was to develop folic acid functionalized long-circulating co-encapsulated docetaxel (DTX) and curcumin (CRM) solid lipid nanoparticles (F-DC-SLN) to improve the pharmacokinetic and efficacy of DTX therapy. F-DC-SLN was prepared by hot melt-emulsification method and optimized by face centered-central composite design (FC-CCD). The SLN was characterized in terms of size and size distribution, drug entrapment efficiency and release profile. The cytotoxicity and cell uptake of the SLN formulations were evaluated in MCF-7 and MDA-MB-231 cell lines. The in vivo pharmacokinetic and biodistribution were studied in Wistar rats. F-DC-SLN exhibited 247.5 ± 3.40 nm particle size with 73.88 ± 1.08% entrapment efficiency and zeta potential of 14.53 ± 3.6 mV. Transmission electron microscopy (TEM) revealed spherical morphology of the SLN. Fluorescence microscopy confirmed the targeting efficacy of F-DC-SLN in MCF-7 cells. F-DC-SLN exhibited a significant increase in area under the curve (594.21 ± 64.34 versus 39.05 ± 7.41 μg/mL h) and mean residence time (31.14 ± 19.94 versus 7.24 ± 4.51 h) in comparison to Taxotere®. In addition, decreased DTX accumulation from F-DC-SLN in the heart and kidney in comparison to Taxotere may avoid to toxicity these vital organs. In conclusion, the F-DC-SLN improved the efficacy and pharmacokinetic profile of DTX exhibiting enhanced potential in optimizing breast cancer therapy.
authors.affiliation: a Department of Pharmaceutical Technology (Formulations) .
authors.forename: Harish
authors.initials: H
authors.lastname: Pawar
authors.affiliation: b Department of Pharmacology & Toxicology , and.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Surapaneni
authors.affiliation: b Department of Pharmacology & Toxicology , and.
authors.forename: Kulbhushan
authors.initials: K
authors.lastname: Tikoo
authors.affiliation: a Department of Pharmaceutical Technology (Formulations) .
authors.forename: Charan
authors.initials: C
authors.lastname: Singh
authors.affiliation: c Department of Pharmaceutical Technology (Process Chemistry) , National Institute of Pharmaceutical Education and Research (NIPER) , S.A.S. Nagar, Mohali, Punjab , India.
authors.forename: Rohani
authors.initials: R
authors.lastname: Burman
authors.affiliation: c Department of Pharmaceutical Technology (Process Chemistry) , National Institute of Pharmaceutical Education and Research (NIPER) , S.A.S. Nagar, Mohali, Punjab , India.
authors.forename: Manjinder Singh
authors.initials: MS
authors.lastname: Gill
authors.affiliation: a Department of Pharmaceutical Technology (Formulations) .
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel; D005492:Folic Acid; D003474:Curcumin
keywords: Cancer; curcumin; docetaxel; nanomedicine; solid lipid nanoparticles; targeted therapy