title: C60-fullerenes for delivery of docetaxel to breast cancer cells: A promising approach for enhanced efficacy and better pharmacokinetic profile.
abstract: Docetaxel has always attracted the researchers owing to its promises and challenges. Despite marked efficacy, concerns like poor aqueous solubility, lower bioavailability, poor tissue penetration and dose related side-effects offer further scope of research on docetaxel. The present study aims to explore the potential of C60-fullerenes in the delivery of docetaxel to cancerous cells. C60-fullerenes were carboxylated, acylated and conjugated with the drug. The chemical processes were monitored by UV, FT-IR and NMR spectroscopy. The conjugate was further characterized for drug loading, micromeritics, drug release, morphology and evaluated for in-vitro cytotoxicity, haemolysis and in-vivo pharmacokinetic profile. The developed nanoconstruct was able to enhance the bioavailability of docetaxel by 4.2 times and decrease the drug clearance by 50%. The developed system was able to control the drug release and was found to be compatible with erythrocytes. The cytotoxic potential on studied MCF-7 and MDA-MB231 cell lines was also enhanced by many folds, indicating marked promise in efficacy enhancement and dose reduction. The present findings are encouraging and offer a technique to enhance the delivery and efficacy potential of anticancer agents, especially belonging to BCS class IV.
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan 305817, India. Electronic address: razakaisar_pharma@yahoo.co.in.
authors.forename: Kaisar
authors.initials: K
authors.lastname: Raza
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan 305817, India.
authors.forename: Nagarani
authors.initials: N
authors.lastname: Thotakura
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan 305817, India.
authors.forename: Pramod
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan 305817, India.
authors.forename: Mayank
authors.initials: M
authors.lastname: Joshi
authors.affiliation: Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Lovely Faculty of Applied Medical Sciences, Lovely Professional University, Jalandhar, Punjab 144806, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Bhatia
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan 305817, India.
authors.forename: Vipin
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan 305817, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Malik
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Gajanand
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Guru
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: O P
authors.initials: OP
authors.lastname: Katare
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017209:Apoptosis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D037741:Fullerenes / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D008657:Metabolic Clearance Rate; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D037741:Fullerenes; D043823:Taxoids; D000077143:Docetaxel; C069837:fullerene C60
keywords: Bioavailability enhancement; Buckminsterfullerene; Drug clearance; Drug delivery; Enhanced cytotoxicity; MCF-7; MDA-MB-231; One compartment open body model