Chitosan-Stearic Acid Based Polymeric Micelles for the Effective Delivery of Tamoxifen: Cytotoxic and Pharmacokinetic Evaluation.
Chitosan is a widely employed polysaccharide with positive zeta-potential and better tissue/cell adhesion. Its hydrophilicity, high viscosity, and insolubility at physiological pH are major hurdles in proper utilization of this macromolecule. Therefore, it was conjugated with biocompatible stearic acid and the conjugate was employed to develop polymeric micelles for delivery of tamoxifen to breast cancer cells. The conjugate was characterized by FT-IR and NMR, and the nanocarrier was characterized for micromeritics, surface charge, drug loading, and morphological attributes. The efficacy was evaluated by in vitro MTT studies, safety by erythrocyte compatibility, and biodistribution by in vivo pharmacokinetic studies. Despite better drug loading and sustained drug release, cytotoxicity on MCF-7 breast cancer cells was substantially enhanced and the pharmacokinetic profile was significantly modified. The AUC was enhanced manifolds along with reduced clearance. The findings are unique and provide an alternative to the conventional lipid-based nanocarriers for better dose delivery, tissue adhesion, and desired pharmacokinetic modulation.
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Kishangarh, Rajasthan, India, 305 817.
Nagarani
N
Thotakura
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Kishangarh, Rajasthan, India, 305 817.
Mukesh
M
Dadarwal
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Kishangarh, Rajasthan, India, 305 817.
Pramod
P
Kumar
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India, 160 014.
Gajanand
G
Sharma
Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu, India, 180001.
Santosh Kumar
SK
Guru
Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu, India, 180001.
Shashi
S
Bhushan
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Kishangarh, Rajasthan, India, 305 817. drkaisar@curaj.ac.in.
Kaisar
K
Raza
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India, 160 014.
Om Prakash
OP
Katare
D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008055:Lipids / Q000737:chemistry; D061986:MCF-7 Cells; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D017208:Rats, Wistar; D013229:Stearic Acids / Q000737:chemistry*; D013629:Tamoxifen / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000187:drug effects
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D008823:Micelles; D011108:Polymers; D013229:Stearic Acids; D013629:Tamoxifen; C031183:stearic acid; D048271:Chitosan
MCF-7 cells; MTT assay; bioadhesion; biodistribution; drug delivery