Natural lipids enriched self-nano-emulsifying systems for effective co-delivery of tamoxifen and naringenin: Systematic approach for improved breast cancer therapeutics.
The nano-miceller drug delivery carriers of tamoxifen (TMX) having natural ingredients like polyunsaturated fatty acid (PUFA) with self-nano-emulsifying properties was developed with naringenin (NG) in a synergistic manner i.e. TMX-NG-SNEDDS. The optimized nano-formulation revealed complete drug release in 30 min and >80% permeation in 45 min. Superior cellular uptake potential (4.6-6.5-fold) of the TMX-NG-SNEDDS using Caco-2 cells while cytotoxicity study on MCF-7 cells indicated significant results (P<0.05) of TMX-NG-SNEDDS. The in vivo pharmacokinetic study also construed remarkable improvement (7.3 and 11.4-fold increase in Cmaxand AUC) in rate of drug absorption and 2-fold reduction in Tmaxby optimized TMX-NG-SNEDDS. In vivo DMBA model construed superior efficacy of the formulation by reducing tumor size, and improved survival rate of the animals justifies its safety aspect as well.
UGC Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University, Chandigarh, India 160 014; University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies Panjab University, Chandigarh, India 160 014. Electronic address: premjeetsandhu27@gmail.com.
Premjeet Singh
PS
Sandhu
UGC Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University, Chandigarh, India 160 014.
Rajendra
R
Kumar
University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies Panjab University, Chandigarh, India 160 014.
Sarwar
S
Beg
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India 160062.
Sanyog
S
Jain
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India 160062.
Varun
V
Kushwah
University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies Panjab University, Chandigarh, India 160 014.
O P
OP
Katare
UGC Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University, Chandigarh, India 160 014; University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies Panjab University, Chandigarh, India 160 014. Electronic address: bsbhoop@pu.ac.in.
Bhupinder
B
Singh
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy*; D018938:Caco-2 Cells; D016503:Drug Delivery Systems; D004655:Emulsions; D044950:Flavanones / Q000008:administration & dosage*; D006801:Humans; D008055:Lipids / Q000627:therapeutic use*; D013629:Tamoxifen / Q000008:administration & dosage*
D018931:Antineoplastic Agents, Hormonal; D004655:Emulsions; D044950:Flavanones; D008055:Lipids; D013629:Tamoxifen; C005273:naringenin
Apoptosis; Bioavailability; DMBA-model; Nano-micelles; P-gp-inhibitors