title: In vitro and in vivo evaluation of paclitaxel-lapatinib-loaded F127 pluronic micelles.
abstract: The aim of this study was to evaluate the in vitro and in vivo efficacy of paclitaxel-lapatinib-loaded Pluronic micelles. Lapatinib and pluronic sensitize the cancerous cells to paclitaxel via efflux pump inhibition. In addition, pluronic polymers can trigger intrinsic apoptosis pathways. Furthermore, micellar system can passively target the chemotherapeutic agents by enhanced permeability and retention effect. The paclitaxel-lapatinib-loaded micelles were characterized in means of encapsulation efficacy and size. The in vitro analyses were performed by MTT assay and uptake studies. Real-time imaging and in vivo anti-tumor efficacy studies were also performed. The prepared micelles have acceptable encapsulation ratio and size. Hemolysis assay confirmed that the micelles are hemo-compatible. MTT assay demonstrated that drug-loaded micelles have superior cytotoxicity compared with the naked drugs. The confocal microscopy and flowcytometry analyses showed that micelles are mainly internalized by endocytosis. According to the results of the in vivo imaging, the micelles are accumulated within liver. In vivo anti-tumor efficacy studies confirmed that tumor inhibition of drug-loaded micelles was significant compared to Intaxel®.
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|b Medical Biomaterials Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors: Pouya
authors: P
authors: Dehghankelishadi
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Ebrahim
authors: E
authors: Saadat
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Fatemeh
authors: F
authors: Ravar
authors: c Department of Biotechnology , Iranian Research Organization for Science and Technology , Tehran , Iran.
authors: Maliheh
authors: M
authors: Safavi
authors: d Department of Biochemistry , Institute of Biochemistry and Biophysics, University of Tehran , Tehran , Iran.
authors: Mahboobeh
authors: M
authors: Pordeli
authors: e Faculty of Pharmacy and Pharmaceutical Sciences Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors: Mehdi
authors: M
authors: Gholami
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|b Medical Biomaterials Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors: Farid Abedin
authors: FA
authors: Dorkoosh
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology; D000077341:Lapatinib; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000378:metabolism; D020442:Poloxamer / Q000008:administration & dosage* / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D047368:Tumor Burden / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D008823:Micelles; D011799:Quinazolines; D000077341:Lapatinib; D020442:Poloxamer; D017239:Paclitaxel
keywords: Efflux pump inhibition; chemotherapeutics; combined drug delivery; enhanced permeability and retention; multidrug resistance