1. Encapsulating paclitaxel in polymeric nanomicelles increases antitumor activity and prevents peripheral neuropathy.
- Author
-
Oda CMR, Silva JO, Fernandes RS, Braga AV, Machado RR, Coelho MM, Cassali GD, Reis DC, de Barros ALB, and Leite EA
- Subjects
- Animals, Antineoplastic Agents, Phytogenic chemical synthesis, Antineoplastic Agents, Phytogenic toxicity, Cell Line, Tumor, Dose-Response Relationship, Drug, Drug Carriers chemical synthesis, Drug Carriers toxicity, Female, Mice, Mice, Inbred BALB C, Nanoparticles chemistry, Nanoparticles toxicity, Paclitaxel chemical synthesis, Paclitaxel toxicity, Peripheral Nervous System Diseases chemically induced, Polymers administration & dosage, Polymers chemical synthesis, Tumor Burden drug effects, Tumor Burden physiology, Xenograft Model Antitumor Assays methods, Antineoplastic Agents, Phytogenic administration & dosage, Drug Carriers administration & dosage, Micelles, Nanoparticles administration & dosage, Paclitaxel administration & dosage, Peripheral Nervous System Diseases prevention & control
- Abstract
Paclitaxel (PTX) has a great clinical significance as an antitumor drug, although several side effects are strongly dose-limiting. In this way, we prepared a PTX-loaded 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] polymeric micelles (PM/PTX) in an attempt to improve safety and effectiveness of conventional PTX formulation (CrEL/EtOH/PTX). In this study, we evaluated from both formulations: stability after dilution, hemocompatibility, cellular uptake, acute toxicity in healthy mice, antitumor activity, and toxicity after multiple-dose treatment. PM/PTX appeared to be more stable than CrEL/EtOH/PTX after dilution. PM/PTX did not exhibit hemolytic activity (values <1%), even at high concentrations. In vitro cellular uptake study indicated that polymeric micelles were able to deliver more PTX (5.8 %) than CrEL/EtOH (2.7 %) to 4T1 cells. In the acute toxicity evaluation in healthy mice, CrEL/EtOH/PTX (single dose of 20 mg/kg) induced peripheral neuropathy, which was not observed in PM/PTX group. Similar results were observed after tumor-bearing mice received a multiple-dose regimen (seven doses of 10 mg/kg). Worth mentioning, we also evaluated vehicles, and CrEL/EtOH alone was not capable of inducing neuropathic pain. Besides, PM/PTX exhibited a higher antitumor activity with an inhibition ratio approximately 1.5-fold higher than CrEL/EtOH/PTX group. This study suggested that PM/PTX is safer than CrEL/EtOH/PTX, and was able to improve the antitumor effectiveness in a 4T1 breast cancer model., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF