Rheological and Injectability Evaluation of Sterilized Poloxamer-407-Based Hydrogels Containing Docetaxel-Loaded Lipid Nanoparticles

Abstract

Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle–hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol–gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe–needle systems with acceptable force (2.2–13.4 N) and work (49.5–317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1–2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.

Keywords

• intratumoral administration
• injectable hydrogels
• nanocomposite hydrogels
• poloxamer
• lipid nanoparticles
• nanostructured lipid carriers (NLCs)