Development of a novel solid lipid nanoparticles-loaded dual-reverse thermosensitive nanomicelle for intramuscular administration with sustained release and reduced toxicity

Abstract

To develop a novel solid lipid nanoparticles (SLNs)-loaded dual-reverse thermosensitive nanomicelle (DRTN) for intramuscular administration of flurbiprofen with sustained release and reduced toxicity, the DRTN was prepared with flurbiprofen-loaded SLNs, poloxamer 407 (P 407), poloxamer 188 (P 188) and water. Its rheological characterization, release, stability, pharmacokinetics and morphology were evaluated after intramuscular administration to rats. These SLNs were solid at 25 °C and transformed into liquid form at physiological temperature due to their melting point of about 32 °C. Furthermore, the DRTN retained a liquid state at 25 °C and gelled inside the body owing to its gelation temperature of about 34.7 °C, leading to an opposite reversible property of the SLNs. When compared to the hydrogel, it significantly decreased the drug release and exhibited a reduced initial fast release. It sustained a high plasma concentration for 60 h, which was significantly higher when compared to the suspension, indicating enhanced bioavailability. However, it showed a lower plasma concentration, AUC, and C_max values than that found for the hydrogel, suggesting the retarded release and decreased side effects of the drug. Unlike the hydrogel, it induced no injury to rat muscle as a result of no direct contact of the drug. It was stable for four months. Therefore, this novel DRTN system could be a strong candidate for the intramuscular administration of flurbiprofen.