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) andwater. 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.

Particle and Gel Characterization of Irinotecan-Loaded Double-Reverse Thermosensitive Hydrogel

“…Unlike the conventional hydrogel, this system was a dispersion that the thermosensitive hydrogel and the thermosensitive irinotecan-loaded solid lipid nanoparticles (SLN) maintained a liquid and solid form at 25 °C, respectively (Figure 1). Moreover, the former was changed to gel, and the latter was melted to liquid at 36.5 °C, respectively [18,19]. Numerous SLN dispersions and DRTHs were prepared with various amounts of ingredients, and their particle and gel properties were investigated.…”

“…Conventional hydrogel with excellent therapeutic effect is impossible to develop most particularly when incorporated with anti-tumour drugs such as irinotecan. It is because of their severe cytotoxic effects, which are more likely to occur due to their high initial drug release (burst effect) [18,19]. Thus, irinotecan-loaded double-reverse thermosensitive hydrogels (DRTHs) with controlled drug release are proposed for solving this problem.…”

Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration

“…This threshold was defined as a minimum gel strength at which none leaked out from the anus for 30 min after administration, resulting from a viscosity of approximately 4000 mPa s . Therefore, the gelation time, which was defined as the time required to convert from the flowing liquid to viscous gel, was determined as a time needed to attain 4000 mPa s of viscosity at 36.5 C. In this study, the gelation time of the DRTN was about 4.8 min (raw data not shown), indicating its speedy gelation (Din et al, 2015b).…”

“…The thermosensitive SLN dispersion consisted of irinotecan/lipid mixture/surfactant/water (1.15:0.5625:0.5625:77.25, weight ratio) showed high entrapment efficiency (almost 90%). The lipid blend of tricaprin and triethanolamine (8:2, weight ratio) with the melting point of approximately 32 C is solid at 25 C and melt at 36.5 C (Din et al, 2015b). Moreover, the mixture of Tween 80 and Span 20 at the weight ratio of 4:1 was used as surfactant.…”

Co‐encapsulating CoFe 2 O 4 and MTX for hyperthermia

“…Briefly, 10 µl of the sample was mixed with 1 ml of deionised water and vortexed for 2 min followed by analysis with zeta sizer. Each result displayed was measured in triplicate [34][35][36][37]. The size distribution of MRPCs showed two peaks, peak A corresponds to the average MRPCs of size 68.06 nm, and peak B indicates the presence of CoFe 2 O 4 nanoparticles that did not encapsulate ( Fig.…”