Rhodojaponin III-Loaded Chitosan Derivatives-Modified Solid Lipid Nanoparticles for Multimodal Antinociceptive Effects in vivo

Abstract

Background Rhodojaponin III (RJ-III) is a bioactive diterpenoid, which is mainly found in Rhododendron molle G. Don (Ericaceae), a potent analgesia in traditional Chinese medicine with several years of clinical applications in the country. However, its clinical use is limited by its acute toxicity and poor pharmacokinetic profiles. To reduce such limitations, the current study incorporated RJ-III into the colloidal drug delivery system of hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (SLNs) to improve its sustained release and antinociceptive effects in vivo for oral delivery. Results The optimized RJ-III@HACC-SLNs were close to spherical, approximately 134 nm in size, and with a positive zeta potential. In vitro experiments showed that RJ-III@HACC-SLNs were stable in the simulated gastric fluid and had a prolonged release in PBS (pH = 6.8). Pharmacokinetic results showed that after intragastric administration in mice, the relative bioavailability of RJ-III@HACC-SLNs was 87.9%. Further, it was evident that the peak time, half-time, and mean retention time of RJ-III@HACC-SLNs were improved than RJ-III after the administration. In addition, pharmacodynamic studies revealed that RJ-III@HACC-SLNs markedly reduced the acetic acid, hot, and formalin-induced nociceptive responses in mice ( P < 0.001), and notably increased the analgesic time ( P < 0.01). Moreover, RJ-III@HACC-SLNs not only showed good biocompatibility with Caco-2 cells in vitro but its LD 50 value was also increased by 1.8-fold as compared with that of RJ-III in vivo. Conclusion These results demonstrated that RJ-III@HACC-SLNs improved the pharmacokinetic characteristics of the RJ-III, thereby exhibiting toxicity-attenuating potential and antinociceptive enhancing properties. Consequently, HACC-SLNs loaded with RJ-III could become a promising oral formulation for pain management that deserves further investigation in the future.

Hydrogel armed with Bmp2 mRNA-enriched exosomes enhances bone regeneration

“…Lipid carriers have become the main RNA delivery vehicles [ 48 ]. However, because lipid nanoparticles may be toxic to cells and stimulate the release of systemic inflammatory cytokines, there is increasing interest in natural transporters such as exosomes [ 49 ]. Nearly 20 years after liposomes were first created, scientists have discovered exosomes in most eukaryotic cells, which may play important roles in intercellular communication and signalling, as well as in the transport of proteins, lipids, and nucleic acids between cells.…”

Nanostructures in Chinese herbal medicines (CHMs) for potential therapy

“…RJ-III loaded into hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (RJ-III@HACC-SLNs) has a lower toxicity and higher peak time and half-time than free RJ-III. 81 3.2.2 Enhancement of target specificity. Liposomes have been extensively applied as drug delivery agents, particularly for targeted therapy.…”

“…RJ-III loaded into hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (RJ-III@HACC-SLNs) has a lower toxicity and higher peak time and half-time than free RJ-III. 81…”

Quantification of Rhodojaponin II and Rhodojaponin III in Rat Plasma by Ultra‐Performance Liquid Chromatography‐Tandem Mass Spectrometry

“…Notably, Rhodojaponin III surpasses morphine in terms of acute pain models as well as inflammatory pain models. Its potency for diabetic neuropathic pain models is 100 times greater than gabapentin's effectiveness [ 2 , 7 ]. However, it was discovered that both intraperitoneal administration and oral consumption of Rhodojaponin III resulted in severe acute toxicity in mice.…”