Comparison of in vivo behaviors of intramuscularly long-acting celecoxib nanosuspensions with different particle sizes for the postoperative pain treatment.

Celecoxib (CXB) has a good analgesic effect on postoperative acute pain, but clinically its compliance is compromised because of frequent administration. Therefore, the development of injectable celecoxib nanosuspensions (CXB-NS) for long-acting analgesic effects is highly desirable. However, how the particle size affects the in vivo behaviors of CXB-NS remains unclear. Herein, CXB-NS with different sizes were prepared by the wet-milling method. Following intramuscular (i.m.) injection in rats (50 mg/kg), all CXB-NS achieved sustained systemic exposure and long-acting analgesic effects. More importantly, CXB-NS showed size-dependent pharmacokinetic profiles and analgesic effects, and the smallest CXB-NS (about 0.5 µm) had the highest Cmax, T1/2, and AUC0-240h and the strongest analgesic effects on incision pain. Therefore, small sizes are preferred for long action by i.m. injection, and the CXB-NS developed in this study were alternative formulations for the treatment of postoperative acute pain.

Preparation and characterization of novel composite nanoparticles using zein and hyaluronic acid for efficient delivery of naringenin.

Hyaluronic acid (HA), a polymer mainly found in animal tissues, plays an important role in food research. In this study, it was used for delivery improvement of naringenin (NAR) by loading it into zein nanoparticles using an anti-solvent precipitation method. The optimal Nar/zein-HA nanoparticles were uniformly spherical with particle sizes of 209.2 ± 1.9 nm, polydispersity indexes of 0.146 ± 0.032 and zeta-potentials of -19.0 ± 0.7 mV. Moreover, the microstructure of Nar/zein-HA nanoparticles was maintained primarily by hydrophobic, electrostatic, and hydrogen-bonding interactions. Furthermore, Nar/zein-HA nanoparticles showed favorable physical stability and enhanced encapsulation efficiency. Additionally, the antioxidant capacity and release in simulated gastrointestinal digestion of Nar were significantly improved. Overall, these findings indicate that the delivery efficiency of Nar was improved by formulation of ternary nanoparticles.

Hydrophobic ion pairing-based self-emulsifying drug delivery systems: a new strategy for improving the therapeutic efficacy of water-soluble drugs.

INTRODUCTION: Self-emulsifying drug delivery systems (SEDDS) are formulations consisting of oil phase, emulsifiers, and co-emulsifiers, which can be spontaneously emulsified in the body to form O/W microemulsion. Traditionally, SEDDS are used commercially for the improvement of oral absorption and in vivo performances for poorly water-soluble drugs. However, SEDDS formulations were rarely reported for the delivery of water-soluble drugs. Recent studies have found that SEDDS have the potential for water-soluble macromolecular drugs by the application of the hydrophobic ion pairing (HIP) technology. AREAS COVERED: This review summarized the characteristics of HIP complexes in SEDDS and introduced their advantages and discussed the future prospects of HIP-based SEDDS in drug delivery. EXPERT OPINION: Hydrophobic ion pairing (HIP) is a technology that combines lipophilic structures on polar counterions to increase the lipophilicity through electrostatic interaction. Recent studies showed that HIP-based SEDDS offer an effective way to increase the mucosal permeability and improve the chemical stability for antibiotics, proteases, DNA-based drugs, and other water-soluble macromolecular drugs. It is believed that HIP-based SEDDS offer a potential and attractive method capable of delivering hydrophilic macromolecules with ionizable groups for oral administration.