Nanoformulation Development to Improve the Biopharmaceutical Properties of Fisetin Using Design of Experiment Approach.

This study aimed to design an effective nanoparticle-based carrier for the oral delivery of fisetin (FST) with improved biopharmaceutical properties. FST-loaded nanoparticles were prepared with polyvinyl alcohol (PVA) and poly(lactic-co-glycolic acid) (PLGA) by the interfacial deposition method. A central composite design of two independent variables, the concentration of PVA and the amount of PLGA, was applied for the optimization of the preparative parameter. The responses, including average particle size, polydispersity index, encapsulation efficiency, and zeta potential, were assessed. The optimized formulation possessed a mean particle size of 187.9 nm, the polydispersity index of 0.121, encapsulation efficiency of 79.3%, and zeta potential of -29.2 mV. The morphological observation demonstrated a globular shape for particles. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that the encapsulated FST was presented as the amorphous state. The dissolution test indicated a 3.06-fold increase for the accumulating concentrations, and the everted gut sac test showed a 4.9-fold gain for permeability at the duodenum region. In conclusion, the optimized FST-loaded nanoparticle formulation in this work can be developed as an efficient oral delivery system of FST to improve its biopharmaceutic properties.

Formulation Approaches to Crystalline Status Modification for Carotenoids: Impacts on Dissolution, Stability, Bioavailability, and Bioactivities.

Carotenoids, including carotenes and xanthophylls, have been identified as bioactive ingredients in foods and are considered to possess health-promoting effects. From a biopharmaceutical perspective, several physicochemical characteristics, such as scanty water solubility, restricted dissolution, and susceptibility to oxidation may influence their oral bioavailability and eventually, their effectiveness. In this review, we have summarized various formulation approaches that deal with the modification of crystalline status for carotenoids, which may improve their physicochemical properties, oral absorption, and biological effects. The mechanisms involving crystalline alteration and the typical methods for examining crystalline states in the pharmaceutical field have been included, and representative formulation approaches are introduced to unriddle the mechanisms and effects more clearly.

Poly (Lactic-Co-Glycolic) Acid-Poly (Vinyl Pyrrolidone) Hybrid Nanoparticles to Improve the Efficiency of Oral Delivery of ß-Carotene.

The aim of this study was to develop a nanoparticle formulation made of poly (vinyl pyrrolidone) (PVP) and poly (lactic-co-glycolic) acid (PLGA) for the oral delivery of ß-carotene (BC). The hybrid nanoparticles were prepared by the interfacial deposition method, and the physicochemical properties of this formulation were characterized in terms of its morphology, particle size, size distribution, encapsulation efficiency, dissolution, intestinal permeability, and in vivo pharmacokinetics. Our results demonstrated that BC-loaded nanoformulation and PLGA nanoparticles (PNP) significantly enhanced a release 6.1 times higher than BC suspension. The fortification of PVP into PLGA nanoparticles, named PLGA-PVP hybrid nanoparticles (PPNP), significantly reduced the particle size, as well as led to an increase 1.9 times higher in the in vitro release of BC, compared with PNP. For the ex vivo intestinal permeability assessment, PNP and PPNP-K15 significantly enhanced the intestinal permeability by 2.7 and 6.5 times at the jejunum, and 2.3 and 4.5 times at the ileum, when compared with unformulated BC. According to the pharmacokinetic study, the optimized hybrid formulation significantly increased the peak plasma concentration (Cmax) and the area under the curve (AUC0-t), and the oral relative bioavailability showed a five-fold enhancement compared with that of the BC suspension. Our results indicate that the hybrid nanoparticulate delivery system is an efficient strategy for the oral delivery of BC.

Self-Emulsifying Phospholipid Preconcentrates for the Enhanced Photoprotection of Luteolin.

Exposure to ultraviolet B (UVB) leads to the overproduction of reactive oxygen species (ROS), causing higher risks of skin disorders. Luteolin (Lut) is a naturally occurring antioxidant that can absorb a broad range of ultraviolet light, but its water solubility and skin permeability are limited and insufficient. The aim of the current study was to develop a Lut-loaded self-emulsifying phospholipid preconcentrate (LSEPP) for enhancing the solubility, permeability, and photoprotective activity of Lut. The designed formulations were firstly examined for their droplet size, zeta potential, dispersity, and in vitro corneum permeability after dispensing the preconcentrate to form an emulsion; the optimized formulation was further characterized for its emulsified morphology, compatibility with excipients, stability in the preconcentrate form, and photoprotective activity by the HaCaT cell model under the emulsified status. The optimized LSEPP formulation attained a smaller droplet size (140.6 ± 24.2 nm) with the addition of 1,8-cineole and increased the permeability of Lut by 7-fold. As evidenced in the cell model studies, the optimized LSEPP formulation can efficiently deliver Lut into HaCaT cells after emulsification and result in a 115% better cell viability as well as a 203% stronger ROS scavenging capability, compared with those of unformulated Lut after UVB irradiation. To sum up, we have successfully developed an LSEPP formulation, which is a safe and promising topical delivery system for enhancing the photoprotective effects of Lut.

Blood-to-muscle distribution and urinary excretion of higenamine in rats.

Higenamine is a ß2 -agonist that has been prohibited in sports by the World Anti-Doping Agency. Higenamine could potentially promote anabolism and lipolysis; however, its crucial pharmacokinetics data, particularly muscle distribution, remain unavailable. The present study aims to investigate the blood-to-muscle distribution as well as the urinary excretion of higenamine in laboratory rats. In the first experiment, the microdialysis technique was employed to continuously measure free, protein-unbound concentrations in blood and muscle for 90 min (sampling at a 5-min interval) after rats received IV infusion of higenamine. The mean half-lives of higenamine in blood and muscle were 17.9 and 19.0 min, respectively. The blood-to-muscle distribution ratio (AUCmuscle /AUCblood ) of higenamine was estimated to be 22%. In the second experiment, rats were orally administered with a single-dose higenamine, and their urine samples were profiled at a 12-h interval for up to 48 h. Results showed only a small portion of total consumption (1.44%, ranging 0.71%-2.50%) was excreted in the urine. Among these time points, about 43% cumulative amount of higenamine was eliminated within the first 12 h. Our data suggested that one-quarter of the unbound higenamine rapidly penetrates from the vessels into muscle, distributes to the interstitial fluid, then eliminates from the rat in a short span of time. The muscle tissue is likely to have a low binding affinity for higenamine, and renal excretion plays a minor role in its elimination. Together, our findings provide valuable pharmacokinetics data that may gain deeper insights into higenamine's role in skeletal muscle functions.