Search

Lyotropic nonlamellar liquid crystalline nanoparticles (NPs) (LCN), such as cubosomes and hexosomes, are useful tools for applications in drug delivery because of their unique structural properties. LCNs are highly versatile carriers that can be applied for use with topical, oral, and intravenous treatments. In recent years, significant research has focused on improving their preparation and characterization, including controlling drug release and enhancing the efficacy of loaded bioactive molecules. Nevertheless, the clinical translation of LCN-based carriers has been slow. In this review, we highlight recent advances and challenges in the development and application of LCN, providing examples of their topical, oral, and intravenous drug delivery applications, and discussing translational obstacles to LCN as a NP technology.

Background the study aimed to predict bendamustine pharmacokinetics in paediatric patients by employing physiological-based pharmacokinetic (PBPK) model that considers age-dependent physiological maturity. Methods Using PK-Sim, a paediatric PBPK model was constructed based on a validated PBPK adult model using the recommended paediatric dose at 120 mg/m2 bendamustine intravenous (IV) infusion for 60 minutes and age-dependent mechanistic scaling. Parameter optimisation was done based on model fitting to the observed in vivo population pharmacokinetic (PK) data using the visual predictive check. The final paediatric PBPK model was extrapolated to various paediatric age categories (term newborn, infant, toddler, preschool, school-age, adolescent) for PK estimate and comparisons. The PBPK paediatric model was compared with the adult model, and PK comparisons were made for different age categories with the reference paediatric model. Results The model estimated a bendamustine fraction unbound of 4% in a paediatric patient. Renal clearance, biliary clearance and total hepatic clearance in a typical child were 1.38 mL/min/kg, 0.02 mL/min/kg and 13.76 mL/min/kg respectively. The paediatric model was comparable to the adult model. Compared to a typical child, a term newborn has the highest estimated maximum plasma concentration (Cmax) and systemic exposure (AUC0-24h), which were 1.24-fold respectively. Clearance in term newborn and infant were 1.4-1.5-fold higher than a typical child. Conclusions We developed a bendamustine PBPK model for a paediatric patient with relapsed/refractory Acute Lymphocytic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML). The current model may be useful to estimate systemic exposure in paediatric for various age categories in different settings. More in vivo studies are needed in paediatric patients to challenge the robustness of this model.

Summary Blueberries, a functional food, are rich in bioactive polyphenols and anthocyanins. However, the shelf life is short and requires cold storage. This study provides evidence that edible foxtail millet flour (FMF) efficiently sorbs only blueberry bioactive components (polyphenols and anthocyanins) but not sugars, improves their stability and retains the activity. The concentration of blueberry polyphenols and anthocyanins sorbed to FMF ranged from 6 to 113 and 4 to 41 mg g−1, respectively. The concentration of bioactive components in one serving of blueberries (73 g) is equivalent to those present in 1.2 g of blueberry-enriched foxtail millet flour (BFMF). The blueberry bioactive sorbed onto FMF remained stable for at least 16 weeks at 40 °C. BFMF eluates inhibited α-glucosidase enzyme activity and scavenged the free radicals conferring that blueberry bioactive components in BFMF retained the activity. The sorption process described here provides a practical way of creating low glycemic protein-rich edible flour enriched with plant bioactive compounds without sugars.

Background The transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, Kelch-like ECH-associated protein 1 (KEAP1), are perilous in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation is involved in cytoprotection against many inflammatory disorders. N′-Nicotinoylquinoxaline-2-carbohdyrazide (NQC) was structurally designed by the combination of important pharmacophoric features of bioactive compounds reported in the literature. Methods NQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using Lipopolysaccharide from Escherichia coli (LPSEc) induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using enzyme-linked immune sorbent assay (ELISA). The Nrf2 activity of the compound NQC was determined using ‘Keap1:Nrf2 Inhibitor Screening Assay Kit’. To obtain the insights on NQC’s activity on Nrf2, molecular docking studies were performed using Schrödinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes. Results NQC was found to be non-toxic at the dose of 50 µM on RAW 264.7 cells. NQC showed potent anti-inflammatory effect in an in vitro model of LPSEc stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. NQC dose-dependently down-regulated the pro-inflammatory cytokines [interleukin (IL)-1β (13.27 ± 2.37 μM), IL-6 (10.13 ± 0.58 μM) and tumor necrosis factor (TNF)-α] (14.41 ± 1.83 μM); and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values, 15.23 ± 0.91 µM. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 63.30 ± 1.73, 52.23 ± 0.81, 24.55 ± 1.13 min; microsomal intrinsic clearance values; 1.14 ± 0.31, 1.39 ± 0.87 and 2.96 ± 0.34 µL/min/g liver; respectively. It is observed that rat has comparable metabolic profile with human, thus, rat could be used as an in vivo model for prediction of pharmacokinetics and metabolism profiles of NQC in human. Conclusion NQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.