Benzaldehyde, A New Absorption Promoter, Accelerating Absorption on Low Bioavailability Drugs Through Membrane Permeability

Styrax, one of the most famous folk medicines, is a necessary medicine in formulas to help other drugs reach the focal zone and maximize the effectiveness, the mechanism that promotes absorption is not clear yet. This study was carried out to investigate the absorption-promoting effects and the mechanism of benzaldehyde, a key active compound of styrax, on the diffusion rates of drugs with different oral bioavailability. Caco-2 transport experiments were used to investigate the transport rate. Molecular Dynamics Simulation analysis and fluorescence-anisotropy measurements were used to explore the underlying mechanism of absorption-promoting. Validation test in vivo was carried out to reveal the absorption-promoting effects of benzaldehyde on high hydrophilicity drugs. Our data indicated that benzaldehyde(50 μM) elevated the cumulative quantity of passively diffusion drugs with high hydrophilicity such as acyclovir and hydrochlorothiazide. MD and membrane fluidity data explained that benzaldehyde can loosen the structure of the lipid bilayer. The validation tests showed that benzaldehyde (140 mg/kg) remarkably increased the Cmax and AUC0-6 of acyclovir and hydrochlorothiazide in vivo. These present studies suggested that benzaldehyde can promote the absorption of drugs with a lower oral bioavailability through disturbing the integrity of lipid bilayer enhanced membrane permeability.

The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs

The polyamidoamine (PAMAM) dendrimer is a highly efficient absorption promoter. In the present study, we studied the absorption-enhancing effects and the mechanism of PAMAM dendrimers with generation 0 to generation 3 (G0–G3) and concentrations (0.1–1.0%) on the pulmonary absorption of macromolecules. The absorption-enhancing mechanisms were elucidated by microarray, western blotting analysis, and PCR. Fluorescein isothiocyanate-labeled dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption-enhancing effects of PAMAM dendrimers on the pulmonary absorption of FDs were in a generation- and concentration-dependent manner. The G3 PAMAM dendrimer with high effectiveness was considered to the best absorption enhancer for improving the pulmonary absorption of FDs. G3 PAMAM dendrimers at three different concentrations were non-toxic to Calu-3 cells. Based on the consideration between efficacy and cost, the 0.1% G3 PAMAM dendrimer was selected for subsequent studies. The results showed that treatment with a 0.1% G3 PAMAM dendrimer could increase the secretion of organic cation transporters (OCTs), OCT1, OCT2, and OCT3, which might be related to the absorption-enhancing mechanisms of the pulmonary absorption of FDs. These findings suggested that PAMAM dendrimers might be potentially safe absorption enhancers for improving absorption of FDs by increasing the secretion of OCT1, OCT2, and OCT3.

Formulation of Iron Fortified Masala Powders and Assessment of its Nutritional and Sensory Qualities

Tamarind (Tamarindus indica), an acidulant spice, is a rich source of tartaric acid, an iron absorption promoter. Hence, in this context, the study aimed at formulating iron fortified tamarind based spice mixes used for South Indian dishes (Puliyogare, Rasam, Bisibele-bhat and Sambar) and analyze their nutritional and sensory quality. Masala powders were formulated using tamarind powder, pulses, salts and spices and fortified with either ferrous sulfate or ferrous fumarate to yield 2.0 mg iron/100g or ml of serving. Non-fortified products served as controls. Products were analyzed for nutrients, anti-nutrients and bio accessible iron using standard methods and evaluated for sensory attributes by 48-60 members. The range of constituents in dry tamarind and control masala powder per 100g respectively were as follows:- protein, 3.68 and 5.30-8.70%; fat, 0.36 and 3.26-6.80%; iron,18.27 and 6.2-11.5mg; calcium, 97.4 and 120.6-198.9mg; oxalates, 120.1 and 156.5- 366.2mg; phytates, 728.4 and 122.2- 176.7mg and tannins, 1240 and 204-233.2mg. Iron content in fortified products ranged from 28.3-47.2mg/100g respectively. More than 70% of iron was bioaccessible in iron fortified products, in comparison to 30-37% in control products. All the products were highly acceptable by panel members for all sensory attributes.

Peri- and Postnatal Developmental Toxicity of Salcaprozate Sodium (SNAC) in Sprague-Dawley Rats

Salcaprozate sodium (SNAC) (sodium 8-((2-hydroxybenzoyl) amino) octanoate, CAS RN 203787-91-1) is classified as an oral absorption promoter and may be a useful means for improving the absorption of certain nutrients and pharmaceutical agents. Presented herein is a subset of data from a larger study evaluating the potential effects of SNAC on the gestation, parturition, lactation, maternal behavior, and offspring development of rats. Pregnant Crl:CD BR VAF/Plus female rats (F0; n = 25) received SNAC at 1000 mg/kg/d orally (gavage) from implantation through lactation and weaning. F1 pups were exposed in utero and potentially through maternal milk; observations continued through sexual maturity. The study concluded with Caesarean sectioning of F1 dams for litter observations and fetal evaluations. No deaths, abortions, premature deliveries, or gross lesions occurred in (F0) dams. Excess salivation, red perivaginal substance, and slight reductions in body weights, body weight gains, and/or feed intake were noted in late gestation/early lactation. SNAC was associated with a prolonged gestation period, leading to a greater number of dams with stillborn pups, higher number of stillborn pups, and reduced live litter size. Offspring body weights/gains, feed consumption, age of sexual maturation, mating, fertility, behavioral parameters, and organ weights at necropsy were unaffected by SNAC. No gross external changes were observed in F1 or F2 pups. In summary, SNAC administered orally at 1000 mg/kg/d to pregnant rats from gestation to weaning resulted in a slight decrease in maternal body weights (−3.8%) and prolonged gestation, along with an increase in stillbirths, but had no effects on growth and development in surviving offspring.