The aim of this study was to optimize the formulation of meloxicam (MEL)-containing human serum albumin (HSA) nanoparticles for nose-to-brain via a quality by design (QbD) approach. Liquid and dried formulations of nanoparticles containing Tween 80 and without the surfactant were investigated. Various properties, such as the Z-average, zeta potential, encapsulation efficacy (EE), conjugation of MEL and HSA, physical stability, in vitro dissolution, in vitro permeability, and in vivo plasma and brain distribution of MEL were characterized. From a stability point of view, a solid product (Mel-HSA-Tween) is recommended for further development since it met the desired critical parameters (176 ± 0.3 nm Z-average, 0.205 ± 0.01 PdI, −14.1 ± 0.7 mV zeta potential) after 6 months of storage. In vitro examination showed a significantly increased drug dissolution and permeability of MEL-containing nanoparticles, especially in the case of applying Tween 80. The in vivo studies confirmed both the trans-epithelial and axonal transport of nanoparticles, and a significantly higher cerebral concentration of MEL was detected with nose-to-brain delivery, in comparison with intravenous or per os administration. These results indicate intranasal the administration of optimized MEL-containing HSA formulations as a potentially applicable “value-added” product for the treatment of neuroinflammation.

Water is the major component of cells and tissues, and the movement of water across the cell membrane is a fundamental property of life. Until the discovery of the first water channel, aquaporin, it was long assumed that the transport of water was due to simple diffusion through the lipid bilayer membrane that encloses cells. Aquaporin (AQP) molecules were first discovered in the human uterus in 1994, and since then several studies have investigated these channels in the female reproductive system. The expressions of AQPs have been proven in the reproductive system. Their levels are altered during the implantation process, both in the uterus and the fetal cells, and participate in the control of the flow of amniotic fluid. They seem to be very important for the normal placental functions. AQPs are present during parturition, participating in the control of pregnant myometrial contractions and cervical ripening. However, most of the physiological and regulatory roles of AQPs are not clarified in the reproductive tract. Furthermore, no satisfactory knowledge is available about their sensitivities to different drugs. AQP-selective ligands may contribute to the development of new drug candidates and the therapy of several reproductive disorders.

ABC transporters are ubiquitous in the human body and are responsible for the efflux of drugs. They are present in the placenta, intestine, liver and kidney, which are the major organs that can affect the pharmacokinetic and pharmacologic properties of drugs. P-gp and BCRP transporters are the best-characterized transporters in the ABC superfamily, and they have a pivotal role in the barrier tissues due to their efflux mechanism. Moreover, during pregnancy, drug efflux is even more important because of the developing fetus. Recent studies have shown that placental and intestinal ABC transporters have great importance in drug absorption and distribution. Placental and intestinal P-gp and BCRP show gestational-age-dependent expression changes, which determine the drug concentration both in the mother and the fetus during pregnancy. They may have an impact on the efficacy of antibiotic, antiviral, antihistamine, antiemetic and oral antidiabetic therapies. In this review, we would like to provide an overview of the pharmacokinetically relevant expression alterations of placental and intestinal ABC transporters during pregnancy.

Thirteen mammalian aquaporin (AQP) water channels are known, and few of them play a role in the mammalian reproductive system. In our earlier study, the predominance of AQP5 in the late-pregnant rat uterus was proven. Our current aim was to investigate the effect of estrogen- and gestagen-related compounds on the expression of the AQP5 channel in the late-pregnant rat uterus. Furthermore, we examined the effect of hormonally-induced preterm delivery on the expression of AQP5 in the uterus. We treated pregnant Sprague-Dawley rats subcutaneously with 17β-estradiol, clomiphene citrate, tamoxifen citrate, progesterone, levonorgestrel, and medroxyprogesterone acetate. Preterm delivery was induced by subcutaneous mifepristone and intravaginal prostaglandin E2. Reverse-transcriptase PCR and Western blot techniques were used for the detection of the changes in AQP5 mRNA and protein expressions. The amount of AQP5 significantly increased after progesterone and progesterone analogs treatment on 18 and 22 days of pregnancy. The 17β-estradiol and estrogen receptor agonists did not influence the AQP5 mRNA level; however, estradiol induced a significant increase in the AQP5 protein level on the investigated days of gestation. Tamoxifen increased the AQP5 protein expression on day 18, while clomiphene citrate was ineffective. The hormonally-induced preterm birth significantly decreased the AQP5 level similarly to the day of delivery. We proved that AQP5 expression is influenced by both estrogen and progesterone in the late-pregnant rat uterus. The influence of progesterone on AQP5 expression is more predominant as compared with estrogen.

Type 2 diabetes is a chronic disease requiring comprehensive pharmacological and non-pharmacological interventions to slow its progression and prevent or delay its micro- and macrovascular complications. Oxidative stress contributes to the development and progression of type 2 diabetes as well as to the development of its complications through several mechanisms. Therefore, therapeutic targeting of oxidative stress could aid in managing this disease and its complications. In our study, we have collected information on the most frequently used antidiabetic drugs (metformin, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) in the EU and the USA based on their antioxidant effects. Based on our results, we can conclude that the antioxidant effects of the investigated antidiabetics may contribute significantly to the management of the disease and its complications and may open new therapeutic perspectives in their prevention.