Avanafil (AVN) is a new selective phosphodiesterase-5 (PDE-5) inhibitor, which is used as an oral treatment of
erectile dysfunction. Coadministration of avanafil (AVN) with some antihypertensive drugs especially in elderly
patients is a very common case. Nimodipine (NIM) is one of these hypotensive drugs that are commonly
coadministered. Synergistic hypotension effect as a result of AVN and NIM coadministration is expected;
therefore, it is mandatory to study the possible pharmacokinetic interaction between them. The main aim of the
current work is to develop a simple, sensitive, and selective electrochemical method for simultaneous determination of AVN and NIM in human serum samples. Nickel oxide nanoparticles/poly(sulfanilamide) film was
used as a new electrochemical modifier, which is electrodeposited on the surface of pencil graphite electrode
(PGE) to improve its electrochemical properties. The best resolution between the two studied drugs was achieved
by using Britton-Robinson buffer (BRB) at pH 3.0 producing two peaks at 1.45 V and 0.80 V for AVN and NIM,
respectively. Furthermore, cyclic voltammetry was utilized for the first time to study the oxidation behavior of
AVN and NIM and a plausible oxidation mechanism was suggested for both of them. The proposed square wave
voltammetric method was successfully applied for trace quantification of AVN and NIM in real human serum
samples with detection and quantitation limits of 0.037 and 0.10 μmol L- 1 for AVN and 0.32 and 0.98 μmol L- 1
for NIM, respectively. Moreover, the suggested approach was effectively implemented to investigate the possible
pharmacokinetic interaction between AVN and NIM in serum samples of heathy human male volunteers. It was
found from the pharmacokinetic parameters calculated for AVN when administered alone or in presence of NIM
that there is a significant increase of serum concentration of AVN, when it is coadminstered with NIM, which
stresses the importance of dose adjustment of AVN when coadministered with NIM.

Diatoms are unicellular photosynthetic algae enclosed in 3-dimensional (3D) nano patterned silica cell walls called frustules. They are made of intricate porous biosilica that feature unique properties including high specific surface area, biocompatibility, tailorable surface chemistry, thermal stability and high mechanical and chemical resistance. Additionally, the facile cultivation of diatoms in artificial environment, and the abundant availability of diatom frustules as fossilized mineral (diatomite) from mining industry confirm the benefits of using diatoms as an alternative to synthetic porous silica for a broad range of applications. These attributes make them a remarkable candidate for a variety of biomedical applications including drug delivery. In this chapter, the potential use of diatoms, as micro- and nano frustules (i.e., silica) or reduced to silicon replicas, for biomedical applications with emphasis on their use as drug carriers is described. The selected aspects on the preparation of diatom frustules, in addition to surface chemical functionalization, drug loading, their cellular uptake as well as capability to transport therapeutic molecules inside cells are presented

Paediatric titanium (Ti) implants are used for the short-term fixation of fractures, after which they are removed. However, bone overgrowth on the implant surface can complicate their removal. The current Ti implants research focuses on improving their osseointegration and antibacterial properties for long-term use while overlooking the requirements of temporary implants. This paper presents the engineering of additively manufactured Ti implants with antibacterial properties and prevention of bone cell overgrowth. 3D-printed implants were fabricated followed by electrochemical anodization to generate vertically aligned titania nanotubes (TNTs) on the surface with specific diameters (∼100 nm) to reduce cell attachment and proliferation. To achieve enhanced antibacterial performance, TNTs were coated with gallium nitrate as antibacterial agent. The physicochemical characteristics of these implants assessed by the attachment, growth and viability of osteoblastic MG-63 cells showed significantly reduced cell attachment and proliferation, confirming the ability of TNTs surface to avoid cell overgrowth. Gallium coated TNTs showed strong antibacterial activity against S. aureus and P. aeruginosa with reduced bacterial attachment and high rates of bacterial death. Thus a new approach for the engineering of temporary Ti implants with enhanced bactericidal properties with reduced bone cell attachment is demonstrated as a new strategy toward a new generation of short-term implants in paediatrics.

p75ECD-Fc is a novel antagonist of toxic amyloid beta protein and other neurodegenerative factors with potential for the treatment of Alzheimer’s disease (AD). Preclinical studies showed that it can alleviate the AD pathologies in animal models of dementia. In a previous paper, we used non-compartmental pharmacokinetic analysis to obtain preliminary pharmacokinetic data for p75ECD-Fc in Sprague Dawley (SD) rats. We also studied the tissue distribution in terms of drug metabolism that helped us to understand possible mechanisms of action. Here, we aim to develop population pharmacokinetic models that can describe the pharmacokinetics of p75ECD-Fc in serum and tissues.

Methods

p75ECD-Fc was delivered to SD rats via two routes (intravenous and subcutaneous) at a single dose of 3 mg/kg (n = 15). Blood (n = 12) and tissue samples (n = 10–15) were then separated at different time points for a total duration of 42 days post dosage. The concentration of p75ECD-Fc in serum and tissues was measured using an enzyme-linked immunosorbent assay.

Results

Data were best fitted to a 2-compartment model with linear elimination kinetics. The population parameter estimates for clearance, and volume of central and peripheral compartments were 0.000176 L/h, 0.0145 L and 0.0263 L, respectively. The presence of anti-drug antibodies was added to the final model as a covariate on clearance. The subcutaneous bioavailability was estimated to be 53.5% with a first-order absorption rate constant of 0.00745 1/h. By modeling of individual tissue concentrations, p75ECD-Fc was found to exhibit modest tissue distribution with estimated tissue/plasma partition coefficients (R) ranging from 0.004 to 0.2.

Conclusion

This is the first report of a pharmacokinetic model for p75ECD-Fc and these results may facilitate the ongoing development of p75ECD-Fc and translation to clinical studies.

Oxidative stress is a key factor in the pathogenesis of several neurodegenerative disorders and is involved in the accumulation of amyloid beta plaques and Tau inclusions. Edaravone (EDR) is a free radical scavenger that is approved for motor neuron disease and acute ischemic stroke. EDR alleviates pathologies and cognitive impairment of AD via targeting multiple key pathways in transgenic mice. Herein, we aimed to study the effect of EDR on Tau pathology in P301L mice; an animal model of frontotemporal dementia (FTD), at two age time points representing the early and late stages of the disease. A novel EDR formulation was utilized in the study and the drug was delivered orally in drinking water for 3 months. Then, behavioral tests were conducted followed by animal sacrifice and brain dissection. Treatment with EDR improved the reference memory and accuracy in the probe trial as evaluated in Morris water maze, as well as novel object recognition and significantly alleviated motor deficits in these mice. EDR also reduced the levels of 4-hydroxy-2-nonenal and 3-nitrotyrosine adducts. In addition, immunohistochemistry showed that EDR reduced tau phosphorylation and neuroinflammation and partially rescued neurons against oxidative neurotoxicity. Moreover, EDR attenuated downstream pathologies involved in Tau hyperphosphorylation. These results suggest that EDR may be a potential therapeutic agent for the treatment of FTD.

p75ECD-Fc is a recombinant human protein that has recently been developed as a novel therapy for Alzheimer’s disease. Current studies showed that it is able to alleviate Alzheimer’s disease pathologies in animal models of dementia. Thus, knowledge about the pharmacokinetic behavior and tissue distribution of this novel protein is crucial in order to better understand its pharmacodynamics and more importantly for its clinical development.