Omar Awad Alsaidan

The current research work focuses on the extraction and optimization of the hydrogel (AVM) from the seeds of Artemisia vulgaris using Box–Behnken design-response surface methodology (BBD-RSM). The AVM was obtained through a hot water extraction process. The influence of different factors, including pH (U = 4 to 10), temperature (V = 25 to 110 °C), seed/water ratio, i.e., S/W ratio (W = 1/10 to 1/70 w/v), and seed/water contact time, i.e., S/W time (X = 1 to 12 h) on the yield of AVM was evaluated. The p-value for the analysis of variance (ANOVA) was found to be <0.001, indicating that the yield of AVM mainly depended on the abovementioned factors. The highest yield of AVM, i.e., 15.86%, was found at a pH of 7.12, temperature of 80.04 °C, S/W ratio of 1/33.24 w/v, and S/W time of 8.73 h according to Design-Expert Software. The study of the pH-responsive behavior of AVM in tablet form (formulation AVT3) revealed that AVM is a pH-responsive material with significantly high swelling at pH 7.4. However, less swelling was witnessed at pH 1.2. Moreover, AVM was found to be a sustained release material for esomeprazole at pH 7.4 for 12 h. The drug release from AVT3 was according to the super case-II transport mechanism and zero-order kinetics.

Pyrimidines play an important role in modern medical fields. They have a wide spectrum of biological activities such as antimicrobial, anticancer, anti-allergic, anti-leishmanial, antioxidant agents and others. Moreover, in recent years, 3,4-dihydropyrimidin-2(1H)ones have attracted researchers to synthesize them via Biginelli reaction and evaluate their antihypertensive activities as bioisosters of Nifedipine, which is a famous calcium channel blocker. Our new target compounds were prepared through one-pot reaction of thiourea 1, ethyl acetoacetate 2 and/or 1H-indole-2-carbaldehyde, 2-chloroquinoline-3-carbaldehyde, 1,3-diphenyl-1H-pyrazole-4-carbaldehyde, 3a–c in acid medium (HCl) yielding pyrimidines 4a–c, which in turn were hydrolyzed to carboxylic acid derivatives 5a–c which were chlorinated by SOCl2 to give acyl chlorides 6a–c. Finally, the latter were reacted with some selected aromatic amines, namely, aniline, p-toluidine and p-nitroaniline, producing amides 7a–c, 8a–c, and 9a–c. The purity of the prepared compounds was examined via TLC monitoring, and structures were confirmed by different spectroscopic techniques such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The in vivo evaluation of the antihypertensive activity revealed that compounds 4c, 7a, 7c, 8c, 9b and 9c had comparable antihypertensive properties with Nifedipine. On the other hand, the in vitro calcium channel blocking activity was evaluated by IC50 measurement and results revealed that compounds 4c, 7a, 7b, 7c, 8c, 9a, 9b, and 9c had comparable calcium channel blocking activity with the reference Nifedipine. Based on the aforementioned biological results, we selected compounds 8c and 9c to be docked onto Ryanodine and dihydropyridine receptors. Furthermore, we developed a structure–activity relationship. The designed compounds in this study show promising activity profiles in reducing blood pressure and as calcium channel blockers, and could be considered as new potential antihypertensive and/or antianginal agents.

In the last few decades, several natural bioactive agents have been widely utilized in the treatment and prevention of many diseases owing to their unique and versatile therapeutic effects, including antioxidant, anti-inflammatory, anticancer, and neuroprotective action. However, their poor aqueous solubility, poor bioavailability, low GIT stability, extensive metabolism as well as short duration of action are the most shortfalls hampering their biomedical/pharmaceutical applications. Different drug delivery platforms have developed in this regard, and a captivating tool of this has been the fabrication of nanocarriers. In particular, polymeric nanoparticles were reported to offer proficient delivery of various natural bioactive agents with good entrapment potential and stability, an efficiently controlled release, improved bioavailability, and fascinating therapeutic efficacy. In addition, surface decoration and polymer functionalization have opened the door to improving the characteristics of polymeric nanoparticles and alleviating the reported toxicity. Herein, a review of the state of knowledge on polymeric nanoparticles loaded with natural bioactive agents is presented. The review focuses on frequently used polymeric materials and their corresponding methods of fabrication, the needs of such systems for natural bioactive agents, polymeric nanoparticles loaded with natural bioactive agents in the literature, and the potential role of polymer functionalization, hybrid systems, and stimuli-responsive systems in overcoming most of the system drawbacks. This exploration may offer a thorough idea of viewing the polymeric nanoparticles as a potential candidate for the delivery of natural bioactive agents as well as the challenges and the combating tools used to overcome any hurdles.