Application of Biomaterials in the Development of Hydrogel-Forming Microneedles Integrated with a Cyclodextrin Drug Reservoir for Improved Pharmacokinetic Profiles of Telmisartan.

Telmisartan (TEL) is a promising antihypertensive agent among other angiotensin receptor blockers. However, its oral application is limited by its poor water solubility. This study presents the successful utilization of biomaterial-based hydrogel-forming microneedles integrated with a direct compressed tablet reservoir (HFMN-DCT) for the transdermal delivery of telmisartan in the treatment of hypertension. The combination of PVP, PVA, and tartaric acid was used in the HFMN formulation. A range of cross-linking temperatures and times were employed to optimize the characteristics of the HFMN. The HFMN exhibited excellent swelling capacity, mechanical strength, and insertion properties. Additionally, the poorly soluble characteristic of TEL was improved by the inclusion complex formulation with ß-cyclodextrin (ßCD). Phase solubility analysis showed an Ap-type diagram, indicating a higher-order complex between TEL and ßCD, with respect to ßCD. A ratio of TEL:ßCD of 1:4 mM demonstrates the highest solubility enhancement of TEL. The inclusion complex formation was confirmed by FTIR, XRD, DSC, and molecular docking studies. A significantly higher release of TEL (up to 20-fold) from the inclusion complex was observed in the in vitro release study. Subsequently, a DCT reservoir was developed using various concentrations of sodium starch glycolate. Essentially, both the HFMN and DCT reservoir exhibit hemocompatibility and did not induce any skin irritation. The optimized combination of the HFMN-DCT reservoir showed an ex vivo permeation profile of 83.275 ± 2.405%. Notably, the proposed system showed superior pharmacokinetic profiles in the in vivo investigation using male Wistar rats. Overall, this study highlights the potential of HFMN-DCT reservoir systems as a versatile platform for transdermal drug delivery applications.

microRNA hsa-miR-425-5p and hsa-miR-4523 expressions as biomarkers of active pulmonary tuberculosis, latent tuberculosis infection, and lymph node tuberculosis.

Background: Studies on miRNA highlight its significance as an immunomarker for several diseases, including tuberculosis. This study aimed to determine the difference between miR-425-5p and miR-4523 expressions in patients with active pulmonary TB (PTB), latent TB infection (LTBI), and lymph node TB (LNTB), whose diagnosis remains challenging. Methods: This case-control study was performed on blood samples obtained from 23 patients with PTB, 21 with LTBI, 21 with LNTB, and 25 healthy controls (HC). miRNA hsa-miR-425-5p and hsa-miR-4523 expression levels were measured by RT-qPCR. Statistical analyses were performed using SPSS version 25.0. Results: RT-qPCR showed that hsa-mir-425-5p and hsa-mir-4523 expression levels were significantly different among the four groups (PTB, LTBI, LNTB, and HCs). The hsa-mir-425-5p miRNA expression level in LNTB was higher than that in LTBI (p = 0.003). Meanwhile, the hsa-mir-4523 miRNA expression was downregulated in PTB and LNTB than in LTBI (p < 0.0001 and p = 0.015, respectively). The ROC analysis of a single sample showed that only mir-4523 could discriminate LTBI and HCs, with an AUC of 0.829 (p < 0.001). The ROC curve of each miRNA was further analyzed after logistic regression by adjusting for sex and age. The combination of both miRNAs was also analyzed. The model that analyzed the combination of both miRNAs after adjusting for age had the best performance in differentiating LNTB from LTBI, with an AUC of 0.97 (p < 0.001). Conclusion: miRNA hsa-mir-425-5p was upregulated and miRNA hsa-mir-4523 was downregulated in PTB and LNTB than in LTBI.

Docking Studies and Molecular Dynamics Simulations of Potential Inhibitors from the Brown Seaweed Sargassum polycystum (Phaeophyceae) against PLpro of SARS-CoV-2.

The COVID-19 disease is a major problem affecting human health all over the world. Consequently, researchers have been trying to find solutions to treat this pandemic-scale disease. Even if there are vaccines and approved drugs that could decrease the spread of this pandemic, multidisciplinary approaches are still needed to identify new small molecules as alternatives to combat COVID-19, especially those from nature. In this study, we employed computational approaches by screening 17 natural compounds from the tropical brown seaweed Sargassum polycystum known to have anti-viral properties that benefit human health. This study assessed some seaweed natural products that are bound to the PLpro of SARS-CoV-2. By employing pharmacophore and molecular docking, these natural compounds from S. polycystum showed remarkable scores for protein targets with competitive scores compared to X-ray crystallography ligands and well-known antiviral compounds. This study provides insightful information for advanced study and further in vitro examination and clinical investigation for drug development prospects of abundant yet underexploited tropical seaweeds.

Potential bioactive compounds as SARS-CoV-2 inhibitors from extracts of the marine red alga Halymenia durvillei (Rhodophyta) - A computational study.

The respiratory infection COVID-19 caused by the virus SARS CoV-2 has continued to be a major health problem worldwide and has caused more than a million mortalities. Even if the development of COVID-19 vaccines has shown much progress, efforts to find novel, natural anti-viral drugs should be pursued. Halymenia durvillei is a marine red alga widely distributed around Southeast Asia. This study aimed to develop new anti SARS CoV-2 compounds from ethanolic and ethyl acetate extracts of H. durvillei via a computational approach, focusing onthe inhibitory action against the main protease (3CL-Mpro). In this study, 37 compounds were extracted and identified by GC-MS analysis. The potentials of compounds 1-2 tetradecandiol and E,E,Z-1,3,12-nonadecatriene-5,14-diol were identified for therapeutic purposes based on our pharmacophore study, while cholest-5-En-3-Ol (3.Beta.)- had a high fitness score in molecular docking studies both in monomer and dimer state compared to the N3 inhibitor and remdesivir affinity scores. As these compounds show competitive affinity scores against the 3CL-Mpro, these natural compounds may be effective for the treatment of COVID-19 infection. The ADME and pharmacokinetic studies should also be employed to assess the ability of the natural compounds as oral drugs. These promising results have shown the potentials of H. durvillei as an alternative drug in addressing COVID-19 infection. Accordingly, further studies should explore the effectiveness of these active compounds.