Advances in Pharmacological and Pharmaceutical Sciences最新文献

Background: Hypertension and type 2 diabetes (T2D) are the most prevalent noncommunicable diseases in Mexico and worldwide. According to international practice management guidelines, the principal chronic management therapy is daily oral medication.

Aim: We aim to describe the trends of antihypertensive, antidiabetic, and nonsteroidal anti-inflammatory (NSAID) drugs use among the Mexican adult population from 2004-2018.

Methods: We analyzed data from the Health Workers Cohort Study (HWCS) for males and females aged >18 years. We calculated the prevalence of chronic diseases and utilization for every kind of antihypertensive, antidiabetic, and NSAIDs (measured by self-reported utilization) at baseline and two follow-ups (2004, 2010, and 2017). Trends were analyzed using Fisher's exact test.

Results: Hypertension prevalence increased from 19.8 to 30.3%, higher than T2D prevalence from 7.0 to 12.8% through fourteen years of follow-up. Like the self-reported dual therapy, the proportion of patients using beta-blockers and angiotensin II receptor blockers increased. Regarding T2D, the prevalence of metformin utilization increased to 83.9%. The utilization of common NSAIDs, mainly for muscular pain, remained around 13 to 16%.

Conclusions: Our findings showed a changing prevalence of drug utilization for hypertension and T2D between 2004 and 2018 and consistent use of NSAIDs in the adult Mexican population.

The intention of the current work was to develop and optimize the formulation of biodegradable polymeric nanocapsules for lamivudine (LMV) in order to obtain desired physical characteristics so as to have improved liver targetability. Nanocapsules were prepared in this study as aqueous-core nanocapsules (ACNs) with poly(lactide-co-glycolide) using a modified multiple emulsion technique. LMV was taken as a model drug to investigate the potential of ACNs developed in this work in achieving the liver targetability. Three formulations factors were chosen and 3³ factorial design was adopted. The selected formulation factors were optimized statistically so as to have the anticipated characteristics of the ACNs viz. maximum entrapment efficiency, minimum particle size, and less drug release rate constant. The optimized LMV-ACNs were found to have 71.54 ± 1.93% of entrapment efficiency and 288.36 ± 2.53 nm of particle size with zeta potential of -24.7 ± 1.2 mV and 0.095 ± 0.006 h^-1 of release rate constant. This optimized formulation was subjected to surface modification by treating with sodium lauryl sulphate (SLS), which increased the zeta potential to a maximum of -41.6 ± 1.3 mV at a 6 mM concentration of SLS. The results of in vivo pharmacokinetics from blood and liver tissues indicated that hepatic bioavailability of LMV was increased from 13.78 ± 3.48 μg/mL ∗ h for LMV solution to 32.94 ± 5.12 μg/mL ∗ h for the optimized LMV-ACNs and to 54.91 ± 6.68 μg/mL ∗ h for the surface-modified LMV-ACNs.

Monoterpenes are secondary metabolites of plants belonging to the terpenoid class of natural products. They are the most abundant components of essential oils that are generally considered to have various pharmacological properties. These compounds are reported to have antidiabetic effects in recent years. Due to nature's complex biosynthetic machinery, they also exhibit a reasonable degree of structural complexity/diversity for further analysis in structure-activity studies. Therefore, monoterpenes as antidiabetic agents have been investigated by recent in vitro and in vivo studies extensively reported in the scientific literature and claimed by patent documents. The purpose of this survey is to provide a comprehensive and prospective review concerning the potential applications of monoterpenes in the treatment of diabetes. The data for this research were collected through the specialized databases PubMed, Scopus, Web of Science, and ScienceDirect between the years 2014 and 2022, as well as the patent databases EPO, WIPO, and USPTO. The research used 76 articles published in the leading journals in the field. The main effect observed was the antidiabetic activity of monoterpenes. This review showed that monoterpenes can be considered promising agents for prevention and/or treatment of diabetes as well as have a marked pharmaceutical potential for the development of bioproducts for therapeutics applications.

Purpose: This exploratory qualitative study aimed to analyze the experiences of healthcare providers (HCPs) in pharmacovigilance (PV) and ADR reporting in the southern highland zone of Tanzania.

Methods: In 2022, an exploratory qualitative case study using in-depth interviews (IDIs) was conducted to explore the experiences of PV and ADR reporting among HCPs (doctors, nurses, and pharmacists). The study was carried out in a zonal referral hospital and a regional referral hospital of the Tanzanian southern highlands zone. Inductive-deductive thematic analysis was adopted for data analysis.

Results: Participants demonstrated adequate knowledge of PV and its related activities including ADR reporting. Knowing the interactions and wrong medication dosage as sources of ADR, signs, and symptoms, stopping the drug, and treating the symptoms following ADR emerged as subthemes linked with adequate knowledge in identifying and managing ADR. Participants perceived reporting ADR as laborious, posing a subjective burden and that not all ADRs needed to be reported. The latter contributed to limited participation in ADR reporting despite that participants were conversant with both physical and online ADR reporting platforms.

Conclusion: Although HCPs are well informed about PV and ADR reporting including the benefits to public health, their involvement in ADR reporting is low. In addition to the ongoing on-the-job training and regular supportive supervision for HCPs to improve the ADR practice, there is still a need to explore other strategies to be used as motives for HCPs to report ADR regularly.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial regulator of low-density lipoprotein cholesterol (LDL-c) levels, as it binds to and degrades the LDL receptor (LDLR) in the lysosome of hepatocytes. Elevated levels of PCSK9 have been linked to an increased LDL-c plasma levels, thereby increasing the risk of cardiovascular disease (CVD), making it an attractive target for therapeutic interventions. As a way to inhibit PCSK9 action, we searched for naturally derived small molecules which can block the binding of PCSK9 to the LDLR.

Methods: In this study, we carried out in silico studies which consist of virtual screening using an optimized pharmacophore model and molecular docking studies using Pyrx 0.98. Effects of the candidate compounds were evaluated using in vitro PCSK9-LDLR binding assays kit.

Results: Eleven natural compounds that bind to PCSK9 were virtually screened form HerbalDB database, including brazilin. Next, molecular docking studies using Pyrx 0.98 showed that brazilin had the highest binding affinity with PCSK9 at -9.0 (Kcal/mol), which was higher than that of the other ten compounds. Subsequent in vitro PCSK9-LDLR binding assays established that brazilin decreased the binding of PCSK9 to the EGF-A fragment of the LDLR in a dose-dependent manner, with an IC₅₀ value of 2.19 μM.

Conclusion: We have identified brazilin, which is derived from the Caesalpinia sappan herb, which can act as a small molecule inhibitor of PCSK9. Our findings suggest that screening for small molecules that can block the interaction between PCSK9 and the LDLR in silico and in vitro may be a promising approach for developing novel lipid-lowering therapy.

Background: Among all the pharmaceutical dosage forms, tablets are still the most preferred and the most commonly used option because of their advantages. The direct compression method of tablet preparation exempts several steps needed in the granulation method. Therefore, the pursuit of better direct compression tablet excipients is evident in contemporary research endeavors. Pregelatinized Taro Boloso-I starch has comparable flow properties and higher compressibility and compactibility than Starch 1500®. However, there is no evidence in the literature regarding the lubricant sensitivity and dilution potential of pregelatinized Taro Boloso-I starch. This study was aimed at performing the in vitro evaluation of paracetamol tablets prepared using pregelatinized Taro Boloso-I starch as a direct compression excipient using paracetamol as a model drug.

Methods: Taro Boloso-I starch was pregelatinized, and its properties including amylose to amylopectin ratio, densities, flow properties, swelling power, water solubility index, particle morphology, moisture content, and moisture sorption profile were evaluated. Furthermore, the lubricant sensitivity test, dilution potential study, and compatibility test with the paracetamol drug using ATR spectroscopy were performed. The properties of the directly compressed tablets prepared accordingly were evaluated. The majority of evaluations were performed in comparison with Starch 1500®. Results and Discussion. PGTBIS had a significantly lower amount of amylose than Starch 1500®. In the ATR-IR spectra of the mixture of the paracetamol and pregelatinized PGTBIS, all the major absorbance peaks of the drug were maintained indicating the absence of chemical modifications. PGTBIS showed better flow properties than Starch 1500®. The modified starch was shown to withstand magnesium stearate up to 0.5% concentration.

Conclusion: PGTBIS could accommodate higher drug cargo than Starch 1500® with acceptable tablet properties. Accordingly, PGTBIS starch could be taken as a potential direct compression excipient.

Polysaccharide extracts exhibit promise as potential anticancer agents. Among the fungi rich in polysaccharide content, G. applanatum stands out; however, its anticancer activity necessitates further investigation. This study aims to explore the impact of G. applanatum crude polysaccharide (GACP) extract by assessing its effects on cell viability, levels of proinflammatory cytokines such as TNF-α, IFN-γ, IL-2, and IL-12, and levels of proapoptotic markers including caspase-3 and caspase-9, as well as the percentages of necrosis and apoptosis in the HeLa cell line. Employing the HeLa cell line as a research model, four groups were studied: KN (media and DMSO), K+ (doxorubicin 10 μg/mL), P1 (G. applanatum extract 200 μg/mL), and P2 (G. applanatum extract 400 μg/mL). The G. applanatum extract was obtained via boiling distilled water. Anticancer activity was evaluated through the MTT test (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) conducted over three treatment durations (24, 48, and 72 hours). Cytokine levels and caspase-3 and caspase-9 levels were assessed using the ELISA test. Cell apoptosis was determined using the Annexin V-PI biomarker and analyzed through flow cytometry. The MTT test exhibited optimal results at the 48-hour treatment mark. Cytokine level analysis revealed significant reductions in TNF-α, IFN-γ, IL-2, and IL-12 levels (p < 0.005). Concurrently, caspase-3 and caspase-9 levels exhibited substantial increases (p < 0.005). Flow cytometry highlighted the highest percentage of apoptosis in HeLa cells. In conclusion, G. applanatum's polysaccharide extract demonstrates potential as an anticancer and therapeutic agent for cancer treatment.