Advances in Pharmacological and Pharmaceutical Sciences最新文献

Infections in infants, after childbirth, remain a leading cause of neonatal morbidity and mortality, globally. A soaring percentage of these infections arise from bacterial colonization of the umbilicus. Current therapy for omphalitis includes the topical application of chlorhexidine on the umbilicus. Bacteria such as Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, which are the key causative organisms of omphalitis, are resistant to chlorhexidine. In this study, curcumin-loaded liposomes were prepared using the "thin film hydration" method. Liposomes were characterized by particle size analysis, light microscopy, encapsulation efficiency, and flux. Stable organogels were formed via a high-speed homogenization method and stabilized by an emulsifier mix. They were evaluated for stability over a period by observing for phase separation. Four gels F1 (curcumin-loaded liposomes in chlorhexidine organogel), F2 (curcumin-loaded liposomes in organogel), F3 (chlorhexidine in organogel), and control (plain organogel) were prepared. Physicochemical properties of all gels were evaluated such as organoleptic tests, gel-to-sol transition, rheological studies, pH, skin irritancy, spreadability, accelerated stability, and antibacterial activity studies. Liposomes were spherical with an average size of 7 μm and an encapsulation efficiency of 97%. The in vitro release profile best fits the Higuchi mathematical model implying that curcumin release was by diffusion and dissolution mechanism. In vitro release was also higher at pH 5.5. F1 had the highest spreadability of 63 mm²g^-1 and the lowest viscosity of 184,400 MPas at a shear rate of 10 rotations per minute with a pH of 6.5. Formulation F1 also displayed the highest antibacterial activity against all three bacteria. It can be concluded that the synergistic interaction between curcumin and chlorhexidine may be responsible for the significant antibacterial potency exhibited in formulation F1. Curcumin-loaded liposomes in chlorhexidine organogel (F1) can serve as a prototype for the development of an antibacterial topical formulation having intrinsic activity and enhanced potency to combat omphalitis.

Metformin is the most widely prescribed drug for the treatment of Type 2 diabetes mellitus (T2DM), but its response varies from person to person. This study aims to analyze the complete mutation spectrum of the OCT1 gene in metformin poor responders and to explore the potential pathogenic effects of the identified mutations. Clinical features of 56 Bangladeshi T2DM patients (who showed altered response to metformin) were analyzed, and genomic DNA was extracted from their blood samples. Subsequently, the entire exons (1-11), along with flanking introns of the OCT1 gene were amplified and sequenced. Molecular consequences of the identified mutations on OCT1 protein activity were determined through in silico analyses. In this study, 29 mutations of the OCT1 gene were identified; among which 5 mutations (c.412-86G>T, c.970G>C, c.1386-3088_1386-3083delGAATCA, c.1498+66G>T, and c.1653C>A) were novel. It was found that nsSNPs c.181C>T, c.1022C>T, c.493G>T, c.1207A>G, and c.970G>C (novel) as well as frameshift deletions have potential deleterious effects on OCT1 protein stability and function. Some of these mutations also cause alternative splicing, as per the HSF tool. In addition, alteration of interatomic bonding in the OCT1 protein due to two high-risk mutations (c.181C>T and c.1022C>T) was found from web-based analysis. The mutations, as mentioned earlier, are the most probable causative factor of decreased metformin effectiveness and adverse side effects in T2DM patients who are poor responders. Understanding the OCT1 gene variations of patients can help tailor treatment strategies for optimal metformin response or identify alternative medications.

Recently, seaweed extracts have been found to have potential in skin benefits. This study, therefore, aimed to explore phytochemical analysis, antimicrobial, antioxidant, and wound healing properties of brown seaweed Sargassum plagiophyllym ethanolic extract (SPEE) on human skin keratinocyte HaCaT cells and the possible mechanism involved. Our results indicated that SPEE contained flavonoid, phenolic, and carotenoid as the major active constituents. The HPLC chromatogram revealed C-phycocyanin and fucoidan presented in SPEE. SPEE demonstrated the antioxidant capability and significantly reduced wound space at 24 and 48 h in wound-healing assay. Treatment with SPEE (50 and 100 μg/mL) increased FAK and Src phosphorylation in western blotting. Moreover, SPEE also upregulated Akt and p38 MAPK phosphorylation but not ERK1/2. SPEE increased Rac1 protein expression. Interestingly, hyaluronan synthase (HAS1 and HAS2) as well as collagen type I and elastin were also significantly upregulated when compared with the control upon exposure to SPEE. In conclusion, our data suggested that SPEE promotes cutaneous wound healing by regulating FAK/Src-mediated Akt, p38 MAPK, and Rac1 signaling. These findings suggest the potential use of SPEE for skin wound treatment.

A simple and efficient validated assay for quantifying 21-deoxycortisol (21-DOC), 17-hydroxyprogesterone (17-OHP), cortisol, and cortisone in human plasma has been developed using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Analysis of plasma samples were performed on Atlantis dC18 (3 μm) column using a mobile phase of 20.0 mM ammonium acetate and acetonitrile (50:50, v : v) that was delivered at isocratic flow rate 0.3 mL/minute. After addition of d4-cortisol as an internal standard (IS), plasma samples containing 21-DOC, 17-OHP, cortisol, and cortisone were extracted with mixture of dichloromethane and tert-butylmethyl ether 1:2 (v/v). Analytes were detected and quantified in the positive ion mode of electrospray ionization using multiple reaction monitoring transition set at mass to charge (m/z): 347.17 ⟶ 311.12, 331.17 ⟶ 96.97, 363.11 ⟶ 121.00, 361.18 ⟶ 163.11, and 367.19 ⟶ 121.24 for 21-DOC and 17-OHP, cortisol, cortisone, and cortisol-d4 (IS), respectively. The relationship between concentration and peak area response (analyte/IS) were linear over the range of 0.25-50, 0.5-100, 1-200, and 2-400 ng/mL for 21-DOC, 17-OHP, cortisone, and cortisol, respectively. The mean extraction recovery of the analytes was in the range of 83%-96%. The coefficient of variation within and between days was less than 13.6%, and the bias ranged from -9.2% to 12%. The measured level of cortisol, cortisone, and 17-OHP was in the range of 21.9-110, 4.33-12.71, and 0.37-1.4 ng/mL, respectively. Furthermore, the measured value of cortisone-cortisol ratio was in the range of 0.08-0.21.

Purpose: The current study aimed to improve the oral bioavailability of tenofovir (TNF), an antihuman immunodeficiency viral (HIV) drug, by integrating it into solid lipid nanoparticles (SLNs), an emerging lipid formulation. Method: The suggested SLNs were generated utilizing the microemulsion process, using Compritol 888 ATO. A Box-Behnken experimental design was attempted to analyze the impact of critical quality attributes (CQAs), such as lipid and surfactant content and homogenization duration on response metrics such as particle size (PS) and percentage entrapment. The prepared SLNs were assessed for entrapment efficiency, zeta potential (ZP), PS, polydispersity index, and in vitro drug release. Moreover, ex vivo permeation tests employing goat intestinal sacs, solid-state characterization by DSC and PXRD, surface morphology by SEM, and in vivo pharmacokinetic evaluation using albino Wistar rats were conducted. Results: The research findings demonstrated that a formulation composed of 5.5% lipid and 2% surfactant had a comparatively smaller PS (449.90 ± 4.79 nm), a narrow size distribution (0.304 ± 0.004), and strong stability with an entrapment efficiency of 83.13 ± 6.34% and a negative ZP (-18.10 ± 2.35 mV). According to in vitro drug release experiments, first-order kinetics were followed and 99% of the medication was released over the time course of 24 h. In albino Wistar rats, an in vivo pharmacokinetic analysis of the optimized formulation (F10) showed a 12.4-fold improvement in bioavailability over pure TNF solution. Conclusion: This study suggests the potential of SLNs in overcoming bioavailability issues, particularly low permeability, gut metabolism, and P-gp efflux transport.

Background: Antithrombotic medications, including antiplatelet agents, are standard treatments for patients with hyperlipidemia who have a high risk of developing cardiovascular disease (CVD). The ongoing exploration of new antiplatelet agents with minimal bleeding effects is crucial, including the investigation of potential compounds derived from natural products. This study intended to evaluate the antiplatelet effects of a combined extract of sappan wood (Caesalpinia sappan L.) and red ginger (Zingiber officinale var. Rubrum) in high-fat diet-(HFD)-induced rats. Methods: Eighteen male Wistar rats were grouped into six groups (n = 3): control, negative, positive, and three groups of various combinations of extracts. All groups, excluding the control group, were fed an HFD for 8 weeks. In the eighth week, the control and negative groups were given carboxyl methyl cellulose (CMC) 0.5%, the positive control group was administered aspirin, and the other three groups were administered the combination extract of sappan wood and red ginger at various doses for 2 weeks. Blood samples were collected to assess the levels of hyperlipidemia and platelet hyperactivity markers by enzyme-linked immunosorbent assay (ELISA). The physiological effects of platelet hyperactivity were evaluated using the tail bleeding assay. Results: HFD-induced hypertriglyceridemia and hypercholesterolemia synergistically enhanced platelet hyperactivity after 8 weeks of induction. Interestingly, administration of all doses of the combined extract for 2 weeks significantly decreased the platelet activation markers P-selectin, RANTES, and PCSK9 in a dose-dependent manner compared with the negative control. In addition, the combination of sappan wood and red ginger extract at dose 3 (sappan wood:red ginger: 200:800 mg/200 bw/day) significantly extended the bleeding time of rats (p < 0.05) compared to the negative control. Conclusion: Collectively, our results highlight the antiplatelet effect of a combination of sappan wood and red ginger extract in HFD-fed rats.

Cissus quadrangularis Linn. (C. quadrangularis, Vitaceae) is a plant reported to treat injured tendons, broken bones, asthma, stomach ache, scurvy, and digestive disorders. The present study evaluated the antihyperalgesic effects of ethanolic extract of C. quadrangularis Linn. Vincristine sulfate (100 μg/kg, i.p.) was administered in rats for 10 days with 2 days break to induce painful peripheral neuropathy. Mechanical hyperalgesia and allodynia tests were performed to assess the threshold of painful neuropathy. Calcium levels in the sciatic nerve, oxidant stress markers, and levels of GABA and 5-HT were also determined in the brain and spinal cord after 15 days. Ethanolic extract of C. quadrangularis (180 and 360 mg/kg) and pregabalin (50 mg/kg) were administered for 15 consecutive days. The results revealed that the extract significantly (p < 0.001) inhibited hyperalgesia and allodynia in animals after vincristine administration. The extract decreased total calcium levels in the sciatic nerve, MDA levels while increasing GSH activity, 5-HT level, as well as GABA levels in the brain and spinal cord. The results of this study suggest that the ethanolic extract of C. quadrangularis uses antioxidant capacity, calcium inhibitory action, and neuromodulation of GABA and 5-HT to prevent the development of painful neuropathy after vincristine administration. This demonstrates that C. quadrangularis is a promising molecule for the management of peripheral neuropathic pain induced by anticancer drugs.

This study demonstrated the impact of formic acid (FAc), a common reactive impurity in pharmaceutical excipients, on the stability of mirabegron (MB). The investigation of MB-excipient compatibility tests revealed the formation of a new degradation product, FAc-DP, at 0.2% after 7 days of isothermal stress at 55°C. FAc-DP was synthesized and characterized as N-formyl MB using liquid chromatography-mass spectrometry (LC-MS) and both 1D and 2D nuclear magnetic resonance spectroscopy (NMR).

Background: Good manufacturing practice (GMP) is a part of quality management that maintains product quality and manages it according to the criteria of fitness for use. The heating, ventilation, and air-conditioning (HVAC) system comprises the equipment, technology, and procedure that ensure product quality through maintaining heat, ventilation, and coolness of pharmaceutical manufacturing firms. The aim of the study was to evaluate the GMP compliance of HVAC systems and assess the opportunities and challenges of improving these systems in pharmaceutical manufacturing companies in Ethiopia. Methods: The study was conducted in eight local pharmaceutical manufacturing companies in Ethiopia from April 20 to August 30, 2021, by using a concurrent mixed-method approach to evaluate the implementation of GMP in HVAC systems. The pharmaceutical firms were directly observed by using a structured and standard observational checklist that was adopted from the WHO minimum GMP requirements. In order to understand the challenges and opportunities, face-to-face interviews with key informants using a purposive sampling technique were conducted. Results: The study findings revealed that the local pharmaceutical companies applied for 67.1% of the GMP requirements of the HVAC systems. The GMP implementation status in the basic quality features of HVAC systems of local pharmaceutical companies was 75% on premises, 70.67% in HVAC system design and maintenance practices, 56.25% in product protection, 61.25% in environmental protection, and 75% in cross-contamination prevention. The primary obstacles to implementing GMP in the HVAC systems were a shortage of skilled professionals, HVAC system spare parts, and foreign currency besides poor practice of HVAC system calibration. Conclusion: The study revealed that the local pharmaceutical manufacturing companies did not adhere to GMP standards in HVAC systems.

Since the dawn of civilization, humans have turned to plants as a reliable source of safe and efficient treatment for a wide variety of medical conditions. The medicinal value of Punica granatum has been recognized for some time. Inflammation, diabetes, parasitic infections, cancer, and many other diseases have all been treated with its components. This review provides a comprehensive overview of the current biological data (those from 2018 to 2023 are included in the preclinical studies while articles of clinical studies have no limit due to their scarcity) and explores the potential applications of P. granatum as a novel platform for treating various disease conditions. Electronic searches for scholarly articles were performed using Elsevier, Springer, Google Scholar, Taylor & Francis, PubMed, and Scopus. Research the following terms: "Punica granatum," "chemical composition," "antioxidant," "antibacterial," "anti-diabetic," "anticancer," and other relevant terms. It has been scientifically proven that the fruit peel exhibits antioxidant, anti-inflammatory, antimicrobial, antiparasitic, antidiabetic, hepatoprotective, nerve-recovery, antihypertensive, anti-asthma, wound healing, and anticancer activities. Based on both preclinical and clinical experimentation on P. granatum, there is considerable evidence that supports the use of P. granatum extract as therapeutic agent for different ailments. The review paved the ground to precursor evidence of P. granatum extract benefits with its antioxidant, anti-inflammatory, antimicrobial, and antidiabetic properties. Furthermore, clinical trials stand out as a substrate supporting these effects with the enhancements of ailments including post menstrual, menstrual pain, semen quality, knee joint arthritis, and cardiovascular-related diseases. Nonetheless, more controlled large-scale clinical trials are needed for all the conditions to determine the effectiveness and risk benefit profile of P. granatum extract for these diseases.