Saudi Pharmaceutical Journal最新文献

The concept of the vitamin D response index was developed based on vitamin D intervention studies conducted with Finnish cohorts. In this study, we challenged the concept by performing a single vitamin D₃ bolus (80,000 IU) intervention with a cohort of 100 native Saudis. The change of serum levels of the proinflammatory cytokines interleukin 6, interleukin 8 and tumor necrosis factor measured directly before intervention in comparison to samples taken one and thirty days after vitamin D₃ supplementation were used as biomarkers for distinguishing low, mid and high responders. Interestingly, we identified 39 % of the study participants as low responders. In contrast, when we used in a subset of 37 study participants whole blood expression changes of seven well-known vitamin D target genes one and thirty days after supplementation as alternative biomarkers, only 9 persons (24 %) were identified as low responders. In conclusion, in Saudi Arabia the rate of low vitamin D responders is equal or even higher than that in Finland. Therefore, similar to Nordic countries also in Saudi Arabia appropriate vitamin D₃ supplementation is essential, in order to fulfill the needs of low responders.

This study aimed to investigate the impact of storage conditions on the dissolution performance of commercial metronidazole (MTZ) tablets available in Saudi Arabia; these were coded as the reference and Test A, Test B, and Test C products. Moreover, the hardness and the disintegration time were measured. The UV spectrophotometrically analytical technique was utilized to quantify MTZ. All the control tablets, which were tested upon receipt, met the USP requirement as not less than 85 % of the labeled amount of MTZ was dissolved in 60 min. The MTZ reference released 91.79 % ± 1.23 after 60 min, while the products A, B, and C released 87.96 % ± 2.60, 93.26 % ± 2.01, and 88.61 % ± 2.04, respectively. The different dissolution parameters calculated for all the control tablets showed that the MTZ products A and B had optimal dissolution performances and were considered similar to the reference product. The product C showed a significantly reduced dissolution performance and was considered different from the reference. The in vitro dissolution of the MTZ tablets stored at 40oC ± 2 oC/75 % RH ± 5 % for 6 months indicated that the tablets maintained compliance with the USP requirement. The MTZ reference released 89.36 % ± 3.64 after 60 min, while the products A, B, and C released 95.79 % ± 3.91, 88.52 % ± 2.52, and 87.79 % ± 5.04, respectively. However, a slight reduction in the percentage released after 30 min (% DE30) and a slight increase in the mean dissolution time (MDT) were observed during the first 3 months of storage under stressed conditions. These changes were more obvious after 6 months of storage under the same conditions. Furthermore, in vitro dissolution of the product C stored at 40oC ± 2 oC/75 % RH ± 5 % for 3 months with further protection against high humidity revealed an improvement in the dissolution parameters due to the similar protective effects exerted by the two packaging forms. Furthermore, the study shows that storage conditions such as humidity and temperature affect in vitro dissolution of MTZ marketed tablets which may have an impact on efficiency and patient safety.

In the past two decades, the world has witnessed devastating pandemics affecting the global healthcare infrastructure and disrupting society and the economy worldwide. Among all pathogens, viruses play a critical role that is associated with outbreaks due to their wide range of species, involvement of animal hosts, easily transmitted to humans, and increased rates of infectivity. Viral disease outbreaks threaten public health globally due to the challenges associated with controlling and eradicating them. Implementing effective viral disease control programs starts with ongoing surveillance data collection and analyses to detect infectious disease trends and patterns, which is critical for maintaining public health. Viral disease control strategies include improved hygiene and sanitation facilities, eliminating arthropod vectors, vaccinations, and quarantine. The Saudi Ministry of Health (MOH) and the Public Health Authority (also known as Weqayah) in Saudi Arabia are responsible for public health surveillance to control and prevent infectious diseases. The notifiable viral diseases based on the Saudi MOH include hepatitis diseases, viral hemorrhagic fevers, respiratory viral diseases, exanthematous viral diseases, neurological viral diseases, and conjunctivitis. Monitoring trends and detecting changes in these viral diseases is essential to provide proper interventions, evaluate the established prevention programs, and develop better prevention strategies. Therefore, this review aims to highlight the epidemiological updates of the recently reported viral infections in Saudi Arabia and to provide insights into the recent clinical treatment and prevention strategies.

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

Objective

Skin cancer refers to the pathological condition characterized by the proliferation of atypical skin cells in an uncontrolled manner. Plant-based products such as bixin although show promising anticancer properties, but maintaining their stability in a formulation is a difficult task. The objective of the research is to formulate a silver nanoparticle gel preparation of bixin and evaluate its anticancer properties.

Methods

The extract from Bixa orellana seed was prepared by hot extraction technique to isolate the active ingredient, bixin. A green synthesis approach was utilized for preparing the silver nanoparticle gel of bixin (BOAgNPs). Characterization of silver nanoparticles was done using FTIR, scanning electron microscopy, compatibility study, homogeneity testing, pH evaluation, and drug content determination. The in-vitro anticancer activity was performed using cell lines (B16F10) and in-vivo by chemical carcinogen (7,12-dimethylbenz (a) anthracene) in mice.

Results

The BOAgNPs-loaded topical gel was found to be homogeneous (clear orange color) and pH-compatible (pH ≈ 6.66) with the skin. The characterization studies indicated the presence of all functional groups in the formulation. An optimized batch of bixin-nano gel showed about 60% inhibitory effects on B16F10 cell lines (in-vitro activity) when equated with a reference drug, 5-fluorouracil. The in-vivo anticancer study suggested suppression of tumorigenesis and promotion of the healing process with bixin-nano gel application on the skin.

Conclusion

The results suggested the promising anticancer property of bixin when formulated in silver nanoparticle gel. The preparation of silver particles nano gel with bixin might provide an effective alternative option for treating skin cancers, provided more research complements the findings of the present study.

Biodegradable and biocompatible biomaterials have several important applications in drug delivery. The biomaterial family known as poly(ester amide)s (PEAs) has garnered considerable interest because it exhibits the benefits of both polyester and polyamide, as well as production from readily available raw ingredients and sophisticated synthesis techniques. Specifically, α-amino acid-based PEAs (AA-PEAs) are promising carriers because of their structural flexibility, biocompatibility, and biodegradability. Herein, we summarize the latest applications of PEAs in drug delivery systems, including antitumor, gene therapy, and protein drugs, and discuss the prospects of drug delivery based on PEAs, which provides a reference for designing safe and efficient drug delivery carriers.

Aging is a natural process that occurs in all living organisms. Particularly, the skin embodies aging since it serves as a barrier between the body and its surroundings. Previously, we reported the wound healing effect of Launaea procumbens and identified compounds therein. The study aims to explore the skin anti-aging properties of the plant extract. To that effect, the antioxidant potential of L. procumbens methanolic extract (LPM) was assessed using two complementary DPPH and FRAP assays. The enzyme inhibitory effect of the extract on collagenase, elastase, hyaluronidase, and tyrosinase was evaluated to assess the direct skin anti-aging effects. Similarly, the anti-inflammatory activity was evaluated to explore the indirect anti-aging effects via the assessment of extract inhibitory effects on cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). In addition, ADMET and molecular docking studies were performed to explore the interaction mechanisms of identified compounds in LPM with target enzymes. LPM demonstrated significant antioxidant activity in DPPH (IC₅₀ = 29.08 µg/mL) and FRAP (1214.67 µM FeSO4/g extract) assays. Plant extract showed significant inhibition of collagenase, elastase, hyaluronidase, and tyrosinase (IC₅₀ = 52.68, 43.76, 31.031, and 37.13 µg/mL, respectively). The extract demonstrated significant COX-2 and 5-LOX inhibition capacity with IC₅₀ values of 8.635 and 10.851 µg/mL, respectively. The molecular docking study revealed the high potential of the identified compounds to bind to the active sites of enzymes crucially involved in the skin aging process. ADMET analysis of the compounds revealed their good absorption, distribution, and metabolism profiles, and they were found to be safe as well. Study findings suggest L. procumbens as a promising source for the development of natural skin anti-aging and antioxidant compounds. This, in turn, may facilitate its incorporation into cosmetic formulations after further investigation.

Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-β) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-β mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.

This study aimed to provide an understanding of the influence of eugenol on CYP1A2, 2C9, 2D6, and 3A4 in human liver microsomes (HLM). Specific substrate for CYP1A2, 2C9, 2D6, and 3A4 were incubated in HLM with or without eugenol. The formation of their respective metabolites was assessed with HPLC analytical methods. Eugenol at 1, 10 and 100 µM levels inhibited the activity of CYP1A2 and CYP2C9 by 23.38 %, 23.57 %, 39.80 % and 62.82 %, 63.27 %, 67.70 % respectively. While, CYP2D6 and CYP3A4 activity was decreased by 40.70 %, 45.88 %, 62.68 % and 37.41 %, 42.58 % and 67.86 % at 1, 10 and 100 µM eugenol level respectively. The IC₅₀ value of eugenol for CYP2D6 and CYP3A4 was calculated as 11.09 ± 3.49 µM and 13.48 ± 3.86 µM respectively. Potential herb-drug interactions was noted when eugenol is administered simultaneously with medications metabolized by these enzymes, most notably CYP2C9, CYP2D6 and CYP3A4.

Colorectal cancer is one of the major causes of global cancer, with chemotherapy and radiation therapy being effective but limited due to low specificity. Regorafenib, a multikinase inhibitor, provides hope to patients with metastatic colorectal cancer and was approved by the FDA in 2012. However, due to resistance issues and adverse events, its efficacy is compromised, necessitating further refinement. Meanwhile, curcumin, a compound of turmeric, exhibits anticancer effects through antioxidant and anti-inflammatory actions, induction of the apoptosis, arrest of cell cycle, inhibition of angiogenesis, and modulation of signaling pathways. Unfortunately, its clinical utility is limited by its poor bioavailability, pointing towards innovative drug delivery strategies for enhanced efficacy in colorectal cancer treatment.

Hyaluronic acid (HA)-decorated liposomes (LIPO) have been developed to target colorectal cells through an overexpressed CD44 receptor, increasing antitumor and antimetastasis efficacy. This study investigates the possibility of loading curcumin (CUR) or regorafenib (REGO) into a liposomal formulation for passive and HA-actively targeted treatment, evaluating its critical quality attributes (CQA) (size, zeta potential, polydispersity index) and cytotoxic activity in the HT29 colorectal cancer cell line. The average particle size of the plain liposomes and those decorated with HA was 144.00 ± 0.78 nm and 140.77 ± 1.64 nm, respectively. In contrast, curcumin-loaded plain liposomes and HA-decorated liposomes had 140 ± 2.46 nm and 164.53 ± 15.13 nm, respectively. The prepared liposomes had a spherical shape with a narrow size distribution and an acceptable zeta potential of less than −30 mV. The encapsulation efficiency was 99.2 % ± 0.3 and 99.9 ± 0.2 % for HA-decorated and bare regorafenib loaded. The % EE was 98.9 ± 0.2 % and 97.5 ± 0.2 % for bare liposomal nanoparticles loaded with curcumin and coated with curcumin. The IC₅₀ of free REGO, CUR, REGO-LIPO, CUR-LIPO, REGO-LIPO-HA and CUR-LIPO-HA were 20.17 ± 0.78, 64.4 ± 0.33, 224.8 ± 0.06, 49.66 ± 0.22, 73.66 ± 0.6, and 27.86 ± 0.49 µM, respectively. The MTT assay in HT29 cells showed significant cytotoxic activity of the HA-decorated liposomal formulation compared to the base uncoated formulation, indicating that hyaluronic acid-targeted liposomes loaded with regorafenib or curcumin could be a promising targeted formulation against colorectal cancer cells.