Tropical Journal of Pharmaceutical Research

Characterization of in vitro spray-dried self-nanoemulsifying drug delivery systems for oral delivery of Bundung extract

Noval — 2025-05-30

drying method and to enhance solubility and bioavailability of Bundung (Actinoscirpus grossus) plant extract as an antioxidant. Methods: The procedure was delineated into six sequential steps. Bundung extract was obtained from the plant by maceration in ethanol for 3 days. Subsequently, five formulations of L-SNEDDS with varying concentrations of oleic acid were prepared, followed by the characterization of liquid SNEDDS (L-SNEDDS). This characterization encompassed transmittance, emulsification time and determination of droplet size, polydispersity index and zeta potential (ZP). The third step involved preparation of S-SNEDDS through the use of a spray drying technique. The fourth step entailed the characterization of S-SNEDDS, which included visual observation, resistance to dilution, globule size measurement, and Differential Scanning Calorimetry. The fifth step involved an in vitro drug release test. The sixth step involved an antioxidant activity test using DPPH and FRAP. Results: Formulation 1 of L-SNEDDS showed 99.3 % transmittance, had the smallest droplet size and best particle distribution, while formulation 2 emulsified fastest in the gastrointestinal tract. Furthermore, formulations 1, 2, 3 and 5 had optimum ZP values. In converting liquid SNEDDS to solid SNEDDS, formulation 3 had a 100 % yield, while formulation 1 had the smallest globule size and the highest antioxidant activity. Conclusion: Formulation 1 of Bundung extract, with 5 % Oleic Acid concentration, is the most optimized as it meets the characterization requirements of L-SNEDDS and S-SNEDDS, passes the in vitro drug release test and has the highest antioxidant activity.

Nanostructured lipid carriers loaded with capecitabine modulate apoptosis via IL-6 signaling: A novel approach to targeted cancer therapy

Mohammad Alam — 2025-05-30

Purpose: To examine the impact of capecitabine-loaded nanostructured lipid carriers (NLC) on cancer cell death mechanisms and apoptosis through interleukin-6 (IL-6) signaling system. Method: In a triplicate MTT assay, cell viability was assessed using 100 μg/mL capecitabine-loaded nanostructured lipid carrier (NLC) formulation. Apoptotic DNA degradation was determined by DNA fragmentation analysis. The molecular processes behind cellular responses were clarified by gene expression profiling of IL-6 pathway components. The formulations were characterized using zeta potential, particle size, and polydispersity index (PDI). Furthermore, morphological analysis, MTT testing, DNA fragmentation assay, and qRT-PCR were used to examine gene expression of interleukin cytokines IL-6, IL-6R, gp130, Bcl-2, Bax, NF-kB, and JAK-STAT. Results: Microscopic examination of cell lines revealed morphological alterations suggestive of cell death and apoptosis. Results from MTT assay showed that nano-formulation had a much lower IC50 (8 μg/mL) compared to pure drug (48 μg/mL). There were statistically significant (p < 0.05) differences between nano formulation and pure drug in each treatment concentration. Expression of inflammatory and apoptotic genes was significantly lower in pure and Nano-Cap treated cell lines compared to control (p < 0.05). However, treatment with Nano-Cap significantly reduced expression of inflammatory and apoptotic markers compared to pure drug (p < 0.05). Furthermore, level of Bax was significantly increased (p < 0.001) in Nano-Cap-treated cell lines compared to pure drug and control Conclusion: Capecitabine-loaded nanostructured lipid carriers (NLC) are more effective than pure drug in treating colon cancer. The results may contribute to developing more effective, targeted cancer therapies and personalized treatment strategies by elucidating the interplay between nanoparticle drug delivery, chemotherapy agents, and intracellular signaling pathways.

Effect of chitosan-silver nanoparticle composite-treated water on selected biochemical parameters of rats

Raliat Aladodo — 2025-05-30

Purpose: To investigate the impact of chitosan-silver nanoparticles (chitosan-AgNP) composite-treated water on some biochemical parameters in the albino rats.

Methods: Water samples were pretreated with chitosan-coated silver nanoparticles (chitosan-AgNPs) prior to oral administration in a rodent model. Following a 28-day experimental period, serum biochemical markers associated with hepatic and renal functions and enzymatic activities were quantitatively assessed to evaluate potential physiological and metabolic alterations.

Results: Biochemical analysis revealed significant alterations in liver and kidney function markers in rats exposed to contaminated water. Liver alkaline phosphatase (ALP), aspartate aminotransferase (AST), and γ-glytamyl transferase (GGT) activities were significantly decreased (p < 0.05), while serum ALP, AST and GGT levels were significantly elevated (p < 0.05) in the contaminated water group compared to control. Serum urea and creatinine levels were significantly higher in rats exposed to contaminated water (90 ± 0.08 mg/dL and 21.73 ± 4.03 mg/dL, respectively) compared to the control group (43 ± 0.13 mg/dL and 16.37 ± 1.97 mg/dL, respectively; p < 0.05). Conversely, administration of chitosan-AgNP-treated water significantly reduced these elevations, bringing the values closer to control levels. Bacteriological analysis showed a drastic reduction in total coliform and fecal counts from 1.44 × 10⁷ CFU/mL and 7.2 × 10⁶ CFU/mL, respectively, to 0 CFU/mL after 27 days of chitosan-AgNP treatment.

Conclusion: The findings suggest that chitosan-AgNP treatment significantly reduces bacterial load in water and positively affects selected biochemical parameters of albino rats, indicating its potential as a water treatment option.

Vitamin D administration in type 1 diabetes and its impact on T lymphocyte subsets

Mamdouh Allahyani — 2025-05-30

Purpose: To investigate the effect of vitamin D supplementation on glycated hemoglobin A1c (HbA1c); CD3+, CD4+, CD8+, CD4+/CD25+, and CD8+/CD25+ ratios. Methods: Thirty mice were equally assigned to three cohorts: control, untreated T1 diabetic (T1), and T1 diabetic treated with vitamin D for 4 months. Body weight, blood glucose levels, HbA1c percentages, and lipid profiles were measured in mice in each of the three groups. Additionally, total lymphocytes and CD4+, CD3+ cells, CD8+ cells, CD4+/CD25+, and CD8+/CD25+ ratios were assayed using flow cytometry in all mice. Results: Data showed significantly lower blood glucose levels, HbA1c levels, and lipid profiles (p < 0.0001); total lymphocyte counts (p < 0.05), and counts of CD3+ (p < 0.05), CD4+, and CD8+ cells (p < 0.0001) in vitamin-D-treated diabetic mice than in the untreated diabetic mice. In contrast, there were significantly higher CD4+/CD25+ and CD8+/CD25+ ratios in treated mice with diabetes (p < 0.01). Conclusion: Vitamin D may have promising immunomodulatory properties that could help mitigate the harmful effects of T1DM.

Comparison between the effect of Commiphora gileadenesis and metformin on blood glucose levels and lipid profile in diabetic mice

Ayman Alhazmi — 2025-05-30

Purpose: To investigate the effect of C. gileadensis on blood glucose levels and lipid profiles in diabetic mice.

Methods: A total of 60 male mice were divided randomly into 6 groups of 10 each. Type 2 diabetes was induced with streptozotocin (55 mg/kg body weight) intraperitoneally. The experiment consisted of six groups: negative control, diabetic non-treated, and diabetic groups treated with 200 mg/kg body weight per day of sap, methanolic, and acetone extracts of C. gileadensis orally for 4 months. Furthermore, the sixth group was diabetic mice treated with 55 mg/kg of metformin daily by intragastric gavage for 4 months. After 4 months of treatment, blood samples were collected from the retro-orbital venous plexus in non-heparinized tubes from all mice and random blood glucose levels, lipid profile, and hemoglobin A1c (HbA1c) were evaluated.

Results: The random blood glucose levels, triglyceride, total cholesterol, and low-density lipoprotein (LDL) levels were significantly (p < 0.0001) reduced in diabetic mice treated with C. gileadensis sap, a methanolic extract of C. gileadensis, and an acetone extract of C. gileadensis compared with non-treated diabetic group. Moreover, diabetic mice treated with C. gileadensis sap had significantly (p < 0.01) lower total cholesterol and LDL compared with those treated with metformin. Diabetic mice treated with C. gileadensis sap, methanol, and acetone extract had significantly (p < 0.0001) higher HDL levels compared to untreated diabetic group. However, C. gileadensis sap significantly increased HDL in diabetic mice compared to metformin (p < 0.01).

Conclusion: The sap, methanolic and acetone extracts of C. gileadensis normalize random blood glucose, HbA1c, and lipid profiles in diabetic mice. The sap of C. gileadensis exhibits greater efficacy compared to other extracts and metformin in reducing random blood glucose levels and improving lipid profiles.

Inhibitory effect of emododstat on respiratory syncytial virus

San Li — 2025-05-30

Purpose: To identify anti-respiratory syncytial virus (RSV-A) candidates from the pool of approved drugs through drug repositioning and preliminary elucidation of their mechanisms of action.

Methods: Human laryngeal epithelial carcinoma cells (HEp-2) were infected with RSV-A (GenBank: PQ594188). The cytopathic effect (CPE) was used to conduct an initial screening of 1213 compounds from the drug library. For the selected candidate drug, emvododstat, a dihydroorotate dehydrogenase (DHODH) inhibitor, further analysis was performed with Cell Counting Kit-8 (CCK-8) assay to determine the viral copy number using absolute quantification and to measure the half-maximal effective concentration (EC50), half-maximal cytotoxic concentration (CC50), and selectivity index (SI = CC50/EC50). A time-of-addition assay (TOA) was conducted to determine the phase of the antiviral action, and the potential mechanism involved was determined, in addition to the DHODH inhibitory properties of the drug.

Results: Emvododstat exhibited potent anti-RSV-A activity with an EC50 of 5.23 nmol/L and SI > 19,120 thereby outperforming Ribavirin (EC50 = 14.5 μmol/L, SI = 52). The TOA assays revealed that Emvododstat primarily acted during the post-entry phase, with minimal inhibition of viral entry.

Conclusion: This study has demonstrated, for the first time, that Emvododstat exerts nanomolar inhibitory activity and high selectivity against RSV-A viruses. This finding highlights the potential of drug repositioning strategies in antiviral drug development. Although its mechanism of action has not been fully clarified, the high selectivity and low cytotoxicity of Emvododstat provide an important basis for its clinical application.

Effect of vitamin E on testosterone and dihydrotestosterone concentrations in Wistar rats administered artemether/lumefantrine and ciprofloxacin

Jessie Ndem — 2025-05-30

Purpose: To investigate the effect of vitamin E on testosterone and dihydrotestosterone concentrations in Wistar rats administered artemether/lumefantrine and ciprofloxacin.

Methods: Thirty-five albino Wistar rats (average weight of 200 g) were randomly divided into 7 groups of 5 rats per group. Group 1 was the normal control, while Groups 2 and 3 were administered 8 mg/kg artemether/lumefantrine and 7.14 mg/kg ciprofloxacin, respectively. Group 4 received artemether/lumefantrine and ciprofloxacin (AL-CIPRO) concomitantly, while Groups 5, 6 and 7 received Vitamin E in addition to AL, CIPRO and AL-CIPRO combinations, respectively. Plasma testosterone and dihydrotestosterone concentrations and testicular weight were determined.

Results: The concentrations of testosterone and dihydrotestosterone decreased non-significantly (p > 0.05) following separate administration of AL and CIPRO but significantly (p < 0.05) with concomitant administration compared with control. Vitamin E, in combination with the drugs, significantly (p < 0.05) increased testosterone and dihydrotestosterone concentrations compared to groups without vitamin E. Testicular weight exhibited the same pattern of result.

Conclusion: Artemether/lumefantrine and ciprofloxacin administration, singly and in combination, may induce reproductive toxicity, which could be due to free radicals generated from their metabolism. Vitamin E co-administration with the drugs (AL, CIPRO and AL-CIPRO) demonstrates an ameliorative effect against toxicity induced by the drugs, which may be attributed to its free radical scavenging ability.

Comparative effect of chronic administration of artemether/lumefantrine and chloroquine on selected male reproductive indices

Emmanuel Nnamonu — 2025-05-30

Purpose: To evaluate the effect of administration of artemether/lumefantrine and chloroquine on some male reproductive parameters.

Methods: Sixty adult male albino rats, aged 12 – 13 weeks and weighing between 186 – 199 g, were assigned into five groups: control group and four other groups administered 2/12 mg/mL of artemether/lumefantrine (ART/LUM), 4/24 mg/mL of ART/LUM, 10 mg/mL chloroquine (CHLQN) and 20 mg/mL CHLQN, respectively. Treatment was carried out at 48 h intervals for 28 days, followed by assessment of gonadosomatic index, testicular and epididymal sperm cell counts, testicular histology, testis epithelial thickness and tubular diameter according to standard methods.

Results: Artemether/lumefantrine exposure did not significantly (p > 0.05) affect testes relative weight, epididymis tail weights and sperm count per gram epididymis, but the sperm count per gram testis and sperm count per testis were increased. Chloroquine showed no significant (p > 0.05) impact on most parameters except for reduction in testis weight in the high-dose group. Histomicrographs of testicular tissue showed normal structure in control and ART/LUM-treated groups, while CHLQN-treated groups exhibited moderate testicular degeneration.

Conclusion: Artemether/lumefantrine does not adversely affect male reproductive health based on the parameters assessed, but chloroquine administration induces mild adverse histological changes. The study opens avenues for further research into mitigating potential reproductive side effects associated with antimalarial treatments.

Structural and functional response of the genital tract to paraquat (PQ) dichloride exposure in female Wistar rats

Ehizokhale Ehebha — 2025-05-30

Purpose: To investigate the structural and functional response of genital tract to paraquat (PQ) exposure in female Wistar rats. Methods: A total of 24 healthy female Wistar rats weighing between 150 - 180 g were grouped randomly into four equal groups. Group 1 served as control (received normal saline) while Groups 2, 3 and 4 were referred to as study groups and received 1, 5, and 10 mg/kg/bw PQ, respectively, once daily for 42 days. Blood samples (5 mL) were collected by cardiac puncture and centrifuged. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen, and progesterone were quantified. The animals were sacrificed by cervical dislocation and the ovary and uterus were excised and processed using H & E staining. Results: Paraquat (PQ) disrupted the histoarchitecture of the ovary and uterus by inducing ovarian atrophy and chronic endometritis. Furthermore, PQ significantly increases serum levels of LH, FSH, estrogen, and progesterone compared to control (p < 0.05). Conclusion: Paraquat (PQ) induces ovarian atrophy, chronic endometriosis, and increases levels of LH, FSH, estrogen, and progesterone. Further large-scale studies in higher animals may be needed to validate these findings and provide a regulatory framework for PQ administration.

Pharmacognostic, phytochemical, antioxidant and toxicological properties of aqueous extract of Telfairia occidentalis Hook. F. leaves

Patience Ugwu — 2025-05-30

Purpose: To determine the phytochemical composition, toxicological profile, pharmacognostic and therapeutic potential of aqueous extract of Telfairia occidentalis (T. occidentalis) in phenylhydrazine-induced oxidative stress in Wistar rats.

Methods: The pharmacognostic and phytochemical parameters were assessed using established analytical standards. Acute toxicity study (LD50) was evaluated on Wistar rats using Lorke’s method, while the subacute toxicity was conducted using liver markers (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)) and kidney function tests (creatinine, uric acid, and urea). Furthermore, antioxidant activity was investigated by spectrophotometrically monitoring stress markers (malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase activity in vivo.

Results: Aqueous extract of T. occidentalis at 100 - 400 mg/kg significantly reduced stress markers compared to non-treated group, surpassing standard Orheptal at 50 mg/kg (p < 0.05). The extract showed very high LD50 (> 5000 mg/kg) with no marked adverse effect on hepatic and renal functions. Phenolic content was highest in the extract (30.673 mg/g).

Conclusion: Aqueous extract of T. occidentalis reduces oxidative stress, thus highlighting its promising role as a natural blood tonic and antioxidant. The high number of phenolic compounds in T. occidentalis is largely responsible for its activities.

Genetic association of SCN1A gene polymorphisms and efficacy of anti-seizure medications

Yusra Abdulqader — 2025-05-30

Anti-seizure medications (ASMs) are crucial in the management of seizures; however, significant variability in treatment responses exists, even among patients with similar seizure types and clinical histories. Developing an objective biomarker that could consistently predict efficacy of ASMs poses a substantial challenge in transforming the landscape of epilepsy treatment. Currently, healthcare providers tend to rely on trial-and-error methods when selecting ASMs, which constitutes a time-consuming process and may delay the use of alternative non-pharmacological interventions, such as ketogenic diets, epilepsy surgery and neuromodulating therapies. Predicting the efficacy of ASMs through pharmacogenetic studies that explore the relationship between ASMs and genetic variations related to their mechanisms of action offers prognostic insights into treatment responses, potentially leading to improved outcomes. While sodium channel subunit (SCN) genes, along with various ion channels and receptors, have been extensively investigated as therapeutic targets, findings have been inconsistent. This is likely due in part to differences such as variations in defining drug responses, types of ASM combinations used, and the genetic variants tested. Nevertheless, these studies highlight the significant influence of genetic variations on the activity of ASMs and subsequently on predictions for expectable therapeutic responses. Advances in sequencing technologies have resulted in extensive genetic datasets that could enhance the accuracy of ASMs' response predictions. This review examines the pharmacogenetic associations of sodium channel 1A subunit (SCN1A) gene polymorphisms and the efficacy of ASMs in different ethnicities.

Modulating xanthine oxidase activity: A promising therapeutic strategy to reduce the severity and associated inflammatory reactions in malaria infection

Mukhtar Lawal — 2025-05-30

Malaria is a severe and often fatal disease that affects millions of people each year. More than fifty percent of human population worldwide is at risk of malaria. While antimalarial therapy is targeted at parasite elimination, the pathogenesis of malaria infection is particularly oxidative and inflammatory, involving the generation of reactive oxygen species (ROS). Xanthine oxidase (XO) is believed to be a potent source of ROS during malaria infection. ROS generated by this enzyme are a major contributor to oxidative stress and inflammation development. Consequently, free radical production and oxidative stress are responsible for the numerous complications in severe malaria. Therefore, effective treatment of the disease will require, in addition to the elimination of the parasite, a mechanism that reduces severe oxidative stress and inflammatory reactions associated with the disease. The pathophysiologic role of this enzyme is thus a potential target in malaria infection. Inhibition of XO activity is clinically effective in treating many inflammatory diseases, such as gout and prevention of cardiovascular disorders, therefore making this enzyme an attractive candidate for treating malaria inflammation. The present review focuses on the role of XO in malaria pathogenesis and the potential of enzyme inhibition as a therapeutic strategy to mitigate the severe inflammatory responses during malaria infection. Ultimately, the severity, complications and death associated with the disease are ameliorated by reducing the intensity of the inflammatory reactions during malaria infection.