Efficacy Profile Research Articles

Long-Term Effectiveness and Safety of Ustekinumab in Crohn’s Disease: Results from a Large Real-Life Cohort Study

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn’s disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST’s long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients. Methods: This was a multicenter, retrospective, observational cohort study that included both naïve and biologic-experienced patients treated with UST who achieved clinical remission or clinical response after at least one year of treatment. Clinical activity was scored according to the Harvey–Bradshaw Index (HBI). The primary endpoints were the maintenance or achievement of clinical remission after a further 12-month period of treatment, defined as an HBI of ≤5, and safety. Other endpoints included steroid-free remission, mucosal healing (MH), steroid discontinuation, and the need for treatment optimization during the follow-up. Results: Out of 562 CD patients, after an overall 24-month follow-up, clinical remission was present in 450 (80.0%) patients, and at 12 months, clinical remission was observed in 417/437 (95.4%) patients; 33/125 (26.4%) showed clinical response at 12 months (p = 0.000). A total of 38/103 (36.9%) patients achieved MH. Only 2.1% (12/562), 3% (17/562), and 1.1% (6/562) of patients required surgery, optimization, and re-induction, respectively. Adverse events occurred in eight patients (1.42%). According to a multivariate analysis, the only predictor of long-term remission was the presence of remission at the 12-month follow-up (p = 0.000). Conclusions: Long-term treatment with UST presents good efficacy and safety profiles in CD patients, especially for patients who achieve remission after one year.

Pharmacokinetics of Tarlatamab, a Delta-Like Ligand-3 (DLL3) Targeted Half-Life Extended Bispecific T-Cell Engager (BiTE®) Immunotherapy in Adult Patients with Previously Treated Small-Cell Lung Cancer: Results from DeLLphi-300, a Phase I Multiple-Dose-Escalation Study.

Tarlatamab binds to delta-like ligand 3 on cancer cells and cluster of differentiation-3 on T cells, leading to T-cell-mediated tumor lysis, and has demonstrated a promising safety and efficacy profile in patients with previously treated small-cell lung cancer (SCLC). Here, we present pharmacokinetic results from DeLLphi-300 (NCT03319940), an ongoing international, open-label, first-in-human study in previously treated adult patients with SCLC. Multiple escalating doses of tarlatamab were administered every 2 weeks (Q2W; 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mg) in a 28-day cycle. To reduce the risk of cytokine-release syndrome, starting at the 3 mg dose level, a step dose regimen was employed consisting of a 1 mg infusion on cycle 1 day 1 (C1D1), followed by the target dose on C1D8, C1D15, and Q2W thereafter. All doses were infused over 1 h. Other tarlatamab dosing regimens were also explored, either for patient convenience (every 3 weeks) or to mitigate cytokine-release syndrome (extended intravenous infusion over a period of 3 days). Intensive pharmacokinetic samples were collected during cycles 1 and 2, and additional samples for pharmacokinetic and immunogenicity measurement were collected at regular intervals in later cycles. Pharmacokinetic data were analyzed using noncompartmental analysis, and antidrug antibody (ADA) incidence, including any effect on tarlatamab pharmacokinetic parameters, was summarized. Pharmacokinetic data were available from 203 patients. The median age was 62 years (range 32-80), and 55.7% (n = 113) of patients were male, 78.3% (n = 159) were white, and 8.3% (n = 17) were of Japanese descent. Following intravenous infusion, serum tarlatamab concentrations declined with time in a biphasic manner. Serum exposures increased in an approximately dose-proportional manner across the evaluated target dose range with a mean (standard deviation) estimated terminal phase elimination half-life of 5.8 (1.6) days, and steady state achieved by approximately C2D15. Of the 183 evaluable patients, 12 (6.6%) developed treatment-emergent ADAs; the distribution of dose-normalized serum concentrations were similar between patients who were ADA positive and ADA negative. In addition, the distribution of exposures was comparable in Japanese and non-Japanese patients. In patients with previously treated SCLC, tarlatamab demonstrated dose-proportional pharmacokinetic and extended half-life characteristics that support a Q2W dosing interval. Neither Japanese race nor ADA had a clinically relevant impact on exposures.

Enhancing the Cytotoxic Effects of Carboplatin and Cisplatin on Liposomes in Oral Cancer Cells with Curcumin

Background: Oral squamous cell carcinoma remains challenging to treat effectively with conventional chemotherapy, leading researchers to explore synergistic combinations to enhance therapeutic outcomes. Combining curcumin with platinum-based drugs, such as cisplatin and carboplatin, has demonstrated potential in enhancing cytotoxic effects. However, limited studies have explored these combinations’ efficacy and sustained release profile in liposomal form specifically for oral cancer. This study investigates the enhanced cytotoxic effects of cisplatin-curcumin and carboplatin-curcumin nanoliposome formulations on CAL 27 oral cancer cells. Methods and Materials: Nanoliposomes encapsulating cisplatin or carboplatin with curcumin were formulated and characterized by particle size, zeta potential, and polydispersity index (PDI) to ensure optimized delivery properties. Particle sizes of the cisplatin and carboplatin nanoliposomes ranged from 175 to 187 nm, with a zeta potential greater than -30 mV, indicating good stability, and PDI values less than 0.48, suggesting uniform particle size distribution. In vitro cytotoxicity was assessed using the MTT assay at 24, 48, and 96 hours across different curcumin concentrations. Results: Cisplatin-curcumin and carboplatin-curcumin nanoliposome formulations demonstrated significantly increased cytotoxicity in CAL 27 cells compared to control groups. Drug release studies indicated a sustained release profile, with approximately 22% of cisplatin and 28% of carboplatin released over 52 hours, which may prolong therapeutic effects by maintaining drug availability within the cancer cells. Conclusion: The findings suggest that cisplatin-curcumin and carboplatin-curcumin nanoliposomal formulations enhance the cytotoxic effects of these chemotherapeutic agents while providing a stable, sustained release profile.

Comparison of topical potassium hydroxide 5% solution with cryotherapy in the treatment of patients with genital warts: A randomized controlled clinical trial.

Given the therapeutic challenge of wart treatment and the need for an ideal treatment that is effective, noninvasive, cost-effective, and has minimal side effects, this study aims to compare the local impact of a 5% potassium hydroxide (KOH) solution with cryotherapy, the current standard treatment for genital warts. Two groups, each consisting of 49 patients: the first group was treated with a daily topical application of 5% KOH solution using a swab, while the second group underwent cryotherapy in two 5-20 s freeze-thaw cycles. Before treatment, patient demographic data and number of lesions were recorded. Follow-up visits were conducted at four-week intervals for 12 weeks, during which the number of lesions, time to complete recovery, and skin-related side effects were examined and recorded, ensuring comprehensive data collection. A total of 98 patients (average age: 28.40 ± 7.34 years), 55 cases (55.1%) being female and 43 cases (43.9%) being male. Importantly, there was no significant difference in terms of gender (p = .684), education (p = .533), and marital status (p = .703) between the two study groups. Further, no significant difference in previous infection history (p = .493) and partner infection (p = .098) was identified. There was no significant difference in terms of treatment response (p = .510) and relapse (p < .999) between the two KOH and cryotherapy study groups. The study found no significant differences in treatment response, relapse rates, or side effects between using 5% potassium hydroxide solution and cryotherapy for genital wart treatment. These findings suggest that both modalities offer comparable efficacy and safety profiles, providing clinicians with valuable options in tailoring treatment approaches for patients with genital warts.

Molecular simulations and machine learning methods for the identification of novel aurora A kinase inhibitors

Aurora A kinase (AAK) is a serine/threonine kinase that stands out as a crucial regulator of mitosis, the complex process of cell division. Notably, the protein AAK plays vital roles in cell cycle regulation and encompasses centrosome maturation, spindle assembly, and chromosome segregation. All such functionalities are essential for ensuring accurate daughter cell formation. Deregulation of AAK expression and activity has been linked to various human diseases, particularly cancer. However, AAK's significance extends beyond normal cellular function. Increased expression or activity of AAK has been implicated in the development and progression of several human cancers. AAK’s critical role in cell division and its association with cancer make it a prominent drug target. Herein, series of advance computational approaches was utilized including multi-step molecular docking through AutoDock Vina and PLANTS docking to screen ChemDiv kinase-specific inhibitor library against AAK. Absolute binding energy was estimated, and finally, a molecular dynamics simulation study was conducted to screen out three hit compounds. Both docking studies revealed perfect binding of all identified ligands in active site pockets of AAK protein with similar amino acids of active sites as compared with standard BindingDB_50433632 compound and co-crystal ligand VX-680 binding mode of AAK protein. Therefore, it can be concluded that computational drug discovery approaches are meticulously implemented to identify potential AAKs inhibitors/modulators, and credential of the work was substantiated through the identification of three potential AAKs inhibitors/modulators that may hold significant promise for improving cancer management, however, need extensive biological assays or pre-clinical trials for assessing the efficacy profile of the identified compounds.

Discovery of Pyridine-2-Carboxamides Derivatives as Potent and Selective HPK1 Inhibitors for the Treatment of Cancer.

Hematopoietic progenitor kinase 1 (HPK1) has emerged as an attractive target for immunotherapy due to its critical role in T cell activation and proliferation. The major challenge in developing HPK1 inhibitors lies in balancing kinase selectivity, pharmacokinetic (PK) properties, and therapeutic efficacy. In this study, we report a series of pyridine-2-carboxamide analogues demonstrating strong HPK1 inhibitory activity in enzymatic and cellular assays, along with good kinase selectivity. Among these analogues, compound 19 showed good in vitro HPK1 inhibitory activity, excellent kinase selectivity (>637-fold vs GCK-like kinase and >1022-fold vs LCK), and robust in vivo efficacy in the CT26 (tumor growth inhibition (TGI) = 94.3%, 2/6 CRs) and MC38 murine colorectal cancer models (TGI = 83.3%, 1/6 complete response) when administered in combination with anti-PD-1. Compound 19 also demonstrated adequate in vitro ADME and in vivo PK properties, displaying good oral bioavailability across multiple species (F % = 35-63). These findings summarize our compound's favorable safety and efficacy profiles, justifying its testing in future translational studies.

Phase I Trial to Assess the Safety, Tolerability, and Preliminary Efficacy of OBI-858 for Treatment of Glabellar Lines.

OBI-858 is a brand-new botulinum Type A complex toxin with a specific molecular weight of 760kDa intended for development for both aesthetic and therapeutic applications.This is a phase I, dose-escalation study to evaluate the safety and preliminary efficacy of OBI-858 in subjects with moderate to severe glabellar lines. Each subject received OBI-858 by intramuscular injections with an assigned dose (10 U, 20 U, and 30 U). The safety and preliminary efficacy were evaluated at each of the in-person visits. A total of 36 subjects (12 subjects per cohort) were enrolled. The response rates (≥ 1 point) for all groups at maximum frown were assessed at week 4 were 100%. The initial improvement for 30 U occurred at day 3. Response rates revealed benefits lasting 4-6months or longer. Subject satisfaction at week 4 was high in all groups. Adverse effects were mild and infrequent. Among them, one subject had drug-related AE, and one subject had grade ≥ 3 unrelated AE. This study demonstrated that OBI-858 is well tolerated and showed preliminary efficacy. Overall, the OBI-858 has a clinically favorable profile of safety and efficacy that warrants proceeding to the next studies.

Advancing Glaucoma Treatment During Pregnancy and Breastfeeding: Contemporary Management Strategies and Prospective Therapeutic Developments

The management of glaucoma in pregnancy and breastfeeding requires a careful evaluation of treatment choices to guarantee the well-being of both the mother and the developing fetus. This review explores the intricacies of controlling glaucoma in pregnant and breastfeeding women, including a comprehensive overview of existing glaucoma treatment methods, clinical guidelines, and future therapeutic approaches. The efficacy and safety profiles of traditional treatment approaches, such as topical and systemic medicines and surgical treatments, are evaluated specifically about their use during pregnancy and breastfeeding. The significance of personalized treatment programs to achieve a balance between controlling intraocular pressure and ensuring the safety of the fetus and the newborn and the importance of a multidisciplinary approach that includes ophthalmologists, obstetricians, and other healthcare experts are underlined. Non-pharmacological therapies, lifestyle adjustments, and the importance of patient education in the management of glaucoma during pregnancy and the post-partum period are also examined. Advancing our comprehension of and strategy toward glaucoma can reduce the effects of glaucoma on maternal, fetal, and newborn well-being.

A systematic review on the efficacy of GLP-1 receptor agonists in mitigating psychotropic drug-related weight gain.

Many psychotropic drugs are highly associated with related weight gain. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established anti-obesity and glucose-lowering agents. Preliminary evidence also indicates they are fit for purpose in mitigating psychotropic drug-related weight gain (PDWG). This systematic review aims to synthesize the extant evidence from randomized controlled trials (RCTs) on the effects of GLP-1RAs on weight change in persons experiencing PDWG. Online databases (ie, PubMed, OVID Medline, Google Scholar) were searched to identify relevant studies from inception to January 1, 2024. Articles were screened by title, abstract, and full-text by three independent reviewers against inclusion and exclusion criteria. We identified six studies with participants aged ≥18 (n=374) that were eligible for inclusion in our systematic review. Most studies reported a significant and clinically meaningful effect of GLP-1RAs on anthropometrics and/or metabolics. All RCTs replicated the finding of modest or greater effects of GLP-1RAs; the most studied agents were liraglutide and exenatide. There was insufficient literature to conduct a meta-analysis. Evidence suggests that GLP-1RAs are effective in mitigating weight gain in persons prescribed psychiatric medication. It is hypothesized that GLP-1RAs may moderate weight change in persons prescribed psychiatric medication through direct effects on metabolism and cognitive processes implicated in hunger/satiety. Future studies should aim to explore the long-term safety, tolerability, and efficacy profiles of various GLP-1RAs in the treatment and prevention of abnormal weight and metabolic homeostasis in psychiatric populations.

A Multicenter Randomized Double-Blind Vehicle-Controlled Parallel Group Phase 2 Study Evaluating the Efficacy and Safety of GN-037 Cream in Patients with Mild-to-Moderate Plaque Psoriasis.

Topical therapies are used in almost all patients with psoriasis. A novel fixed topical combination cream (GN-037) with a lower concentration (0.0356%) of clobetasol 17-propionate (CP) was developed together with urea, salicylic acid, and retinoic acid to provide a better benefit-risk ratio. The present multicenter randomized double-blind vehicle-controlled parallel group phase 2 study aimed to investigate the efficacy and safety of GN-037 in patients with mild-to-moderate plaque psoriasis (MMPP). Patients (n = 190) were randomized (2:2:1) to receive GN-037 or CP or vehicle (V) cream twice daily to a selected target body lesion for 4weeks. The primary endpoint was treatment success defined as percentage of patients with at least two-grade improvement in Investigator's Global Assessment Score (IGA) and IGA score equal to 0 or 1 evaluated at weeks 2, 4, 6, and 8 in each arm compared with baseline. Treatment-emergent adverse events (TEAEs) and safety were evaluated throughout the study. GN-037 demonstrated statistically significant superiority over V throughout the study. At week 4, treatment success was achieved in 37.9% of patients in the GN-037 arm compared with 29.2% and 9.1% in the CP and V arms, respectively. At least two-grade improvement compared with baseline was achieved by 57.6%, 72.7%, and 80.3% of the patients in the GN-037 arm for erythema, plaque elevation, and scaling, respectively. The mean changes in affected BSA were -2.1 ± 2.9, -1.8 ± 2.4, and -0.5 ± 1.6 in the GN-037, CP, and V arms, respectively. The TEAEs were similar among the arms and the most frequently observed TEAEs were Psoriasis Area and Severity Index (PASI) increase in all arms. GN-037 was more effective than V in achieving primary and all secondary endpoints throughout the study. Safety data did not reveal any new safety concerns with the combination cream product. Therefore, 4weeks of GN-037 treatment demonstrated an excellent efficacy and safety profile in patients with MMPP. ClinicalTrials.gov identifier, NCT05706870.

Efficacy and safety of daratumumab for the treatment of refractory/relapsed multiple myeloma. A systematic review of meta-analyses.

Several meta-analyses (MAs) of the efficacy and safety of daratumumab in refractory/relapsed multiple myeloma (RRMM) exist. They include different types of populations, Daratumumab regimens, and outcomes. Moreover, there is a wide variation in methodological quality and risk of bias. This study aimed to conduct a systematic review of MAs to summarize the literature on the efficacy and safety profile of daratumumab use in RRMM, and also provide an assessment of the quality and risk of bias of the MAs if sufficient data is available. The literature databases Pubmed, Embase, Web of Science, and Cochrane were searched since inception. The quality of methodology was assessed by the AMSTAR-2 tool, and the risk of bias was assessed by the ROBIS tool. Eight MAs were included in the SR. Most studies reported ORR and CR improvement by adding daratumumab to the chemotherapy regimen. Five MAs reported improvement in PFS in daratumumab-based regimens compared to non- daratumumab-based regimens. Only two MAs reported molecular response, favoring daratumumab. Dara was associated with adverse drug events (ADEs), including pneumonia and diarrhea. Conflicting evidence regarding hematological ADEs association with daratumumab exists. The overall quality of the studies is poor, but the MAs had a low risk of bias overall. Despite including low-quality MAs, this SR provides a summary that simplifies clinicians' access to efficacy and safety outcomes of daratumumab in RRMM patients. Future studies are required to reduce the uncertainty and produce higher-quality Mas, particularly regarding daratumumab's safety.

Unique pharmacological properties of etrasimod among S1P receptor modulators.

Etrasimod (ADP334) is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis and in development for the treatment of immune-mediated inflammatory diseases. Interaction between S1P and its five receptor subtypes (S1P1-S1P5) plays a role in several physiologic systems, including the cardiovascular and immune systems. Since differences in S1PR binding and downstream intracellular signaling could contribute to distinct profiles of drug efficacy and safety, we directly compared the S1P1-5 selectivity profile of etrasimod to three marketed S1PR modulators: fingolimod, ozanimod, and siponimod. Using both heterologous expression systems and human umbilical vein endothelial cells that spontaneously express S1P1, we profiled key S1P1 downstream signaling pathways and found that etrasimod had similar potency to the other tested S1PR modulators in promoting β-arrestin recruitment and S1P1 internalization. However, etrasimod was notably less potent than other S1PR modulators in assays measuring S1P1-mediated G protein activation (GTPγS binding and cAMP inhibition). Relatively lower potency of etrasimod in inducing G protein signaling corresponded to significantly diminished activation of human cardiac G protein-coupled inwardly rectifying potassium channels when compared to ozanimod. Together with pharmacokinetic properties, this hell profile of etrasimod may contribute to the positive benefit risk profile of etrasimod observed during the phase III ELEVATE UC 52 and ELEVATE UC 12 trials in patients with moderately to severely active ulcerative colitis.

A meta-analysis and systematic review based on perioperative management of elderly patients: is ciprofol an alternative to propofol?

With the rising number of elderly surgical patients, selecting an appropriate anesthetic tailored to their specific needs is essential. Ciprofol, a novel intravenous anesthetic, has garnered attention due to its low injection pain rate and minimal impact on the circulatory system. This meta-analysis aims to examine the efficacy and safety profile of ciprofol during perioperative management of elderly patients. Comprehensive searches of PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases from inception to March 23, 2024, were conducted. Eligible studies were included, data extracted, quality assessed using the ROB2 tool, and analyses performed with Stata 17.0. Analysis of eleven randomized controlled trials (RCTs) comprising 1715 patients demonstrated that ciprofol outperformed propofol regarding injection pain (RR: 0.13, 95% CI: 0.09-0.20, p < 0.001), hypotension (RR: 0.72; 95% CI: 0.56-0.94; p = 0.014), bradycardia (RR: 0.64, 95% CI: 0.48-0.85, p = 0.002), respiratory depression (RR: 0.29, 95% CI: 0.19-0.43, p < 0.001), hypoxemia (RR: 0.38, 95% CI: 0.26-0.55, p < 0.001), and body movement (RR: 0.73, 95% CI: 0.56-0.96, p = 0.022). No significant differences were observed in induction time(SMD: 0.11,95% CI: -0.39-0.61, p = 0.655), sedative success rate(RR:1.01,,:95% CI:0.97-1.06, p = 0.669)), time of leaving the operating room(SMD-0.21,95% CI: -0.83-0.40, p = 0.497), bucking(RR:0.56,:95% CI:0.27-1.17, p = 0.134)), nausea and vomiting(RR:0.69,95% CI:0.43-1.11, p = 0.143)). Ciprofol demonstrates comparable efficacy to propofol in general anesthesia for elderly patients, with an enhanced safety profile, making it a viable clinical alternative. Further well-designed large RCTs are required to substantiate its safety profile.

Effectiveness, safety, and patient-reported outcomes of treatment with bictegravir/emtricitabine/tenofovir alafenamide fixed dose combination in people living with HIV in Argentina: the BICTARG cohort.

Real-world data on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) fixed-dose combination from resource-constrained settings like Latin America are limited. We conducted an observational retrospective cohort study of treatment-naive (TN, n=315) and treatment-experienced (TE, n= 2356) people living with HIV prescribed BIC/FTC/TAF in Argentina from 10/2019 to 12/2021, with 24 and 48-week follow-up data analyzed for virological suppression, persistence, safety, and metabolic parameters. Patient-reported outcomes were assessed via across-sectional online survey. Baseline characteristics: median age 45 years, 72.2% male, 99.6% Hispanic/Latino ethnicity. Treatment per sistence at 48 weeks was 99.3% (TN) and 99.5% (TE). Virological suppression rates (<200/<50 copies/mL) at 24 weeks were 97.4/88% (TN) and 99/97% (TE). At 48 weeks were 100/92% (TN) and 99/97% (TE). In the TE group, triglycerides decreased with no other lipid changes. In TN, mild total/LDL/HDL cholesterol increases occurred. eGFR mildly decreased in both groups. The online survey (n=536) showed 91.5% reported no medication concerns. Median quality of life scores were 90 (TN) and 88 (TE). Most reported no self-care, activity, mobility, pain/discomfort, or anxiety/depression issues. BIC/FTC/TAF demonstrated high persistence, safety, virological efficacy, and favorable metabolic profile over 48 weeks. The cross-sectional survey indicated high treatment satisfaction and good quality of life in this cohort from Argentina.

Rhodanine-Piperazine Hybrids as Potential VEGFR, EGFR, and HER2 Targeting Anti-Breast Cancer Agents.

Breast cancer is one of the most common malignancies affecting women worldwide, with a significant need for novel therapeutic agents to target specific molecular pathways involved in tumor progression. In this study, a series of rhodanine-piperazine hybrids were designed, synthesized, and evaluated for their anticancer activity, targeting key tyrosine kinases such as VEGFR, EGFR, and HER2. Biological screening against breast cancer cell lines (MCF-7, MDA-MB-231, T47D, and MDA-MB-468) revealed 3 of the 13 tested compounds as the most potent, with 5-({4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}methylidene)-2-thioxo-1,3-thiazolidin-4-one (12) showing the strongest activity, particularly against the MCF-7 and MDA-MB-468 cell lines. Molecular docking studies indicated favorable binding interactions of compound 12 and its 3-phenyl-2-thioxo-1,3-thiazolidin-4-one analogue (15) with HER2, VEGFR, and EGFR, and molecular dynamics simulations further confirmed their stable binding to HER2. These findings highlight the potential of rhodanine-piperazine hybrids as promising leads for developing new anticancer agents targeting breast cancer, particularly HER2-positive subtypes. Further structural optimization could enhance their efficacy and therapeutic profile.

Comparative Study of Antimicrobial Efficacy and Phytochemical Profiles of Ethanol and n-Hexane Extracts from the Roots of Ixora coccinea Linn

The root extracts of Ixora coccinea were evaluated for their phytochemical composition, antibacterial activity, and minimum inhibitory concentration (MIC) against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. Quantitative phytochemical analysis was conducted to determine the levels of terpenoids, flavonoids, alkaloids, tannins, and saponins. Thin Layer Chromatography (TLC) was used to confirm the presence of bioactive components in the extracts under different solvent systems, followed by antibacterial susceptibility tests using the disc diffusion method. The MIC was determined through serial dilution to identify the lowest concentration that inhibited bacterial growth. Quantitative phytochemical analysis showed that the ethanol extract contained 14.80% flavonoids, 6.00% alkaloids, 1.20% saponins, 1.80% terpenoids, and 0.03% tannins. In contrast, the n-hexane extract had higher terpenoid content (3.40%) but lower flavonoids (5.20%) and alkaloids (2.10%). Thin Layer Chromatography (TLC) analysis under varying solvent systems showed different Rf values, with the ethanol extract displaying more diverse spots, indicating a richer variety of bioactive compounds. Antibacterial susceptibility tests revealed that the ethanol extract produced larger inhibition zones (10 ± 0.4–28 ± 1.0 mm) than the n-hexane extract (6 ± 0.2–26 ± 0.8 mm). MIC results indicated that ethanol extract inhibited E. coli and S. aureus at 50 mg/L and B. subtilis at 25 mg/L, while the n-hexane extract required 100 mg/L for effective inhibition. In conclusion, the findings indicate that the plant possesses significant antibacterial potential, warranting further research to isolate and characterize the specific phytoconstituents responsible for the observed antimicrobial activities.

Pubo Suburethral Suture Placement for Treatment of Stress Urinary Incontinence in a Woman with Mesh Exposure and Recurrent Incontinence

Objective: To present and assess the pubo suburethral suture placement (PSUSP) technique as a surgical treatment option for stress urinary incontinence (SUI) in patients with previous mesh exposure and recurrent incontinence. This technique aims to offer an alternative approach for patients where conventional methods may be contraindicated or have previously failed. The PSUSP procedure involves strategic suture placement to reinforce the pubovaginalis fascia, potentially enhancing structural support and functional outcomes. Case: A 56-year-old woman who had undergone transobturator tape (TOT) surgery 3 years prior presented with SUI. Clinical examination revealed persistent SUI and suburethral mesh exposure. Under spinal anesthesia, partial dissection and removal of the exposed mesh were performed. The vaginal mucosa was dissected from the pubocervical fascia to the pubic bone bilaterally. A zero polyester suture was passed through the retropubic fibrous tissue and the pubovaginalis fascia parallel to the urethra on the left side, and the procedure was mirrored on the right side. Twenty days postoperatively, the patient reported mixed urinary incontinence, and examination revealed local incisional dehiscence, suture detachment, and persistent SUI. A reoperation was conducted using a vertical incision. The vaginal mucosa was re-dissected from the pubocervical fascia, and PSUSP was re-implemented as previously described. The pubovaginalis fascia was repaired before the PSUSP sutures were secured. Postoperative evaluation indicated the resolution of mixed incontinence, with no further complications reported. Conclusion: This case illustrates that PSUSP can be a viable surgical technique for treating SUI in patients with a history of mesh exposure and recurrent incontinence. The reoperation success suggests that PSUSP may provide enhanced support to the pubovaginalis fascia, but further clinical studies are necessary to evaluate its long-term efficacy and safety profile.

Formulation and Ex Vivo Evaluation of Ivermectin Within Different Nano-Drug Delivery Vehicles for Transdermal Drug Delivery.

Background/Objectives: Ivermectin gained widespread attention as the "miracle drug" during the coronavirus disease 2019 (COVID-19) pandemic. Its inclusion in the 21st World Health Organization (WHO) List of Essential Medicines is attributed to its targeted anti-helminthic response, high efficacy, cost-effectiveness and favorable safety profile. Since the late 2000s, this bio-inspired active pharmaceutical ingredient (API) gained renewed interest for its diverse therapeutic capabilities. However, producing ivermectin formulations does remain challenging due to its poor water solubility, resulting in low bioavailability after oral administration. Therefore, the transdermal drug delivery of ivermectin was considered to overcome these challenges, which are observed after oral administration. Methods: Ivermectin was incorporated in a nano-emulsion, nano-emulgel and a colloidal suspension as ivermectin-loaded nanoparticles. The nano-drug delivery vehicles were optimized, characterized and evaluated through in vitro membrane release studies, ex vivo skin diffusion studies and tape-stripping to determine whether ivermectin was successfully released from its vehicle and delivered transdermally and/or topically throughout the skin. This study concluded with cytotoxicity tests using the methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on both human immortalized epidermal keratinocytes (HaCaT) and human immortalized dermal fibroblasts (BJ-5ta). Results: Ivermectin was successfully released from each vehicle, delivered transdermally and topically throughout the skin and demonstrated little to no cytotoxicity at concentrations that diffused through the skin. Conclusions: The type of nano-drug delivery vehicle used to incorporate ivermectin influences its delivery both topically and transdermally, highlighting the dynamic equilibrium between the vehicle, the API and the skin.

Phage therapeutic delivery methods and clinical trials for combating clinically relevant pathogens.

The ongoing global health crisis caused by multidrug-resistant (MDR) bacteria necessitates quick interventions to introduce new management strategies for MDR-associated infections and antimicrobial agents' resistance. Phage therapy emerges as an antibiotic substitute for its high specificity, efficacy, and safety profiles in treating MDR-associated infections. Various in vitro and in vivo studies denoted their eminent bactericidal and anti-biofilm potential. This review addresses the latest developments in phage therapy regarding their attack strategies, formulations, and administration routes. It additionally discusses and elaborates on the status of phage therapy undergoing clinical trials, and the challenges encountered in their usage, and explores prospects in phage therapy research and application.

Optimizing therapeutics: A novel mutual prodrug of ketoprofen and Chlorzoxazone for enhanced efficacy and safety

The development of mutual prodrugs signifies a pivotal advancement in the optimization of therapeutic profiles for established pharmaceuticals. This study explores the synthesis and evaluation of an innovative mutual prodrug combining the nonsteroidal anti-inflammatory drug (NSAID) Ketoprofen and the skeletal muscle relaxant Chlorzoxazone. Designed to alleviate gastric irritation inherent to NSAIDs while capitalizing on the synergistic benefits of both agents, the synthesized mutual prodrug was characterized and confirmed through extensive physicochemical and spectroscopic studies. Solubility and partition coefficient analyses indicated heightened lipophilicity, enhancing the prodrug's suitability for oral administration compared to its parent drugs. Additionally, protein binding studies revealed a low binding affinity, suggesting improved bioavailability. Subsequent in vitro hydrolysis studies assessed the prodrug's stability across various pH levels (1.2, 3, 5 and 7.4) simulated gastric and intestinal fluids, plasma and rat liver homogenate, with quantitative evaluation performed by high-performance liquid chromatography. The prodrug remained stable and unhydrolyzed in the stomach after absorption, but underwent rapid cleavage by esterase's in blood and rat liver homogenate, releasing the active parent drugs. Our investigation underscores the transformative potential of mutual prodrug design in optimizing the efficacy and safety profile of combining NSAIDs with muscle relaxants. This approach offers a novel therapeutic strategy that enhances patient outcomes while minimizing adverse effects, paving the way for innovative treatments in managing musculoskeletal conditions and improving overall quality of life.