Search Results (312)

This study focused on the poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer, which was recently reported as a novel material for polymeric nanoparticles to replace poly(DL-lactide-co-glycolide) (PLGA) as a drug carrier for prednisolone (PSL), and aimed to evaluate the efficacy of PSL-loaded PLGA-PEG-PLGA nanoparticles (NPs) against allergic contact dermatitis (ACD). PSL-loaded PLGA-PEG-PLGA NPs were prepared using the nanoprecipitation method, and their particle size distribution and mean particle size were measured using dynamic light scattering. 1-Fluoro-2,4-dinitrobenzene (DNFB) was used to create a mouse model of contact hypersensitivity (CHS). PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization with DNFB, and the therapeutic effect was evaluated by quantifying intracutaneous TNF-α and IL-4 levels suing ELISA. When PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization, TNF-α expression and IL-4 statements were significantly lower in the PSL-loaded PLGA-PEG-PLGA NP group than in the non-treated group. No significant difference was observed between the PSL-loaded PLGA-PEG-PLGA NP and PSL-loaded ointment groups, even though the steroid dose was 40 times lower than in the PSL-containing ointment. These results suggest that PSL-loaded PLGA-PEG-PLGA NPs may have a better effect in the treatment of ACD than PSL-loaded PLGA NPs. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Background/Objectives: The combination drug sulfamethoxazole/trimethoprim (ST) is a broad-spectrum antibiotic used against various infections; however, it is associated with several serious adverse events. The ST package inserts contain warnings about these adverse events. However, warnings vary internationally, and specific measures to address ST-related adverse events are unclear. Therefore, we aimed to comprehensively evaluate ST-related adverse events using the Japanese Adverse Drug Event Report (JADER) database and analyze the onset time for each event. Methods: Adverse events due to ST were analyzed using the JADER database between April 2004 and June 2023. The reported odds ratio and 95% confidence interval (95% confidence interval [CI]) were calculated, with a signal detected if the 95% CI lower limit exceeded 1. The Weibull distribution was used to characterize the onset time of adverse events with detected signals. Results: The total number of cases in the JADER database during the study period was 862,952, and the number of adverse events involving ST as a suspected drug was 4203. Adverse events associated with ST include hyperkalemia, syndrome of inappropriate antidiuretic hormone secretion, hematopoietic cytopenia, acute renal failure, hypoglycemia, disseminated intravascular coagulation syndrome, hepatic disorder, and the Stevens–Johnson syndrome/toxic epidermal necrolysis. Conclusions: Weibull analysis indicated an early failure-type onset time for all adverse events, suggesting the need for intensive adverse event monitoring of ST, especially in the first month of use. These findings may support revising drug package inserts in Japan to better reflect the identified risks. Full article

Background and Objectives: Conventional methods for removing cemented fixed prosthetic restorations (FPRs) are unreliable and lead to unsatisfactory outcomes. At their best, they allow the tooth to be saved at the expense of a laborious process that also wears down rotating tools and handpieces and occasionally results in abutment fractures. Restorations are nearly never reusable in any of these situations. Erbium-doped yttrium-aluminum-garnet (Er:YAG) and erbium-chromium yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers casafely and effectively remove FPRs, according to scientific studiesre. This study sets out to examine the impact of Er:YAG laser radiation on the debonding of different ceramic restorations, comparing the behavior of various ceramic prosthetic restoration types under laser radiation action and evaluating the integrity of prosthetic restorations and dental surfaces exposed to laser radiation. Materials and Methods: The study included a total of 16 removed teeth, each prepared on opposite surfaces as abutments.y. Based on the previously defined groups, four types of ceramic restorations were included in the study: feldspathic (F), lithium disilicates (LD), layered zirconia (LZ), and monolithic zirconia (MZ). The thickness of the prosthetic restorations was measured at three points, and two different materials were used for cementation. The Er:YAG Fotona StarWalker MaQX laser was used to debond the ceramic FPR at a distance of 10 mm using an R14 sapphire tip with 275 mJ, 20 Hz, 5.5 W, with air cooling (setting 1 of 9) and water. After debonding, the debonded surface was visualized under electron microscopy. Results: A total of 23 ceramic FPRs were debonded, of which 12 were intact and the others fractured into two or three pieces. The electron microscopy images showed that debonding took place without causing any harm to the tooth structure. The various restoration types had the following success rates: 100% for the LZ and F groups, 87% for the LD group, and 0% for the MZ group. In terms of cement type, debonding ceramic FPRs cemented with RELYX was successful 75% of the time, compared to Variolink DC’s 69% success rate. Conclusions: In summary, the majority of ceramic prosthetic restorations can be successfully and conservatively debonded with Er:YAG radiation. Full article

Caffeic acid (CA) is a naturally occurring polyphenol antioxidant found in coffee, tea, fruits, and vegetables, known for its strong antioxidant, anti-inflammatory, and anti-aging properties. However, its cosmetic application is limited because of poor dermal absorption due to its high polarity. This study aimed to evaluate the antioxidant and skin-brightening effects of a novel lipophilic CA derivative, CAD (caffeic acid-3,4-dihydroxyphenylpropanolester). CAD was synthesized by conjugating CA with 3,4-DHPEA, a lipophilic antioxidant derived from olive oil. In both DPPH and ABTS assays, CAD exhibited more potent antioxidant activity than CA. In B16F10 melanoma cells, CAD significantly inhibited melanin production without cytotoxicity at concentrations lower than those required for CA. Cellular assays using DCF-DA staining demonstrated that CAD effectively reduced intracellular ROS levels. Mechanistic studies revealed that CAD inhibited tyrosinase activity and downregulated the expression of TYR, TRP-1, and TRP-2. Additionally, CAD suppressed MITF phosphorylation, along with reduced phosphorylation of ERK and JNK, elucidating its anti-melanogenic mechanism. Importantly, CAD showed dose-dependent skin-brightening effects in the 3D human skin model Melanoderm™, as evidenced by increased lightness and histological evaluation. In conclusion, CAD demonstrates strong potential as a safe and effective antioxidant and skin-brightening agent for cosmetic applications. Full article

Photosafety assessments are a key requirement for the safe development of pharmaceuticals, cosmetics, and agrochemicals. Although in vitro methods are widely used for phototoxicity and photoallergy testing, their limited applicability and predictive power often necessitate supplemental in vivo studies. To address this, we developed the PhotoChem Reference Chemical Database, comprising 251 reference compounds with curated data from in vitro, in vivo, and human studies. Using this database, we evaluated the predictive capacity of three OECD in vitro test guidelines—TG 432 (3T3 NRU), TG 495 (ROS assay), and TG 498 (reconstructed human epidermis)—by comparing the results against human and animal data. Against human reference data, all three test methods showed high sensitivity (≥82.6%) and strong overall accuracy: TG 432 (accuracy: 94.2% (49/52)), TG 495 (100% (27/27)), and TG 498 (86.7% (26/30)). In comparison with animal data, sensitivity remained high for all tests (≥92.0%), while specificity varied: TG 432 (54.3% (19/35)), TG 495 (63.6% (7/11)), and TG 498 (90.5% (19/21)). TG 498 demonstrated the most balanced performance in both sensitivity and specificity across datasets. We also analyzed 106 drug approvals from major regulatory agencies to assess real-world application of photosafety testing. Since the mid-2000s, the use of in vitro phototoxicity assays has steadily increased in Korea, particularly following the 2021 revision of the MFDS regulations. Test method preferences varied by region, with 3T3 NRU and ROS assays most widely used to evaluate phototoxicity, while photo-LLNA and guinea pig tests were frequently employed for photoallergy assay. Collectively, this study provides a valuable reference for optimizing test method selection and supports the broader adoption of validated, human-relevant non-animal photosafety assessment strategies. Full article

Althaea rosea flower extract (ARFE) is widely used as a food and cosmetic ingredient. However, the systemic safety of ARFE for use in cosmetics has not been confirmed, yet. Here, we adopted the threshold of toxicological concern (TTC) and history of safe food consumption approaches to evaluate the systemic safety of ARFE as a cosmetic ingredient. A systematic literature review identified 48 chemical constituents in ARFE, 92.6% of which are common food components. Through a literature review, 48 chemical constituents of ARFE were identified. To exclude the potential genotoxicity issues, in silico predictions of an in vitro AMES test and additional literature reviews were performed, demonstrating that all the chemical constituents of ARFE have no genotoxicity issues. To evaluate the systemic toxicity of ARFE, a comparison with the dietary intake of ARFE was performed. The daily dietary intake of ARFE through tea products was estimated to be 66.67 mg/kg/day. Since exposure to ARFE through cosmetic use ranges from 0.0045 to 5.380 mg/kg/day, which is far lower than dietary intake, it is unlikely to pose any additional health risk. The TTC approach along with in silico predictions of dermal absorption also revealed that systemic exposure doses (SEDs) of all the chemical constituents are below TTC thresholds, further supporting its systemic safety for use in cosmetics. Full article

Objectives: Ritodrine, a tocolytic agent used to delay preterm labor, can cause several cardiovascular-associated adverse events (AEs). This study aimed to examine the relationship between gene polymorphisms in peroxisome proliferator-activated receptor gamma (PPARG) and PPARG coactivator-1α (PPARGC1A) and the occurrence of ritodrine-induced AEs. Additionally, a risk-scoring system was developed to identify patients at high risk of AEs. Methods: Patients aged 18 years or older who were administered ritodrine to manage preterm labor with intact membranes and uterine contractions occurring at 20–36 weeks of gestation were enrolled in this study. A total of 70 common PPARG and PPARGC1A variants (minor allele frequency ≥ 0.2) with low linkage disequilibrium (r² < 0.8) were selected from an Axiom™ Precision Medicine Research Array (AMPRA). Results: A total of 149 patients were included in the analysis. After adjusting for confounders (age, gestational age, and the maximum infusion rate), weight and rs2946385, rs35523565, and rs2240748 of PPARGC1A were identified as significant predictors associated with ritodrine-induced AEs. Based on the risk-scoring system, the predicted probabilities of AEs for patients with scores of 0, 1, 2, 3, 4, and 5 points were 4%, 9%, 18%, 35%, 55%, and 74%, respectively. The AUROC for the risk score predicting ritodrine-induced AEs was 0.729 (95% CI: 0.672–0.831, p < 0.001). Conclusions: This study indicates that ritodrine-induced AEs are related to PPARGC1A polymorphisms. A risk-scoring system based on genetic variants showed moderate predictive ability for ritodrine-induced AEs, suggesting potential utility in females with preterm labor. Full article

Background/Objectives: Voriconazole (VRCZ) use requires accurate monitoring to avoid suboptimal drug levels and adverse effects. In addition, the appearance of resistant fungal strains is a problem that needs attention. Blood concentration measurement is the monitoring technique of choice; however, it is slow, limiting its clinical application. This study aimed to evaluate the clinical utility of rapid therapeutic drug monitoring (TDM) for VRCZ using high-performance liquid chromatography with ultraviolet detection (HPLC-UV) compared to conventional outsourced liquid chromatography–tandem mass spectrometry (LC-MS/MS) testing in outpatient care. Methods: VRCZ blood concentrations were measured using HPLC-UV and LC-MS/MS. Reporting times, accuracy, and clinical outcomes were assessed for outpatients receiving VRCZ treatment. Safety was monitored for renal, hepatic, and visual toxicities. Results: HPLC-UV significantly reduced reporting times (0.433 h vs. 74.3 h, p < 0.001), and Deming’s regression analyses showed a strong correlation with LC-MS/MS results (Pearson’s r = 0.988). Bland–Altman analysis showed an average difference of 0.025 μg/mL between HPLC-UV and LC-MS/MS. Prospective monitoring of three outpatients revealed no adverse events, enabling safe and effective VRCZ dosing. Conclusions: Rapid VRCZ TDM using HPLC-UV is a cost-effective and feasible approach for outpatient care, significantly improving reporting times and patient safety. Further studies and cross-facility collaboration are needed to expand its application. Full article

To combine didactic education with clinical and research experiences that would empower student pharmacists to consider postgraduate training and a career in pharmacy education or academics, in 2009, the Next Generation of Pharmacist Educators (NextGenRxEd) program, a four-year longitudinal education program, was implemented at the University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences. Directed by two pharmacist faculty, a clinician and researcher, student pharmacists were exposed to hands-on experience with clinical management, patient care, and research processes. A post-graduation survey was created and administered in Fall 2024 to evaluate outcomes for all student pharmacists who completed the program. Key performance indicators included the number of pharmacy students proceeding to postgraduate training, research practices, and pharmacist positions involving education and academics. During 2009–2024, 34 student pharmacists completed the NextGenRxEd program; 71% achieved postgraduate education (22 PGY1 residencies and two fellowships). Following quality improvement implementation, this percentage increased from 50% to 89%, for Classes 2009–2015 and 2016–2024, respectively. Overall, the PGY1 match rate was 92%, and 19 abstracts/posters and 10 manuscripts were published, respectively. The post-graduation survey response rate was 85%, with 93% of respondents reporting that they precepted PharmD students; 14% became faculty members, and 66% participated in research. The NextGenRxEd program provides a model whereby student pharmacists are equipped to obtain post-graduate education and pursue a career with a significant role in pharmacy education or academic pharmacy. This program has the potential to be implemented at other pharmacy schools/colleges to benefit faculty and student participants. Full article

As medical devices become integral to modern healthcare, it is essential to prepare future pharmacists to counsel patients on device use and emerging therapeutic technologies. This study evaluates the impact of hands-on medical device training on pharmacy students at the University of Southern California (USC) Mann School of Pharmacy and Pharmaceutical Sciences, focusing on the level of comfort in counseling patients and retention of device-related information. Utilizing an active learning framework, this study provides insights into how experiential learning methods using medical devices enhance pharmacy students’ readiness for clinical practice. The results demonstrated significant improvement in levels of student comfort with counseling and information retention. The implementation of a hands-on training module has the potential to be adapted and applied to other courses or programs. The findings highlight the importance of integrating practical training within the pharmacy curriculum to better prepare graduates for effective patient education and support. Full article

Background and Aim: Biliary atresia is a rare, progressive disease that affects the bile ducts in newborns. Persistent bile duct obstruction induces various pathological conditions, including jaundice, inflammation, and liver fibrosis; however, the exact pathogenesis of biliary atresia is not yet fully understood. Nuclear factor-κB (NF-κB) is widely acknowledged as a key regulator in the pathogenesis of hepatitis and liver fibrosis, and extensive research has been conducted to develop strategies to effectively inhibit its activity to mitigate liver damage. Exosome-based therapeutic platforms offer targeted NF-κB inhibition with low immunogenicity and enhanced liver-specific delivery. This study aimed to evaluate the therapeutic efficacy of Exo-SrIκB in treating cholestatic liver fibrosis using experimental animal models. Methods: Exo-SrIκB (an exosome-based therapy containing the super-repressor IκB protein) using EXPLOR technology (Exosome engineering for Protein Loading via Optically Reversible protein-protein interactions) to encapsulate the super repressor IκB (SrIκB) within exosomes. The therapeutic efficacy of Exo-SrIκB was assessed in minipig and mouse models with experimentally induced cholestatic liver disease. Results: Administration of Exo-SrIκB significantly attenuated liver fibrosis progression in both animal models by inhibiting NF-κB nuclear translocation and reducing the expression of fibrotic markers. Treated animals exhibited reduced collagen deposition, lower α-SMA levels, and improved hepatic function compared to untreated controls. Conclusion: Exo-SrIκB effectively suppressed NF-κB signaling and alleviated liver fibrosis in experimental cholestatic liver disease models, suggesting that exosome-based therapeutics may offer a targeted and biocompatible application to managing liver fibrosis and other chronic liver diseases. Full article

Background: In 2015, the Directorate General of Drug Administration (DGDA) of Bangladesh accredited model pharmacies (MPs) to enhance the quality of pharmacy services across the country. We examined the challenges and opportunities for pharmacists in MPs, and also explored the perspectives of the pharmacy stakeholders for improving good pharmacy practices (GPPs) in Bangladesh. Methods: In-depth interviews (IDIs) were conducted with graduate pharmacists (Grade A) and diploma pharmacists (Grade B) recruited from a few selected MPs that were included in a previous study. Key informant interviews (KIIs) were conducted with the government and non-government stakeholders who were involved in pharmacy regulations and practices. Trained qualitative researchers conducted IDIs and KIIs using interview topic guides under relevant themes developed by the study investigators. Results: Between February and March 2021, nine Grade A and six Grade B pharmacists and nine government and non-government stakeholders were interviewed. The key challenges, as well as demotivational factors, for Grade A pharmacists were reported to be multiple responsibilities, inadequate salary, poor social status, an unfavorable working environment, long working hours, a lack of recognition, and low respect for their profession. However, Grade B pharmacists expressed job satisfaction, primarily due to working opportunities in reputable pharmacies and learning opportunities. The stakeholders reported a high operation cost of the MPs, a shortage of trained pharmacists, poor salary structures, and a lack of public awareness about the critical roles of the pharmacists in healthcare to be challenges of retaining Grade A pharmacists at the MPs. Addressing the challenges of the pharmacists and revising compensation packages along with strengthening monitoring systems would be important for improving GPPs at the MPs. Conclusions: This study has demonstrated that specifying the roles of the pharmacists, offering competitive packages, conducive working hours, and professional recognition would be imperative for the retention of trained pharmacists at MPs. Implementing regulatory standards and monitoring performance would enhance good pharmacy practices in Bangladesh. Full article

Background/Objectives: Earlier detection of severe immune-related hematological adverse events (irHAEs) in cancer patients treated with a PD-1 or PD-L1 inhibitor is critical to improving treatment outcomes. The study aimed to develop a simple machine learning (ML) model for predicting irHAEs associated with PD-1/PD-L1 inhibitors. Methods: We utilized the Observational Medical Outcomes Partnership–Common Data Model based on electronic medical records from a tertiary (KHMC) and a secondary (KHNMC) hospital in South Korea. Severe irHAEs were defined as Grades 3–5 by the Common Terminology Criteria for Adverse Events (version 5.0). The predictive model was developed using the KHMC dataset, and then cross-validated against an independent cohort (KHNMC). The full ML models were then simplified by selecting critical features based on the feature importance values (FIVs). Results: Overall, 397 and 255 patients were included in the primary (KHMC) and cross-validation (KHNMC) cohort, respectively. Among the tested ML algorithms, random forest achieved the highest accuracy (area under the receiver operating characteristic curve [AUROC] 0.88 for both cohorts). Parsimonious models reduced to 50% FIVs of the full models showed comparable performance to the full models (AUROC 0.83–0.86, p > 0.05). The KHMC and KHNMC parsimonious models shared common predictive features including furosemide, oxygen gas, piperacillin/tazobactam, and acetylcysteine. Conclusions: Considering the simplicity and adequate predictive performance, our simplified ML models might be easily implemented in clinical practice with broad applicability. Our model might enhance early diagnostic screening of irHAEs induced by PD-1/PD-L1 inhibitors, contributing to minimizing the risk of severe irHAEs and improving the effectiveness of cancer immunotherapy. Full article