Pharmaceutics最新文献

{"title":"Anti-Tumor Strategies of Photothermal Therapy Combined with Other Therapies Using Nanoplatforms.","authors":"Rubing Xu, Shengmei Wang, Qiuyan Guo, Ruqian Zhong, Xi Chen, Xinhua Xia","doi":"10.3390/pharmaceutics17030306","DOIUrl":"10.3390/pharmaceutics17030306","url":null,"abstract":"<p><p>Conventional cancer treatments often have complications and serious side effects, with limited improvements in 5-year survival and quality of life. Photothermal therapy (PTT) employs materials that convert light to heat when exposed to near-infrared light to raise the temperature of the tumor site to directly ablate tumor cells, induce immunogenic cell death, and improve the tumor microenvironment. This therapy has several benefits, including minimal invasiveness, high efficacy, reduced side effects, and robust targeting capabilities. Beyond just photothermal conversion materials, nanoplatforms significantly contribute to PTT by supplying effective photothermal conversion materials and bolstering tumor targeting to amplify anti-tumor effects. However, the anti-tumor effects of PTT alone are ultimately limited and often need to be combined with other therapies. This narrative review describes the recent progress of PTT combined with chemotherapy, radiotherapy, photodynamic therapy, immunotherapy, gene therapy, gas therapy, chemodynamic therapy, photoacoustic imaging, starvation therapy, and multimodal therapy. Studies have shown that combining PTT with other treatments can improve efficacy, reduce side effects, and overcome drug resistance. Despite the encouraging results, challenges such as optimizing treatment protocols, addressing tumor heterogeneity, and overcoming biological barriers remain. This paper highlights the potential for personalized, multimodal approaches to improve cancer treatment outcomes.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Nanoparticle Carriers of the Proapoptotic Protein Cytochrome <i>c</i>.","authors":"Alexandar M Zhivkov, Svetlana H Hristova, Trifon T Popov","doi":"10.3390/pharmaceutics17030305","DOIUrl":"10.3390/pharmaceutics17030305","url":null,"abstract":"<p><p>This review discusses the literature data on the synthesis, physicochemical properties, and cytotoxicity of composite nanoparticles bearing the mitochondrial protein cytochrome <i>c</i> (cytC), which can act as a proapoptotic mediator in addition to its main function as an electron carrier in the electron transport chain. The introduction of exogenous cytC via absorption of carrier particles, the phagocytosis of colloid particles of submicrometric size, or the receptor-mediated endocytosis of nanoparticles in cancer cells, initiates the process of apoptosis-a multistage cascade of biochemical reactions leading to complete destruction of the cells. CytC-carrier composite particles have the potential for use in the treatment of neoplasms with superficial localization: skin, mouth, stomach, colon, etc. This approach can solve the two main problems of anticancer therapy: selectivity and non-toxicity. Selectivity is based on the incapability of the normal cell to absorb (nano)particles, except for the cells of the immune system. The use of cytC as a protein that normally functions in mitochondria is harmless for the macroorganism. In this review, the factors limiting cytotoxicity and the ways to increase it are discussed from the point of view of the physicochemical properties of the cytC-carrier particles. The different techniques used for the preparation of cytC-bearing colloids and nanoparticles are discussed. Articles reporting the achievement of high cytotoxicity with each of the techniques are critically analyzed.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Different Cationic Polymer-Based Micelles on the Corneal Behavior and Anti-Cataract Effect of Diosmetin.","authors":"Jing Zhang, Min Zha, Anping Wan, Satya Siva Kishan Yalamarty, Nina Filipczak, Xiang Li","doi":"10.3390/pharmaceutics17030302","DOIUrl":"10.3390/pharmaceutics17030302","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background&lt;/b&gt; Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers-distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and (2,3-dioleoyloxypropyl) trimethylammonium chloride (DOTAP)-on the corneal behaviors and anti-cataract efficacy of diosmetin (DIO)-loaded micelles (D-M-P, D-M-T, and D-M-D, respectively). &lt;b&gt;Methods&lt;/b&gt; The DIO-loaded micelles were prepared using the thin-film dispersion method and incorporated with the three polymers through hydrophobic interactions and electrostatic adsorption. Structural characterization was demonstrated by TEM imaging and particle size analyzer. In vitro release behavior was detected by the dialysis method. Cell viability of D-M-P, D-M-T, and D-M-D on L929 cells was detected by CCK-8 assays, with cellular uptake performed using coumarin 6 as the fluorescence indicator. Precorneal retention behaviors of these three vesicles were observed by In Vivo Imaging System. Transcorneal permeability was determined by modified Franz diffusion method and the permeation routes of the vesicles are investigated. Selenite-induced cataract model was established. The anti-cataract effects of three different DIO-loaded micelles were evaluated by the observation of lens opacity and antioxidant enzyme activities. Eye Irritation of the DIO in different preparations was estimated using the Draize test, along with H&E staining of the corneas. &lt;b&gt;Results&lt;/b&gt; Structural characterization of DIO-loaded micelles revealed that the vesicles were spherical, with a uniform size distribution of around 28 nm, a similar surface potential of approximately 6.0 mV, and a high DIO entrapment efficiency of about 95%. Compared to the DIO suspension, all three formulations exhibited a significant sustained-release effect. They showed no signs of irritation and demonstrated increased IC50 values in L929 cells, indicating improved biocompatibility. Cellular uptake in human lens epithelial cells (HLECs) was assessed using confocal laser scanning microscopy. C-M-T displayed the highest fluorescence signals, with a cellular internalization 3.2 times greater than that of the solution group. Both C-M-T and C-M-P enhanced vesicle retention on the corneal surface by at least 47.8% compared to the Cou-6 solution. Furthermore, TMC facilitated the paracellular transport of vesicles into the deepest layers of the cornea and delivered DIO across the cornea, with a &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;app&lt;/sub&gt; value 3.11 times and 1.49 times those of D-M-D and D-M-P, respectively. In terms of therapeutic efficacy, D-M-T demonstrated the most significant attenuation of lens opacity, along with enhanced antioxidant enzyme activities and inhibition of lipid peroxidation. &lt;b&gt;Conclusion&lt;/b&gt; The modificati","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Microemulsions: Influence of Compositions on the Dermal Penetration Efficacy.","authors":"Muzn Alkhaldi, Soma Sengupta, Cornelia M Keck","doi":"10.3390/pharmaceutics17030301","DOIUrl":"10.3390/pharmaceutics17030301","url":null,"abstract":"<p><p><b>Background/Objective</b>: This study provided a comparison of the influence of each component of the microemulsion formulation and investigated the impact of varying concentrations of the microemulsion components on curcumin's ability to penetrate the skin using an ex vivo porcine ear model. <b>Methods</b>: Curcumin microemulsions with different compositions were prepared and analyzed for their physicochemical properties. The dermal penetration efficacy of curcumin was evaluated from the different formulations and compared with non-microemulsion formulations. <b>Results</b>: Findings proved that microemulsion formulations improve the dermal penetration efficacy for curcumin when compared with non-microemulsion formulations. The composition of the microemulsion affects the penetration efficacy of curcumin and increases with decreasing oil content and increasing surfactant and water content. The best penetration for curcumin is achieved with a microemulsion that contained 7.7 g of medium-chain triglycerides as the oil phase, 6.92 g of Tween^® 80 and 62.28 g of ethanol as the surfactant mixture, and 23.1 g water. <b>Conclusions</b>: The present study provides a foundational basis for further development of different microemulsion formulations for enhancing the dermal penetration of poorly water-soluble active compounds.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview on the Role of Ionic Liquids and Deep Eutectic Solvents in Oral Pharmaceuticals.","authors":"Stefano Sangiorgi, Beatrice Albertini, Serena Bertoni, Nadia Passerini","doi":"10.3390/pharmaceutics17030300","DOIUrl":"10.3390/pharmaceutics17030300","url":null,"abstract":"<p><p>Over the past twenty years, ionic liquids (ILs) and deep eutectic solvents (DESs) have gained recognition across various fields, including catalysis, extraction and purification, materials science, and biotechnology. Notably, the use of ILs and DESs in pharmaceutical research, especially in drug delivery, has seen remarkable expansion over the past decade. This review offers a comprehensive analysis of ILs and DESs specifically designed for the oral administration of drugs having unfavorable biopharmaceutical properties. The classification and characteristics of ILs and DESs, along with their newer natural (Bio-ILs and NaDESs) and therapeutic subcategories (API-ILs and TheDESs) are outlined. Additionally, a further subgroup of ILs, known as surface active ionic liquids (SAILs), is described. Then, a detailed examination of the available manufacturing methods in a sustainable, time-consuming, and scalable perspective, and toxicity concerns in relation to their subdivision are evaluated. Finally, their specific applications in oral drug delivery, whether used as neat solvents or converted into administrable dosage forms, are analyzed and discussed. Despite the significant advancements in recent years regarding the use of these solvents in oral drug delivery, there are still many aspects that need further investigation. These include their interaction with biological systems (gastrointestinal fluids and mucosa), their long-term stability, and the development of effective drug delivery systems.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Quantitative Approach to Potency Testing for Chimeric Antigen Receptor-Encoding Lentiviral Vectors and Autologous CAR-T Cell Products, Using Flow Cytometry.","authors":"Juan José Mata-Molanes, Leticia Alserawan, Carolina España, Carla Guijarro, Ana López-Pecino, Hugo Calderón, Ane Altuna, Lorena Pérez-Amill, Nela Klein-González, Carlos Fernández de Larrea, Europa Azucena González-Navarro, Julio Delgado, Manel Juan, Maria Castella","doi":"10.3390/pharmaceutics17030303","DOIUrl":"10.3390/pharmaceutics17030303","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Potency testing of clinical-grade lentiviral vectors (LVVs) is critical to support a drug's commercial approval. Careful consideration should be paid to the development of a suitable potency test during the drug's clinical development. We aimed to develop an affordable, quantitative test for our CAR19-LVV, based on a measure of transgene's functional activity. <b>Methods</b>: Several indicators of functional activity of CAR19-LVV were explored in a co-culture setting of CAR-transduced Jurkat cells and CD19-expressing target cells. The selected assay was further developed and subjected to validation. Assay's adaptability to other CAR-encoding LVV and autologous CAR-T cell products was also investigated. <b>Results</b>: Measure of CD69 expression on the membrane of Jurkat-CAR-expressing cells is a specific indicator of CAR functionality. Quantification of CD69 in terms of mean fluorescence intensity (MFI), coupled with an intra-assay standard curve calibration, allows for a quantitative assay with high precision, specificity, robustness, linearity and accuracy. The assay has also shown optimal performance for a CARBCMA-LVV product. Importantly, we show that in primary T cells, CD69 expression reflects CAR-T cell cytotoxicity. After adaptation, we have applied a CD69-based potency test, with simultaneous measurement of CAR-T cell cytotoxicity, to autologous CAR-T cell products, demonstrating the assay's specificity also in this context. <b>Conclusions</b>: We developed a validated, in vitro cell-based potency test, using a quantitative flow-cytometry method, for our CAR19-LVV. The assay is based on the detection of T-cell activation upon CAR binding to antigen, which is a measure of transgene functionality. The assay was easily adapted to another CAR-encoding LVV, targeting a different molecule. Furthermore, the same assay principle can be applied in the context of autologous CAR-T cell products. The quantitative CD69 potency assay shows reduced variability among autologous products compared to the IFNγ assay and allows for simultaneous evaluation of traditional semi-quantitative cytotoxicity, thereby directly evaluating the drug's mechanism of action (MoA) in the same assay.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artesunate: A Review of Its Potential Therapeutic Effects and Mechanisms in Digestive Diseases.","authors":"Mengting Shi, Guanhua Ma, Xiulan Yang","doi":"10.3390/pharmaceutics17030299","DOIUrl":"10.3390/pharmaceutics17030299","url":null,"abstract":"<p><p>Artesunate (ART), an artemisinin-derived semi-synthetic sesquiterpene lactone distinguished by its unique endoperoxide group, has become a cornerstone of clinical antimalarial therapy. Recent research has demonstrated its broad pharmacological profile, including its potent antimalarial, anti-inflammatory, anti-tumor, antidiabetic, immunomodulatory, and anti-fibrotic properties. These discoveries have significantly broadened the therapeutic scope of ART and offer new perspectives for its potential use in treating gastrointestinal disorders. Mechanistically, ART exerts significant therapeutic effects against diverse gastrointestinal pathologies-such as gastric ulcers, ulcerative colitis (UC), hepatic fibrosis (HF), gastric cancer, hepatocellular carcinoma, and colorectal cancer-via multimodal mechanisms, including cell cycle modulation, apoptosis induction, the suppression of tumor cell invasion and migration, proliferation inhibition, ferroptosis activation, and immune regulation. This review evaluates existing evidence on ART's therapeutic applications and molecular mechanisms in digestive diseases, intending to elucidate its clinical translation potential. ART emerges as a promising multi-target agent with significant prospects for improving the management of gastrointestinal disorders.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Pharmacological Mechanisms of <i>Bombyx mori</i> (Abresham), a Traditional Arabic Unani Medicine for Ischemic Heart Disease: An Integrative Molecular Simulation Study.","authors":"Doni Dermawan, Nasser Alotaiq","doi":"10.3390/pharmaceutics17030295","DOIUrl":"10.3390/pharmaceutics17030295","url":null,"abstract":"<p><p><b>Background</b>: Ischemic heart disease (IHD), a leading cause of cardiovascular morbidity and mortality, continues to challenge modern medicine. <i>Bombyx mori</i> (Abresham), a traditional ingredient in Unani medicine, has shown promise in cardiovascular health, but its molecular mechanisms remain poorly understood. <b>Methods:</b> To explore the therapeutic potential of <i>Bombyx mori</i> for IHD, an integrative molecular simulation approach was applied. Network pharmacology was employed to identify the most favorable target receptor for the disease. Molecular docking simulations evaluated the binding affinities of chemical and protein-based compounds from <i>Bombyx mori</i> to the selected receptor. Molecular dynamics (MD) simulations confirmed the stability of these interactions under physiological conditions. Pharmacophore modeling identified key structural features critical for bioactivity, while in silico toxicity assessments evaluated the safety profiles of the compounds. <b>Results:</b> Key bioactive compounds from <i>Bombyx mori</i>, including Menaquinone-7, Quercetin, and Behenic acid, showed strong interactions with the target receptor, ACE2. The MD-based MM/PBSA calculations revealed the binding free energy values of Menaquinone-7 (-35.12 kcal/mol), Quercetin (-29.38 kcal/mol), and Behenic acid (-27.76 kcal/mol), confirming their strong binding affinity. Protein-based compounds, such as Chorion class high-cysteine HCB protein 13 (-212.43 kcal/mol), Bombyxin A-5 (-209.36 kcal/mol), and FMRFamide-related peptides (-198.93 kcal/mol), also displayed promising binding affinities. In silico toxicity assessments revealed favorable safety profiles for most compounds. <b>Conclusions:</b> This study positions <i>Bombyx mori</i> as a promising source of therapeutic agents for IHD. Future work should focus on experimental validation of these computational findings through in vitro and in vivo studies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silver Dimolybdate Nanorods: In Vitro Anticancer Activity Against Breast and Prostate Tumors and In Vivo Pharmacological Insights.","authors":"João Victor Barbosa Moura, Natália Cristina Gomes-da-Silva, Luciana Magalhães Rebêlo Alencar, Wellington Castro Ferreira, Cleânio da Luz Lima, Ralph Santos-Oliveira","doi":"10.3390/pharmaceutics17030298","DOIUrl":"10.3390/pharmaceutics17030298","url":null,"abstract":"<p><p><b>Background</b>: The development of nanostructured materials for cancer therapy has garnered significant interest due to their unique physicochemical properties, including enhanced surface area and tunable electronic structures, which can facilitate targeted drug delivery and oxidative stress modulation. This study investigates the anticancer potential of monoclinic silver dimolybdate nanorods (m-Ag₂Mo₂O₇) against aggressive breast (MDA-MB-231) and prostate (PC-3) cancer cells and explores their in vivo pharmacokinetic behavior. <b>Methods</b>: m-Ag₂Mo₂O₇ nanorods were synthesized via a hydrothermal method and characterized using XRD, SEM, Raman, and FTIR spectroscopy. In vitro cytotoxicity was evaluated using MTT assays on MDA-MB-231 and PC-3 cell lines across concentrations ranging from 1.56 to 100 µg/mL. In vivo biodistribution and radiopharmacokinetics were assessed using technetium-99m-labeled nanorods in male Swiss rats, with gamma counting employed for tissue uptake analysis and pharmacokinetic parameter determination. <b>Results</b>: m-Ag₂Mo₂O₇ nanorods exhibited a modest cytotoxic effect on MDA-MB-231 cells, with 50 µg/mL reducing cell viability by 23.5% (<i>p</i> < 0.05), while no significant cytotoxicity was observed in PC-3 cells. In vivo studies revealed predominant accumulation in the stomach, liver, spleen, and bladder, indicating reticuloendothelial system uptake and renal clearance. Pharmacokinetic analysis showed a rapid systemic clearance (half-life ~6.76 h) and a low volume of distribution (0.0786 L), suggesting primary retention in circulation with minimal off-target diffusion. <b>Conclusions</b>: While m-Ag₂Mo₂O₇ nanorods display limited standalone cytotoxicity, their ability to induce oxidative stress and favorable pharmacokinetic profile support their potential as adjuvant agents in cancer therapy, particularly for chemoresistant breast cancers. Further studies are warranted to elucidate their molecular mechanisms, optimize combinatorial treatment strategies, and assess long-term safety in preclinical models.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amikacin Dosing Adjustment in Critically Ill Oncologic Patients: A Study with Real-World Patients, PBPK Analysis, and Digital Twins.","authors":"Juliana Queiroz da Silva, Natália Valadares de Moraes, Rita Estrela, Diogenes Coelho, Diego Feriani, Karen Migotto, Pedro Caruso, Ivan Leonardo França E Silva, Daiane de Araujo Oliveira, João Paulo Telles, Fernanda de Lima Moreira","doi":"10.3390/pharmaceutics17030297","DOIUrl":"10.3390/pharmaceutics17030297","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Guidelines recommend adjusting amikacin dosing based on patients' renal function. Nevertheless, for critically ill cancer patients, the renal function equations based on serum creatinine levels have low or no correlation with amikacin clearance. Considering this, using real-world data, we built an amikacin PBPK model to predict amikacin plasma concentrations in critically ill oncologic patients stratified by renal impairment levels. Further, the model was applied for dose stratification and individualization (digital twin strategy) in this population. <b>Methods:</b> In the Therapeutic Drug Monitoring (TDM) study, 368 amikacin pharmacokinetic analyses from 184 critically ill cancer patients were enrolled in three cohorts. A full-body PBPK model was developed using PK-Sim v. 11.3. <b>Results:</b> The final PBPK model accounted for two groups of critically ill cancer patients with mild (creatinine clearance; CLcr ≥ 60 mL/min) or severe (CLcr < 60 mL/min) renal dysfunction. In the dose stratification strategy, at the 7th dose, cancer patients with CLcr ≥ 60 mL/min under regimens 20 mg/kg (q24h); 25 mg/kg (q24h); 25 mg/kg (q48h); and 30 mg/kg (q72h) have probability of ≥69% of the patients achieving the efficacy target (AUC/MIC > 80, MIC of 4 mg/L), while cancer patients with CLcr < 60 mL/min under regimens 7.5 mg/kg (q24h); 15 mg/kg (q24h); 15 mg/kg (q48h); and 20 mg/kg (q36h) have ≥90% probability of achieving the same efficacy target. <b>Conclusions:</b> Our MIPD approach demonstrates potential in optimizing amikacin dosing for critically ill cancer patients. However, it does not eliminate the need for TDM due to unexplained variability still not accounted for by the PBPK model.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}