Pharmaceutics最新文献_第3页

Lipid-Based Gels for Delivery of 3-O-Ethyl L-Ascorbic acid in Topical Applications 在局部应用中输送 3-O-乙基 L-抗坏血酸的脂基凝胶

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-07 DOI: 10.3390/pharmaceutics16091187

Noèlia Loza-Rodríguez, Aina Millán-Sánchez, Mireia Mallandrich, Ana Cristina Calpena, Olga López

{"title":"Lipid-Based Gels for Delivery of 3-O-Ethyl L-Ascorbic acid in Topical Applications","authors":"Noèlia Loza-Rodríguez, Aina Millán-Sánchez, Mireia Mallandrich, Ana Cristina Calpena, Olga López","doi":"10.3390/pharmaceutics16091187","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091187","url":null,"abstract":"This study explores the incorporation of 10% 3-O-ethyl L-ascorbic acid (ETVC), a derivative of vitamin C, into two lipid gel systems: a hydrogel (HG) consisting exclusively of lipids and water and a bigel (BG) combining the hydrogel with an oleogel made from olive oil and beeswax. We investigated the ETVC release profiles from both materials using synthetic membranes and measured their permeation through porcine skin in vitro. Additionally, the interaction of these lipid gel systems with the stratum corneum (SC) was determined. Results from the release study indicate that the BG exhibited slower ETVC release compared to the HG. The permeation experiments showed that the presence of lipids in the formulations enhanced ETVC retention in the skin. The HG delivered a higher amount to the SC, while the BG achieved greater retention in the epidermis. This difference is attributed to the different lipophilic nature of each material. The structural analysis of SC lipids revealed that the organization of surface lipids remained unaltered by the application of the gels. Finally, an in vitro efficacy test in porcine skin using methylene blue indicated that our ETVC gels exhibited antioxidant activity. These findings provide valuable insights into the potential of lipid-based gels for topical applications.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacometrics to Evaluate Dosing of the Patient-Friendly Ivermectin CHILD-IVITAB in Children ≥ 15 kg and <15 kg 采用药物计量学方法评估伊维菌素 CHILD-IVITAB 在体重≥ 15 千克和小于 15 千克儿童中的用药剂量

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-07 DOI: 10.3390/pharmaceutics16091186

Klervi Golhen, Michael Buettcher, Jörg Huwyler, John van den Anker, Verena Gotta, Kim Dao, Laura E. Rothuizen, Kevin Kobylinski, Marc Pfister

{"title":"Pharmacometrics to Evaluate Dosing of the Patient-Friendly Ivermectin CHILD-IVITAB in Children ≥ 15 kg and <15 kg","authors":"Klervi Golhen, Michael Buettcher, Jörg Huwyler, John van den Anker, Verena Gotta, Kim Dao, Laura E. Rothuizen, Kevin Kobylinski, Marc Pfister","doi":"10.3390/pharmaceutics16091186","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091186","url":null,"abstract":"The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and (ii) to evaluate dosing for studies in children < 15 kg. Simulations were performed to identify dosing with CHILD-IVITAB associated with similar exposure coverage in children ≥ 15 kg and < 15 kg as observed in adults receiving the reference formulation STROMECTOL®. A total of 448 ivermectin concentrations were available from 16 healthy adults. The absorption rate constant was 2.41 h−1 (CV 19%) for CHILD-IVITAB vs. 1.56 h−1 (CV 43%) for STROMECTOL®. Simulations indicated that 250 µg/kg of CHILD-IVITAB is associated with exposure coverage in children < 15 kg consistent with that observed in children ≥ 15 kg and adults receiving 200 µg/kg of STROMECTOL®. Performed analysis confirmed that CHILD-IVITAB is associated with faster and more controlled absorption than STROMECTOL®. Simulations indicate that 250 µg/kg of CHILD-IVITAB achieves equivalent ivermectin exposure coverage in children < 15 kg as seen in children ≥ 15 kg and adults.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alternative Strategies for Delivering Immunotherapeutics Targeting the PD-1/PD-L1 Immune Checkpoint in Cancer 针对癌症中 PD-1/PD-L1 免疫检查点的免疫疗法的替代策略

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-07 DOI: 10.3390/pharmaceutics16091181

Ryunosuke Hoshi, Kristyna A. Gorospe, Hagar I. Labouta, Taha Azad, Warren L. Lee, Kelsie L. Thu

{"title":"Alternative Strategies for Delivering Immunotherapeutics Targeting the PD-1/PD-L1 Immune Checkpoint in Cancer","authors":"Ryunosuke Hoshi, Kristyna A. Gorospe, Hagar I. Labouta, Taha Azad, Warren L. Lee, Kelsie L. Thu","doi":"10.3390/pharmaceutics16091181","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091181","url":null,"abstract":"The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint constitutes an inhibitory pathway best known for its regulation of cluster of differentiation 8 (CD8)+ T cell-mediated immune responses. Engagement of PD-L1 with PD-1 expressed on CD8+ T cells activates downstream signaling pathways that culminate in T cell exhaustion and/or apoptosis. Physiologically, these immunosuppressive effects exist to prevent autoimmunity, but cancer cells exploit this pathway by overexpressing PD-L1 to facilitate immune escape. Intravenously (IV) administered immune checkpoint inhibitors (ICIs) that block the interaction between PD-1/PD-L1 have achieved great success in reversing T cell exhaustion and promoting tumor regression in various malignancies. However, these ICIs can cause immune-related adverse events (irAEs) due to off-tumor toxicities which limits their therapeutic potential. Therefore, considerable effort has been channeled into exploring alternative delivery strategies that enhance tumor-directed delivery of PD-1/PD-L1 ICIs and reduce irAEs. Here, we briefly describe PD-1/PD-L1-targeted cancer immunotherapy and associated irAEs. We then provide a detailed review of alternative delivery approaches, including locoregional (LDD)-, oncolytic virus (OV)-, nanoparticle (NP)-, and ultrasound and microbubble (USMB)-mediated delivery that are currently under investigation for enhancing tumor-specific delivery to minimize toxic off-tumor effects. We conclude with a commentary on key challenges associated with these delivery methods and potential strategies to mitigate them.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release 用于控制和持续释放药物的聚合物给药载体的最新进展

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-07 DOI: 10.3390/pharmaceutics16091184

Hong Lu, Zheng Cai, Ping Hu

引用次数: 0

Biologics in Systemic Lupus Erythematosus: Recent Evolutions and Benefits 系统性红斑狼疮的生物制剂：最新进展和益处

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-06 DOI: 10.3390/pharmaceutics16091176

Nilima Rajpal Kundnani, Mihaela Codrina Levai, Mihaela-Diana Popa, Claudia Borza, Mihai Iacob, Alexandra Laura Mederle, Alexandru Blidisel

{"title":"Biologics in Systemic Lupus Erythematosus: Recent Evolutions and Benefits","authors":"Nilima Rajpal Kundnani, Mihaela Codrina Levai, Mihaela-Diana Popa, Claudia Borza, Mihai Iacob, Alexandra Laura Mederle, Alexandru Blidisel","doi":"10.3390/pharmaceutics16091176","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091176","url":null,"abstract":"Introduction: Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by significant autoantibodies, particularly targeting nuclear antigens. SLE pathogenesis involves genetic, environmental, and hormonal factors. The disease course includes flares and remission and involves various organs. Recent therapeutic progresses, including biologics, have improved management and prognosis, though the long-term impact of novel therapies remains to be determined. Biologics in SLE: Rituximab, the earliest B-cell-oriented biologic, binds CD20 and depletes CD20+ B cells, leading to remission in some SLE patients. Belimumab is a B-cell-activating factor (BAFF) inhibitor with a recent additional indication for lupus nephritis. The CALIBRATE and BLISS-BELIEVE studies investigated combinations of these drugs with conventional therapies, showing varied efficacy. Ocrelizumab and obinutuzumab, newer CD20-oriented SLE therapies, together with ofatumumab and veltuzumab, are also promising. The latest trials highlight their efficacy and safety. Anifrolumab, targeting type-I interferon receptors, was evaluated in the TULIP 1/2 trials. The ongoing TULIP LTE trial supports the long-term safety and efficacy of anifrolumab. Additionally, the IRIS Phase III trial is exploring anifrolumab for lupus nephritis, showing favorable renal responses. Tocilizumab and secukinumab are being assessed for SLE, with mixed outcomes. Several biologics targeting the C5 complement protein, together with immunomodulators and immunotherapeutics, are also under investigation for potential benefits in SLE. Discussion: Biologics in SLE target specific immune components, aiming to improve disease control and reduce the side effects of conventional therapy. However, trial outcomes vary due to factors like inclusion criteria and trial design. Conclusions: Biotechnology progress enables targeted biologic therapies for SLE, reducing disease activity and improving patients’ quality of life.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy 基于内源性 L-谷胱甘肽氧化分子制备具有谷胱甘肽响应性的紫杉醇原药，用于癌症治疗

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-06 DOI: 10.3390/pharmaceutics16091178

Xiao Duan, Qiang Wang, Yue Wang, Xinping Liu, Manman Lu, Zhifang Li, Xuelian Jiang, Jingquan Ji

{"title":"Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy","authors":"Xiao Duan, Qiang Wang, Yue Wang, Xinping Liu, Manman Lu, Zhifang Li, Xuelian Jiang, Jingquan Ji","doi":"10.3390/pharmaceutics16091178","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091178","url":null,"abstract":"Using an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis. The carboxyl groups in L-glutathione oxidized were reacted with the hydroxyl group in paclitaxel (PTX) using the catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Then, the amino-polyethylene glycol monomethyl ether (mPEG-NH2) was conjugated with GSSG to prepare PTX-GSSG-PEG. The structure of PTX-GSSG-PEG was characterized using infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). The drug release kinetics of PTX within PTX-GSSG-PEG were quantified using ultraviolet spectroscopy (UV-Vis). The size of the PTX-GSSG-PEG micelles was 83 nm, as evaluated using dynamic light scattering (DLS), and their particle size remained stable in a pH 7.4 PBS for 7 days. Moreover, the micelles could responsively degrade and release PTX in a reduced glutathione environment. The drug loading of PTX in PTX-GSSG-PEG was 13%, as determined using NMR. Furthermore, the cumulative drug release rate of PTX from the micelles reached 72.1% in a reduced glutathione environment of 5 mg/mL at 120 h. Cell viability experiments demonstrated that the PTX-GSSG-PEG micelles could induce the apoptosis of MCF-7 cells. Additionally, cell uptake showed that the micelles could distribute to the cell nuclei within 7 h. To sum up, with this glutathione-responsive paclitaxel prodrug micelle based on the endogenous molecule GSSG, it may be possible to develop novel nanomedicines in the future.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Direct and Abscopal Antitumor Responses Elicited by AlPcNE-Mediated Photodynamic Therapy in a Murine Melanoma Model 由 AlPcNE 介导的光动力疗法在小鼠黑色素瘤模型中引发的直接和缺席抗肿瘤反应

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-06 DOI: 10.3390/pharmaceutics16091177

José Athayde Vasconcelos Morais, Pedro H. A. Barros, Marcelo de Macedo Brigido, Clara Luna Marina, Anamelia Bocca, André de Lima e Silva Mariano, Paulo E. N. de Souza, Karen L. R. Paiva, Marina Mesquita Simões, Sonia Nair Bao, Luana C. Camargo, João P. Figueiró Longo, Amanda Alencar Cabral Morais, Ricardo B. de Azevedo, Marcio J. P. Fonseca, Luis A. Muehlmann

{"title":"Direct and Abscopal Antitumor Responses Elicited by AlPcNE-Mediated Photodynamic Therapy in a Murine Melanoma Model","authors":"José Athayde Vasconcelos Morais, Pedro H. A. Barros, Marcelo de Macedo Brigido, Clara Luna Marina, Anamelia Bocca, André de Lima e Silva Mariano, Paulo E. N. de Souza, Karen L. R. Paiva, Marina Mesquita Simões, Sonia Nair Bao, Luana C. Camargo, João P. Figueiró Longo, Amanda Alencar Cabral Morais, Ricardo B. de Azevedo, Marcio J. P. Fonseca, Luis A. Muehlmann","doi":"10.3390/pharmaceutics16091177","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091177","url":null,"abstract":"Melanoma, the most aggressive form of skin cancer, presents a major clinical challenge due to its tendency to metastasize and recalcitrance to traditional therapies. Despite advances in surgery, chemotherapy, and radiotherapy, the outlook for advanced melanoma remains bleak, reinforcing the urgent need for more effective treatments. Photodynamic therapy (PDT) has emerged as a promising alternative, leading to targeted tumor destruction with minimal harm to surrounding tissues. In this study, the direct and abscopal antitumor effects of PDT in a bilateral murine melanoma model were evaluated. Although only one of the two tumors was treated, effects were observed in both. Our findings revealed significant changes in systemic inflammation and alterations in CD4+ and CD8+ T cell populations in treated groups, as evidenced by blood analyses and flow cytometry. High-throughput RNA sequencing (RNA-Seq) further unveiled shifts in gene expression profiles in both treated and untreated tumors. This research sheds light on the novel antitumor and abscopal effects of nanoemulsion of aluminum chloride phthalocyanine (AlPcNE)-mediated PDT in melanoma, highlighting the potential of different PDT protocols to modulate immune responses and to achieve more effective and targeted cancer treatments.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anticipating Leucovorin Rescue Therapy in Patients with Osteosarcoma through Methotrexate Population Pharmacokinetic Model 通过甲氨蝶呤群体药代动力学模型预测骨肉瘤患者的亮菌甲素替代疗法

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-06 DOI: 10.3390/pharmaceutics16091180

Laura Ben Olivo, Pricilla de Oliveira Henz, Sophia Wermann, Bruna Bernar Dias, Gabriel Osorio Porto, Amanda Valle Pinhatti, Manoela Domingues Martins, Lauro José Gregianin, Teresa Dalla Costa, Bibiana Verlindo de Araújo

{"title":"Anticipating Leucovorin Rescue Therapy in Patients with Osteosarcoma through Methotrexate Population Pharmacokinetic Model","authors":"Laura Ben Olivo, Pricilla de Oliveira Henz, Sophia Wermann, Bruna Bernar Dias, Gabriel Osorio Porto, Amanda Valle Pinhatti, Manoela Domingues Martins, Lauro José Gregianin, Teresa Dalla Costa, Bibiana Verlindo de Araújo","doi":"10.3390/pharmaceutics16091180","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091180","url":null,"abstract":"Methotrexate (MTX), which presents high inter-individual variability, is part of the Brazilian Osteosarcoma Treatment Group (BOTG) protocol. This work aimed to develop a MTX population pharmacokinetic model (POPPK) for Brazilian children with osteosarcoma (OS) following the BOTG protocol to guide rescue therapy and avoid toxicity. The model was developed in NONMEM 7.4 (Icon®) using retrospective sparse data from MTX therapeutic drug monitoring of children attending a southern Brazilian public reference hospital. Data were described by a two-compartment model using 216 MTX cycles from 32 patients (5–18 y.o.) with OS who received 12 g/m2 dose/cycle. To explain inter-individual and inter-occasion variability in clearance and peripheral volume, covariates from demographic and biochemical data were evaluated. Serum creatinine was a significant covariate of MTX clearance (14.8 L/h), and the body surface area (BSA) was significant for central compartment volume (82.5 L). Inter-compartmental clearance and volume of peripheral compartment were 0.178 L/h and 5.72 L, respectively. The model adequately describes MTX exposure in Brazilian children with OS. Successful simulations were performed to predict MTX concentrations in pediatric patients above five years old with acute kidney injury and anticipate rescue therapy adjustments.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Auraptene Boosts the Efficacy of the Tamoxifen Metabolites Endoxifen and 4-OH-Tamoxifen in a Chemoresistant ER+ Breast Cancer Model 枳实能增强他莫昔芬代谢物恩多昔芬和 4-OH-他莫昔芬在化疗耐药 ER+ 乳腺癌模型中的疗效

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-06 DOI: 10.3390/pharmaceutics16091179

Angel Pulido-Capiz, Brenda Chimal-Vega, Luis Pablo Avila-Barrientos, Alondra Campos-Valenzuela, Raúl Díaz-Molina, Raquel Muñiz-Salazar, Octavio Galindo-Hernández, Victor García-González

{"title":"Auraptene Boosts the Efficacy of the Tamoxifen Metabolites Endoxifen and 4-OH-Tamoxifen in a Chemoresistant ER+ Breast Cancer Model","authors":"Angel Pulido-Capiz, Brenda Chimal-Vega, Luis Pablo Avila-Barrientos, Alondra Campos-Valenzuela, Raúl Díaz-Molina, Raquel Muñiz-Salazar, Octavio Galindo-Hernández, Victor García-González","doi":"10.3390/pharmaceutics16091179","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091179","url":null,"abstract":"Approximately 80% of breast cancer (BC) cases are estrogen receptor positive (ER+) and sensitive to hormone treatment; Tamoxifen is a prodrug, and its main plasmatic active metabolites are 4-hydroxytamoxifen (4-OH Tam) and endoxifen. Despite the effectiveness of tamoxifen therapy, resistance can be developed. An increment in eukaryotic initiation factor-4A complex (eIF4A) activity can result in tamoxifen-resistant tumor cells. For this work, we developed a cell variant resistant to 4-OH Tam and endoxifen, denominated MCF-7Var E; then, the aim of this research was to reverse the acquired resistance of this variant to tamoxifen metabolites by incorporating the natural compound auraptene. Combination treatments of tamoxifen derivatives and auraptene successfully sensitized the chemoresistant MCF-7Var E. Our data suggest a dual regulation of eIF4A and ER by auraptene. Joint treatments of 4-OH Tam and endoxifen with auraptene identified a novel focus for chemoresistance disruption. Synergy was observed using the auraptene molecule and tamoxifen-derived metabolites, which induced a sensitization in MCF-7Var E cells and ERα parental cells that was not observed in triple-negative breast cancer cells (TNBC). Our results suggest a synergistic effect between auraptene and tamoxifen metabolites in a resistant ER+ breast cancer model, which could represent the first step to achieving a pharmacologic strategy.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Local Drug Delivery Systems as Novel Approach for Controlling NETosis in Periodontitis 局部给药系统是控制牙周炎 NETosis 的新方法

IF 5.4 3区医学

Pharmaceutics Pub Date : 2024-09-06 DOI: 10.3390/pharmaceutics16091175

Adina Bianca Boșca, Elena Dinte, Carmen Mihaela Mihu, Alina Elena Pârvu, Carmen Stanca Melincovici, Alina Simona Șovrea, Mariana Mărginean, Anne-Marie Constantin, Anida-Maria Băbțan, Alexandrina Muntean, Aranka Ilea

{"title":"Local Drug Delivery Systems as Novel Approach for Controlling NETosis in Periodontitis","authors":"Adina Bianca Boșca, Elena Dinte, Carmen Mihaela Mihu, Alina Elena Pârvu, Carmen Stanca Melincovici, Alina Simona Șovrea, Mariana Mărginean, Anne-Marie Constantin, Anida-Maria Băbțan, Alexandrina Muntean, Aranka Ilea","doi":"10.3390/pharmaceutics16091175","DOIUrl":"https://doi.org/10.3390/pharmaceutics16091175","url":null,"abstract":"Periodontitis is a chronic inflammation caused by periodontopathogenic bacteria in the dental biofilm, and also involves the inflammatory-immune response of the host. Polymorphonuclear neutrophils (PMNs) play essential roles in bacterial clearance by multiple mechanisms, including the formation of neutrophil extracellular traps (NETs) that retain and destroy pathogens. During PD progression, the interaction between PMNs, NETs, and bacteria leads to an exaggerated immune response and a prolonged inflammatory state. As a lesion matures, PMNs accumulate in the periodontal tissues and die via NETosis, ultimately resulting in tissue injury. A better understanding of the role of NETs, the associated molecules, and the pathogenic pathways of NET formation in periodontitis, could provide markers of NETosis as reliable diagnostic and prognostic tools. Moreover, an assessment of NET biomarker levels in biofluids, particularly in saliva or gingival crevicular fluid, could be useful for monitoring periodontitis progression and treatment efficacy. Preventing excessive NET accumulation in periodontal tissues, by both controlling NETs’ formation and their appropriate removal, could be a key for further development of more efficient therapeutic approaches. In periodontal therapy, local drug delivery (LDD) systems are more targeted, enhancing the bioavailability of active pharmacological agents in the periodontal pocket and surrounding tissues for prolonged time to ensure an optimal therapeutic outcome.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0