Pub Date : 2025-05-17DOI: 10.1016/j.coph.2025.102543
Claudio Bucolo, Chiara M. Eandi, Sanjoy K. Bhattacharya
{"title":"Editorial overview: Advanced therapies and new targets in ocular diseases","authors":"Claudio Bucolo, Chiara M. Eandi, Sanjoy K. Bhattacharya","doi":"10.1016/j.coph.2025.102543","DOIUrl":"10.1016/j.coph.2025.102543","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102543"},"PeriodicalIF":4.0,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221944","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}
Skin infections are a significant healthcare issue, particularly with rising AMR. LBNs like liposomes, SLNs, and NLCs hold promise for enhancing topical drug delivery in treating skin infections. They improve solubility, stability, and sustained release of antimicrobial agents, allowing deeper skin penetration. Their biocompatibility and ability to encapsulate various drugs make them effective against bacterial and fungal infections. However, challenges such as stability issues (aggregation, fusion, sedimentation, and oxidation), regulatory hurdles (lack of specific guidelines), and manufacturing scalability limit their clinical use. This article reviews the benefits, advancements, and challenges of lipid-based nanocarriers for treating skin infections through topical delivery.
{"title":"Lipid-based nanocarriers in topical applications for skin infections","authors":"Monali M. Upare , Koustubh Mansing Thorawade , Abhay Prakash Mishra , Manisha Nigam , Neti Waranuch","doi":"10.1016/j.coph.2025.102541","DOIUrl":"10.1016/j.coph.2025.102541","url":null,"abstract":"<div><div>Skin infections are a significant healthcare issue, particularly with rising AMR. LBNs like liposomes, SLNs, and NLCs hold promise for enhancing topical drug delivery in treating skin infections. They improve solubility, stability, and sustained release of antimicrobial agents, allowing deeper skin penetration. Their biocompatibility and ability to encapsulate various drugs make them effective against bacterial and fungal infections. However, challenges such as stability issues (aggregation, fusion, sedimentation, and oxidation), regulatory hurdles (lack of specific guidelines), and manufacturing scalability limit their clinical use. This article reviews the benefits, advancements, and challenges of lipid-based nanocarriers for treating skin infections through topical delivery.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102541"},"PeriodicalIF":4.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204841","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}
Pub Date : 2025-05-15DOI: 10.1016/j.coph.2025.102542
Vishin Patil , Pooja S. Patil , Mugdha Vasant Kulkarni , Suraj Nijamso Pattekari , Zamir G. Khan
Traditional antibiotic delivery methods face limitations including, systemic toxicity and poor bioavailability. Transdermal microneedle (MN) arrays bypass skin barriers, enhancing antibiotic penetration while minimizing resistance risks. This review examines advanced MN systems such as solid, coated, hollow, dissolvable, and smart stimuli-responsive, highlighting design innovations, nanomaterial integration, and preclinical efficacy against infections like methicillin-resistant Staphylococcus aureus (MRSA). While MN technology enables targeted, minimally invasive delivery, clinical adoption requires overcoming scalability hurdles and demonstrating real-world efficacy. Comprehensive clinical validation remains essential to translate these systems into mainstream solutions for combating antibiotic resistance and improving chronic wound management.
Pub Date : 2025-05-10DOI: 10.1016/j.coph.2025.102537
Enoch Tin , Jongbok Lee , Li Zhang
CD3+CD4−CD8− double-negative T cells (DNTs) represent a unique subset of T lymphocytes with potent cytotoxicity against acute myeloid leukemia (AML). Importantly, allogeneic DNTs do not induce graft-versus-host disease and have demonstrated characteristics suitable for off-the-shelf cellular therapy with promising efficacy in early-stage clinical trials. DNT therapy can synergize with conventional AML treatments and can be transduced with chimeric antigen receptors (CARs). Notably, persistent CAR+ T cells in patients, who achieved long-term remission, predominantly have a DNT phenotype. The unique and versatile therapeutic properties of allogeneic DNTs position them as a strong candidate among adoptive cellular therapies for AML.
{"title":"Allogeneic double-negative T-cell therapy for acute myeloid leukemia","authors":"Enoch Tin , Jongbok Lee , Li Zhang","doi":"10.1016/j.coph.2025.102537","DOIUrl":"10.1016/j.coph.2025.102537","url":null,"abstract":"<div><div>CD3<sup>+</sup>CD4<sup>−</sup>CD8<sup>−</sup> double-negative T cells (DNTs) represent a unique subset of T lymphocytes with potent cytotoxicity against acute myeloid leukemia (AML). Importantly, allogeneic DNTs do not induce graft-versus-host disease and have demonstrated characteristics suitable for off-the-shelf cellular therapy with promising efficacy in early-stage clinical trials. DNT therapy can synergize with conventional AML treatments and can be transduced with chimeric antigen receptors (CARs). Notably, persistent CAR<sup>+</sup> T cells in patients, who achieved long-term remission, predominantly have a DNT phenotype. The unique and versatile therapeutic properties of allogeneic DNTs position them as a strong candidate among adoptive cellular therapies for AML.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102537"},"PeriodicalIF":4.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155159","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}
Infectious skin diseases represent a major global health burden, demanding effective and affordable treatments. Conventional therapies often face challenges such as reduced bioavailability, enzymatic degradation, low permeability, and poor solubility. Colloidal-based transdermal drug delivery systems, including liposomes, ethosomes, niosomes, nanoemulsions, polymeric nanoparticles, micelles, solid lipid nanoparticles, etc., have emerged as promising alternatives. In brief, these colloidal systems enhance drug penetration, stability, biocompatibility, and customized release while improving antimicrobial efficacy against various pathogens and minimizing systemic side effects. In conclusion, colloidal formulations offer a targeted, efficient approach, optimizing therapeutic outcomes, improving patient compliance, and advancing the treatment of infectious skin diseases.
{"title":"Colloidal drug delivery systems for infectious diseases of skin","authors":"Sopan Nangare , Varda Joshi , Shrikant Magdum , Riya Patil , Vishin Patil","doi":"10.1016/j.coph.2025.102536","DOIUrl":"10.1016/j.coph.2025.102536","url":null,"abstract":"<div><div>Infectious skin diseases represent a major global health burden, demanding effective and affordable treatments. Conventional therapies often face challenges such as reduced bioavailability, enzymatic degradation, low permeability, and poor solubility. Colloidal-based transdermal drug delivery systems, including liposomes, ethosomes, niosomes, nanoemulsions, polymeric nanoparticles, micelles, solid lipid nanoparticles, etc., have emerged as promising alternatives. In brief, these colloidal systems enhance drug penetration, stability, biocompatibility, and customized release while improving antimicrobial efficacy against various pathogens and minimizing systemic side effects. In conclusion, colloidal formulations offer a targeted, efficient approach, optimizing therapeutic outcomes, improving patient compliance, and advancing the treatment of infectious skin diseases.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102536"},"PeriodicalIF":4.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168264","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}
Pub Date : 2025-05-08DOI: 10.1016/j.coph.2025.102528
Amal El Daibani , Gwendolyn Burgess , Lauren Rysztak , Emily Jutkiewicz , Amynah A. Pradhan
The delta opioid receptor (DOR) is an often-overlooked member of the opioid receptor family, lacking the euphoric and addictive effects of mu receptors and the dysphoric properties of kappa. Instead, the DOR functions to restore balance, showing minimal impact in acute pain but alleviating allodynia and hyperalgesia associated with chronic pain and producing anxiolytic and antidepressant-like behaviors. Though past clinical trials for osteoarthritis and depression were unsuccessful, emerging evidence supports DOR’s therapeutic potential in migraine, substance use disorder, irritable bowel syndrome, and metabolic disorder. Advances in pharmacology, including structure-guided design and intracellular targeting, offer promising new directions for DOR-based drug development.
{"title":"Delta opioid receptors: Overlooked outlier or the next big thing","authors":"Amal El Daibani , Gwendolyn Burgess , Lauren Rysztak , Emily Jutkiewicz , Amynah A. Pradhan","doi":"10.1016/j.coph.2025.102528","DOIUrl":"10.1016/j.coph.2025.102528","url":null,"abstract":"<div><div>The delta opioid receptor (DOR) is an often-overlooked member of the opioid receptor family, lacking the euphoric and addictive effects of mu receptors and the dysphoric properties of kappa. Instead, the DOR functions to restore balance, showing minimal impact in acute pain but alleviating allodynia and hyperalgesia associated with chronic pain and producing anxiolytic and antidepressant-like behaviors. Though past clinical trials for osteoarthritis and depression were unsuccessful, emerging evidence supports DOR’s therapeutic potential in migraine, substance use disorder, irritable bowel syndrome, and metabolic disorder. Advances in pharmacology, including structure-guided design and intracellular targeting, offer promising new directions for DOR-based drug development.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102528"},"PeriodicalIF":4.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189767","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}
Pub Date : 2025-04-26DOI: 10.1016/j.coph.2025.102527
Raffaele Palmieri , Luca Maurillo , Maria Ilaria Del Principe , Adriano Venditti , Francesco Buccisano
Acute Myeloid Leukemia (AML) is a complex disease whose outcome can be variably influenced by several clinical and biological factors. Although there is still no consensus on how to integrate these elements to best guide treatment choice, multiparametric models, commonly called fitness scores, have been developed to evaluate each patient's ability to tolerate therapies. These models consider various risk factors, including disease biology, comorbidities, physical and cognitive function. To date, several scoring systems can be used to categorize patients on their fitness for intensive or non-intensive therapies. However, existing tools mainly focus on identifying patients suitable for conventional intensive chemotherapy and fail to address the complexities of less-fit patients who might benefit from innovative intensive, less-intensive, and even maintenance strategies. As treatment landscapes are in constant evolution, identifying intermediate level of fitness through recalibration of existing scores or development of new ones should be prioritized. Considering all the above, this review aims to report on the state of the art of fitness assessment in AML and discuss possible future directions on this topic.
{"title":"Fitness in acute myeloid leukemia, state of the art and future directions","authors":"Raffaele Palmieri , Luca Maurillo , Maria Ilaria Del Principe , Adriano Venditti , Francesco Buccisano","doi":"10.1016/j.coph.2025.102527","DOIUrl":"10.1016/j.coph.2025.102527","url":null,"abstract":"<div><div>Acute Myeloid Leukemia (AML) is a complex disease whose outcome can be variably influenced by several clinical and biological factors. Although there is still no consensus on how to integrate these elements to best guide treatment choice, multiparametric models, commonly called fitness scores, have been developed to evaluate each patient's ability to tolerate therapies. These models consider various risk factors, including disease biology, comorbidities, physical and cognitive function. To date, several scoring systems can be used to categorize patients on their fitness for intensive or non-intensive therapies. However, existing tools mainly focus on identifying patients suitable for conventional intensive chemotherapy and fail to address the complexities of less-fit patients who might benefit from innovative intensive, less-intensive, and even maintenance strategies. As treatment landscapes are in constant evolution, identifying intermediate level of fitness through recalibration of existing scores or development of new ones should be prioritized. Considering all the above, this review aims to report on the state of the art of fitness assessment in AML and discuss possible future directions on this topic.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102527"},"PeriodicalIF":4.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947657","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}
Pub Date : 2025-04-08DOI: 10.1016/j.coph.2025.102526
Bofei Wang , Patrick K. Reville , Hussein A. Abbas
Acute myeloid leukemia (AML) is an aggressive and highly heterogeneous hematological malignancy characterized by clonal expansion and differentiation arrest in myeloid progenitor cells. Despite advancements in chemotherapy, allogeneic hematopoietic stem cell transplantation, and post-remission maintenance therapies, the long-term survival remains unsatisfactory with high rates of relapse and refractory. These therapeutic challenges are mediated by multiple factors, including the complexity of the cellular hierarchies in AML, the interaction of leukemic stem cells (LSCs) with the bone marrow niche, inflammation, and immune evasion mechanisms. Further, the absence of specific surface markers that distinguish LSCs from normal hematopoietic stem cells, together with LSCs’ functional heterogeneity, complicates targeted treatment approaches. Immune dysfunction, including T cell exhaustion and immune suppression within the bone marrow niche contributes to therapy resistance. In this brief review, we aim to explore current challenges in AML therapy, focusing on LSC-driven resistance, immune evasion, and the need for innovative therapeutic strategies.
{"title":"Therapeutic hurdles in acute myeloid leukemia: Leukemic stem cells, inflammation and immune dysfunction","authors":"Bofei Wang , Patrick K. Reville , Hussein A. Abbas","doi":"10.1016/j.coph.2025.102526","DOIUrl":"10.1016/j.coph.2025.102526","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is an aggressive and highly heterogeneous hematological malignancy characterized by clonal expansion and differentiation arrest in myeloid progenitor cells. Despite advancements in chemotherapy, allogeneic hematopoietic stem cell transplantation, and post-remission maintenance therapies, the long-term survival remains unsatisfactory with high rates of relapse and refractory. These therapeutic challenges are mediated by multiple factors, including the complexity of the cellular hierarchies in AML, the interaction of leukemic stem cells (LSCs) with the bone marrow niche, inflammation, and immune evasion mechanisms. Further, the absence of specific surface markers that distinguish LSCs from normal hematopoietic stem cells, together with LSCs’ functional heterogeneity, complicates targeted treatment approaches. Immune dysfunction, including T cell exhaustion and immune suppression within the bone marrow niche contributes to therapy resistance. In this brief review, we aim to explore current challenges in AML therapy, focusing on LSC-driven resistance, immune evasion, and the need for innovative therapeutic strategies.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102526"},"PeriodicalIF":4.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899387","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}
Pub Date : 2025-04-08DOI: 10.1016/j.coph.2025.102524
Gordon Victor Hoffmann , Adrian Gottschlich , Marion Subklewe , Sebastian Kobold
Identifying safe and effective CAR T cell targets in acute myeloid leukemia (AML) is challenging due to the disease’s complexity and overlap with normal hematopoiesis. This review highlights advances in target discovery for AML, emphasizing innovative approaches. Structural surfaceomics identifies tumor-specific protein conformations, while AI-driven single-cell RNA sequencing integrates multi-source data to pinpoint optimal targets. Refined cell surface capture technology maps the AML surfaceome without relying on predefined antibodies. These strategies enhance CAR T cell specificity and minimize off-tumor effects, offering promising pathways for safer and more effective AML treatments and broader cancer therapies.
{"title":"Novel approaches to CAR T cell target identification in acute myeloid leukemia","authors":"Gordon Victor Hoffmann , Adrian Gottschlich , Marion Subklewe , Sebastian Kobold","doi":"10.1016/j.coph.2025.102524","DOIUrl":"10.1016/j.coph.2025.102524","url":null,"abstract":"<div><div>Identifying safe and effective CAR T cell targets in acute myeloid leukemia (AML) is challenging due to the disease’s complexity and overlap with normal hematopoiesis. This review highlights advances in target discovery for AML, emphasizing innovative approaches. Structural surfaceomics identifies tumor-specific protein conformations, while AI-driven single-cell RNA sequencing integrates multi-source data to pinpoint optimal targets. Refined cell surface capture technology maps the AML surfaceome without relying on predefined antibodies. These strategies enhance CAR T cell specificity and minimize off-tumor effects, offering promising pathways for safer and more effective AML treatments and broader cancer therapies.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102524"},"PeriodicalIF":4.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892136","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}
Pub Date : 2025-04-04DOI: 10.1016/j.coph.2025.102525
Memnon Lysandrou, Robert Zeiser
Acute myeloid leukaemia (AML) was an incurable disease prior to allogeneic haematopoietic cell transplantation (allo-HCT), which was proven to be a potent cellular immunotherapy-approach. However, allo-HCT has major side effects, with disease relapse presenting as a frequent complication. Novel immunotherapies aim to reduce toxicity and increase the anti-leukaemia activity of allo-HCT. Technological advancements in genetic engineering approaches enable potent immunotherapeutic activity while limiting toxicities. A biology-driven application of small molecules that target AML vulnerabilities holds promise to enhance anti-leukaemia immunotherapy. Extensive preclinical testing of these approaches is essential to reduce toxicity and to find the ideal combination partners for future clinical testing.
{"title":"Strategies to enhance anti-leukaemia immunotherapy","authors":"Memnon Lysandrou, Robert Zeiser","doi":"10.1016/j.coph.2025.102525","DOIUrl":"10.1016/j.coph.2025.102525","url":null,"abstract":"<div><div>Acute myeloid leukaemia (AML) was an incurable disease prior to allogeneic haematopoietic cell transplantation (allo-HCT), which was proven to be a potent cellular immunotherapy-approach. However, allo-HCT has major side effects, with disease relapse presenting as a frequent complication. Novel immunotherapies aim to reduce toxicity and increase the anti-leukaemia activity of allo-HCT. Technological advancements in genetic engineering approaches enable potent immunotherapeutic activity while limiting toxicities. A biology-driven application of small molecules that target AML vulnerabilities holds promise to enhance anti-leukaemia immunotherapy. Extensive preclinical testing of these approaches is essential to reduce toxicity and to find the ideal combination partners for future clinical testing.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102525"},"PeriodicalIF":4.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860016","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}
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