RSC Pharmaceutics最新文献

{"title":"Comprehensive physicochemical, biophysical, and <i>in vitro</i> characterization of lung surfactant SP-A peptidomimetics.","authors":"David Encinas-Basurto, Priya Muralidharan, M D Saiful Islam, Ernest L Vallorz, Stephen M Black, Monica Kraft, Julie G Ledford, Heidi M Mansour","doi":"10.1039/d4pm00265b","DOIUrl":"https://doi.org/10.1039/d4pm00265b","url":null,"abstract":"<p><p>Surfactant protein-A (SP-A) is an endogenous and essential lung surfactant-specific protein that is integral to pulmonary immunity, including inhibition of asthma exacerbations. This study aims to comprehensively characterize two peptides (10-AA and 20-AA) of SP-A which confer activity similar to the full-length oligomeric SP-A protein. Spectroscopic and chromatographic analyses revealed that the phosphate (PS) and acetate (AC) salts exhibited distinct solubility and log <i>P</i> partitioning behavior, impacting their physicochemical properties. MD simulations and circular dichroism showed that SP-A 10-AA initially adopts an α-helical structure but loses helicity over time, while SP-A 20-AA remains disordered. Differential scanning calorimetry confirmed variations in thermal stability between salt forms and zeta potential measurements showed that PS salts had a more negative surface charge, potentially influencing membrane interactions. <i>In vitro</i> studies showed high cell viability (>90%) and stable TEER values at the air-liquid interface, confirming biocompatibility and potential epithelial permeability. These findings provide crucial insights into the structural and functional properties of SP-A peptides, supporting their potential as therapeutic agents for pulmonary diseases.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the impact of vitamin D supplement formulation, quality and provision to older adults in UK residential care homes.","authors":"N Rombel, C Lim, A Majeed, S Abdul-Jabbar, G R McClelland, S A Jones","doi":"10.1039/d5pm00003c","DOIUrl":"10.1039/d5pm00003c","url":null,"abstract":"<p><p>Supplying vitamin D supplements to all older adults is beneficial and cost-effective. However, operationalising this supply to residents in long-term care is problematic. This study aimed to understand the challenges of vitamin D supplement provision by auditing the extent of supplementation, measuring the quality of the supplements and investigating the attitudes towards supplement provision in UK care homes. This case study investigated the supply of vitamin D supplement formulations in four UK care homes and analysed the vitamin D content of nine formulation types. It employed semi-structured interviews with care home stakeholders to understand attitudes toward vitamin D supply. Across the nine analysed products, there was >50% variability in their quality (75-137% of the label), but 44% of supplements were of medicinal grade. One tablet from a food-grade product contained 167% vitamin D, and one medicinal-grade tablet only contained 70% vitamin D. Interviews with care home staff highlighted four challenges to providing supplements: the perceived responsibility of healthcare professionals to supplement, difficulties obtaining prescription medications, the absence of national/local strategies, and the financial burden. This study demonstrated sub-optimal vitamin D supplement supply to care home residents, with staff unclear about who was responsible for choosing the correct type of vitamin D supplement, who paid for it, and who was to supply it. This study suggests a new approach to delivering vitamin D supplements to older adults is needed.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic nanoparticles for targeted therapy of liver disease.","authors":"Veena Vijayan, Janitha M Unagolla, Dhruvisha Panchal, Judith Eloyi John, Siddharth S Menon, Jyothi U Menon","doi":"10.1039/d5pm00044k","DOIUrl":"https://doi.org/10.1039/d5pm00044k","url":null,"abstract":"<p><p>Liver fibrosis is a progressive and fatal condition characterized by stiffness and scarring of the liver due to excessive buildup of extracellular matrix (ECM) proteins. If left untreated, it can progress to liver cirrhosis and hepatocellular carcinoma (HCC)-one of the fastest-rising causes of cancer mortality in the United States. Despite the increased prevalence of liver fibrosis due to infections, exposure to toxins, and unhealthy lifestyles, there are no effective treatments available. Recent advances in nanomedicine can lead to more targeted and effective strategies for treating liver diseases than existing treatments. In particular, the use of biomimetic nanoparticles (NPs) such as liposomes and cell-membrane-coated NPs is of interest. NPs functionalized with cell membranes mimic the properties of the source cell used and provide inherent immune evasion ability, homologous adhesion, and prolonged circulation. This review explores the types of biomimetic coatings, different cargoes delivered through biomimetic NPs for various treatment modalities, and the type of core NPs used for targeting liver fibrosis and HCC.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative hygroscopic aerosol particle sizing measurements of the hygroscopic growth of inhaled pharmaceutical ingredients†","authors":"Yiliang Lance Jiang, Josef Kadziola, Jose R. Ruiz, Richard Friend and Jonathan P. Reid","doi":"10.1039/D4PM00310A","DOIUrl":"https://doi.org/10.1039/D4PM00310A","url":null,"abstract":"<p >The size distribution of an inhaled pharmaceutical aerosol generated by a nebulizer is a critical parameter influencing the deposition and therapeutic effect of the medication. Relative humidity (RH) can alter size distribution by promoting particle growth through condensation, depending on the hygroscopicity of the formulation. In this study, we evaluate the effect of RH on mannitol, trehalose, salbutamol, and tobramycin aerosols using the Comparative Hygroscopic Aerosol Particle Sizing (CHAPS) technique under varying RH conditions, ranging from ambient to physiological levels. The results demonstrate that RH significantly influences the aerosol particle size, with particle growth becoming more pronounced as RH exceeds 95%. The findings confirm that understanding the relationship between geometric radial growth factors (rGFs) from single droplet size measurements and the aerodynamic rGF is essential for more accurate prediction of plume size distribution, especially at lower RH levels. We also demonstrate consistency between the size distributions measured by CHAPS and a Next Generation Impactor (NGI), with CHAPS providing higher resolution in size and time and data on actuation-by-actuation variability in size distribution and aerosol dose.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 630-643"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00310a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sometimes less is more: avidity-dependent transport of targeted polymersomes across the blood–brain-barrier†","authors":"Ana Alves, Peter Pfeifer, Andreia Marinho, Claúdia Nunes, Salette Reis, Domingos Ferreira, Marta Correia-da-Silva, Paulo C. Costa, Giuseppe Battaglia, Íris L. Batalha and Cátia D. F. Lopes","doi":"10.1039/D4PM00338A","DOIUrl":"https://doi.org/10.1039/D4PM00338A","url":null,"abstract":"<p >Over the past decade, roughly 10% of new FDA-approved drugs targeted central nervous system (CNS) disorders, while it has been estimated that 98% of small-molecule drugs and nearly all large-molecule therapeutics are unable to cross the blood–brain barrier (BBB). There is a clear need for novel therapeutic modalities that promote receptor-mediated transcytosis modulation and efficiently deliver drugs to the brain. Here, we show that poly(ethylene glycol)-<em>b</em>-poly(lactic acid) (PEG-<em>b</em>-PLA) polymersomes functionalised with a transferrin receptor (TfR)-targeted peptide can effectively deliver a glioblastoma small drug therapeutic (3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone; XGAc) through a two-dimensional model of the BBB and that the transport is dependent on the avidity of the nanoformulation. By adjusting the density of targeting peptides on polymersomes, we present a novel strategy to enhance the efficiency of BBB receptor-mediated transcytosis. These findings highlight the promise of precision-tuned polymersomes in overcoming the BBB and advancing treatments for glioblastoma and other brain diseases.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 535-540"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00338a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccine formulation design: challenges and opportunities","authors":"Saman Zafar, Ambreen Akhtar, Elshaimaa Sayed, Ekhoerose Onaiwu, Muhammad Sohail Arshad and Zeeshan Ahmad","doi":"10.1039/D5PM00017C","DOIUrl":"https://doi.org/10.1039/D5PM00017C","url":null,"abstract":"<p >The rise in activity and multi-faceted impact of infectious agents such as human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented increase in morbidity and mortality around the globe. The spread of infectious diseases at an alarming rate has led to accelerated research on vaccine therapeutics, which can be further exemplified with COVID (coronavirus disease) vaccine development as a global emergency. This review aims to provide insights into vaccine development, components, manufacturing processes, types/platforms and strategies to improve their efficacy. The development of vaccines comprises four stages: (1) exploratory and preclinical, (2) clinical, (3) approval and (4) manufacturing and post-marketing surveillance. Vaccine formulations comprise antigens, adjuvants, preservatives, stabilizers, antibiotics, diluents and trace components. Vaccine manufacturing is a multi-step process involving antigen generation, release, purification, addition of other ingredients (<em>e.g.</em>, adjuvants, preservatives, stabilizers, <em>etc</em>.), quality control testing and filling. Conventional vaccine platforms include live attenuated, inactivated/killed, toxoid, polysaccharide and polysaccharide conjugate, synthetic peptide and virus-like particles. Advanced technologies include viral vectors, bacterial vectors, DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) vaccines. These platforms provide rapid development of vaccines at a relatively low cost compared to conventional counterparts. Several approaches have been adopted for improving vaccine efficacy such as the inclusion of adjuvants and delivery of vaccines <em>via</em> mucosal and transcutaneous routes. Efficient uptake of vaccine antigens by microfold cells (found in the epithelium covering mucosa-associated lymphoid tissues) with subsequent transfer to the underlying antigen-presenting cells provides an efficient vaccine delivery route. In the case of the transcutaneous route, abundant antigen presenting cells found in the skin layer (<em>e.g.</em>, Langerhans) ensure efficient vaccine delivery and induction of potent immune responses. Additionally, both these routes can overcome limitations associated with traditionally employed parenteral routes, such as risk of disease transmission in unhygienic conditions and reuse of contaminated needles, production of biohazardous waste, requirement of trained personnel for administration, invasiveness and poor patient compliance. Identification of conserved pathogenic sequences using advanced genetic engineering methods, machine learning, and artificial intelligence can help in developing efficient vaccines. Moreover, global partnerships, funding and provision of resources from the World Health Organization (WHO) can ensure vaccine development, testing and research activities for developing countries.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 490-516"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00017c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of solid drug nanoparticle dispersions for pulmonary delivery of niclosamide and nitazoxanide via vibrating mesh nebulisation†","authors":"Catherine Unsworth, Andrew B. Dwyer, Alison C. Savage, James J. Hobson, Jonathan Massam, Tom O. McDonald, Paul Curley, Andrew Owen, Andrew O'Sullivan, Ronan MacLoughlin and Steve P. Rannard","doi":"10.1039/D5PM00006H","DOIUrl":"https://doi.org/10.1039/D5PM00006H","url":null,"abstract":"<p >The optimum delivery of very poorly soluble drug compounds is challenging, especially if targeting of disease sites is required. Delivery to the lung is hampered by a range of physiological issues, and inhalation may be the most appropriate route. When breathing is compromised by infection or poor lung capacity, nebulisation may enable therapeutics to be carried deep into the respiratory tract. Here we report the development of nebulised aqueous formulations of two highly water-insoluble drugs with demonstrated anti-SARS-CoV-2 activity and evaluate their pulmonary delivery using <em>in vitro</em> models that include the breathing patterns of children and COVID-19 infected adults.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 517-526"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00006h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox-responsive micellar-like nanoparticles can overcome intrinsic multi-drug resistance in tumour spheroids of triple negative breast cancer†","authors":"Cíntia J. Monteiro, Patrícia F. Monteiro, Alessandra Travanut, Muhammad Gulfam, David M. Heery, Anna Grabowska and Cameron Alexander","doi":"10.1039/D4PM00336E","DOIUrl":"https://doi.org/10.1039/D4PM00336E","url":null,"abstract":"<p >Triple negative breast cancer (TNBC) is one of the most difficult subtypes of breast cancer to treat, due to its aggressiveness, high heterogeneity and lack of targeted therapies. Efforts have been made to elucidate the mechanisms by which TNBC cells become drug-resistant, aiming to identify new molecular targets for the development of effective treatments. Here, we have generated a TNBC 3D multi-cellular spheroid model using MDA-MB-231 cells and assessed the efficacy of drug delivery formulations based on docetaxel (DTX)-loaded micellar-like nanoparticles (MLNP) compared with free DTX. We assessed the viability and the induction of apoptosis in the treated spheroids using established apoptosis and necrosis biomarkers: annexin-V, PI, Sytox and caspase 3 and 7 activity by flow cytometry. Given the efficacy results of the MLNPs and free DTX, the expression of selected genes related to resistance in breast cancer cells was assessed by RT-qPCR (real-time polymerase chain reaction) as well as western blot and immunofluorescence of the drug resistance protein (ABCG2/BCRP) in both 3D and 2D cell culture models of MDA-MB-231 cells. The results from these assays indicate that the TNBC 3D multi-cellular spheroids exhibit an intrinsic multi-drug resistance (MDR) through the up-regulation of ABCG2/BCRP gene and protein, compared to monolayers of the same cell line. Moreover, the results also demonstrate that the MLNPs had the best efficacy against TNBC 3D spheroids whereas the free drug was less efficacious. This suggests that the MLNPs were able to overcome the MDR of the TNBC 3D cell culture model when compared to free DTX.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 644-656"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00336e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive report on biochemical, pharmacological, and pharmacokinetic properties of tool compounds relevant to human pathologies","authors":"Tikam Chand Dakal, Joice K. Joseph, Deepika, Pawan Kumar Maurya, Narendra Kumar Sharma and Senthilkumar Rajagopal","doi":"10.1039/D4PM00331D","DOIUrl":"https://doi.org/10.1039/D4PM00331D","url":null,"abstract":"<p >A tool compound is a reagent that is a selective small-molecule modulator of a protein's activity. It enables researchers to investigate the mechanistic and phenotypic aspects of the molecular target through various experimental approaches, such as biochemical analyses, cell-based assays, or animal investigations. The field of life science research stands to gain significant advantages from the development of research tools that are both more accessible and aesthetically engaging, thereby facilitating the process of hypothesis formation. Target identification and efficacy prediction require novel methodologies due to the declining frequency of new medication approvals and the rising expense of drug development. In this review, we emphasize that chemical probe data collection offers researchers a comprehensive compilation of tool chemicals and also discusses the collection of currently available tool chemicals and highlights limitations in our capacity to target specific biochemical processes through pharmacological means selectively.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 480-489"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00331d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standard purification methods are not sufficient to remove micellular lipophilic dye from polymer nanoparticle solution†","authors":"Eric H. Sterin, Laura A. Weinstein, Chitran Roy Chowdhury, Emma C. Guzzetti and Emily S. Day","doi":"10.1039/D5PM00013K","DOIUrl":"10.1039/D5PM00013K","url":null,"abstract":"<p >Tracking nanoparticles’ location is imperative for understanding cellular interactions, pharmacokinetics, and biodistribution. DiD is a lipophilic dye commonly used to label nanoparticles for trafficking studies. Herein, we show that DiD micelles form in polymer NP solutions during synthesis and can lead to false positive results in downstream assays. Potential methods to remove these micelles are also described.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 527-534"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}