RSC Pharmaceutics最新文献

{"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}

{"title":"Artesunate-loaded bilosomes with enhanced oral bioavailability: in silico and in vitro study against Leishmania donovani promastigotes and in vivo pharmacokinetic assessment in rats","authors":"Hitesh Wankhede, Sudha Madhavi Penumaka, Debabrata Mandal, Supada Rojatkar, Vinod Gaikwad and Sharvil Patil","doi":"10.1039/D5PM00025D","DOIUrl":"https://doi.org/10.1039/D5PM00025D","url":null,"abstract":"<p >The deadly parasite disease known as visceral leishmaniasis (VL) is caused by the protozoa of <em>Leishmania donovani</em>. Artesunate (ART) has been reported to act against VL. However, its medical use is limited owing to the fact that it belongs to BCS class II. Thus, the aim of the present work was to prepare ART-loaded bilosomes (ART-BIL) to mitigate the drawbacks associated with ART. Box–Behnken design was used to optimize ART-BIL prepared by the ethanol injection method. ART-BIL were characterized for vesicle size, entrapment efficiency, FTIR, DSC, TEM, <em>in vitro</em> drug release, <em>in silico</em> molecular docking, <em>in vitro</em> antileishmanial activity against <em>Leishmania donovani</em>, and <em>in vivo</em> pharmacokinetic assessment. The optimized spherical ART-BIL was found to have a vesicle size of 186.7 ± 15.0 nm and an entrapment efficiency of 95.36 ± 2.5%. Spherical, non-aggregated vesicles demonstrated a biphasic drug release profile with a remarkable increase in the dissolution rate of artesunate compared to an artesunate dispersion. <em>In silico</em> molecular docking studies revealed the antileishmanial potential of artesunate and chenodeoxycholic acid by binding them to glyceraldehyde 3-phosphate dehydrogenase (G3PDH). Further, <em>in vitro</em> antileishmanial studies showed a significant enhancement in the antileishmanial potential of artesunate while <em>in vivo</em> pharmacokinetic studies demonstrated 1.39 and 1.47 fold increases in the <em>C</em><small>_max</small> and AUC of ART when formulated into bilosomes. ART-loaded bilosomes could be a promising drug delivery system for the treatment of visceral leishmaniasis.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 541-552"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00025d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100116","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":"Comparison of macromolecule permeation through extracellular matrix and hyaluronic acid to inform in vitro testing of subcutaneous therapies","authors":"Jana Javorovic, Belal I. Hanafy, Frans Franek and Driton Vllasaliu","doi":"10.1039/D4PM00271G","DOIUrl":"https://doi.org/10.1039/D4PM00271G","url":null,"abstract":"<p >Subcutaneous injection is a widely used route of drug administration, but biopredictive <em>in vitro</em> tools for predicting <em>in vivo</em> bioavailability are not widely established. One such system, the subcutaneous injection site simulator (SCISSOR), incorporates hyaluronic acid (HA) as a model of the subcutaneous extracellular matrix (ECM), which dictates the diffusion of test compounds. However, the native ECM found is markedly more complex. Here for the first time, we compared the permeation of macromolecules with different physicochemical properties (molecular weight and charge) and model biological molecules across the HA hydrogel (used in SCISSOR) and an animal-derived basement membrane extract (BME), an ECM. We coated tissue culture inserts with these matrices as a simple experimental set up to test the permeation. The results show that the two matrices displayed similarities and some notable differences in their performance as barriers for macromolecules of different properties, suggesting that a simple experimental setup utilising biologically derived ECM may act as an inexpensive and accessible tool to predict the <em>in vivo</em> performance of biotherapeutics for SC administration.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 624-629"},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00271g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100160","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":"Polysaccharide-capped silver nanoparticles impregnated cream for the efficient management of wound healing†","authors":"H. P. Syama, B. S. Unnikrishnan, J. Sreekutty, M. G. Archana, G. U. Preethi, P. L. Reshma and T. T. Sreelekha","doi":"10.1039/D4PM00274A","DOIUrl":"https://doi.org/10.1039/D4PM00274A","url":null,"abstract":"<p >Developing wound-dressing materials that meet all the required qualities for curing burns and injuries caused by various diseases is a challenging task. However, the biocompatibility, biodegradability, and non-toxicity of natural polysaccharides make them an excellent base material for creating flexible and widely accepted formulations. To test this, we created a cream formulation that utilised galactomannan's non-toxic and immuno-stimulatory properties and added silver nanoparticles to create SNP@PSP. Preclinical studies were conducted <em>in vitro</em> and <em>in vivo</em> experiments in rat models to test the wound-healing capabilities of the formulation. The cream's ability to heal wounds was demonstrated through immunohistochemistry, collagen staining, and histopathology. Our work provides a formulation that utilises silver nanoparticles to create polysaccharide cream with improved biocompatibility and antibacterial properties. The rat wound-healing experiments showed that the cream was effective for clinical use, with the addition of nanosilver significantly boosting its antibacterial properties.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 570-580"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00274a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100117","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":"Polybasic nanogels for intracellular co-delivery of paclitaxel and carboplatin: a novel approach to ovarian cancer therapy†","authors":"Angela M. Wagner, Olivia L. Lanier, Ani Savk and Nicholas A. Peppas","doi":"10.1039/D4PM00330F","DOIUrl":"10.1039/D4PM00330F","url":null,"abstract":"<p >Ovarian cancer is one of the leading causes of cancer-related deaths in women, with limited progress in treatments despite decades of research. Common treatment protocols rely on surgical removal of tumors and chemotherapy drugs, such as paclitaxel and carboplatin, which are capable of reaching cancer cells throughout the body. However, the effectiveness of these drugs is often limited due to toxic reactions in patients, nonspecific drug distribution affecting healthy cells, and the development of treatment resistance. In this study, we introduce a polybasic nanogel system composed of poly(diethylaminoethyl methacrylate-<em>co</em>-cyclohexyl methacrylate)-<em>g</em>-poly(ethylene glycol) designed for the targeted co-delivery of paclitaxel and carboplatin directly to ovarian cancer cells. These nanogel systems can respond to the cellular microenvironment to achieve controlled, on-demand drug release, reducing off-target effects and enhancing therapeutic uptake. Additionally, we investigated nanoparticle degradation and controlled drug release as a function of various crosslinkers, including tetraethylene glycol dimethacrylate, bis(2-methacryloyl)oxyethyl disulfide, poly(lactic acid)-<em>b</em>-poly(ethylene glycol)-<em>b</em>-poly(lactic acid)dimethacrylate, and polycaprolactone dimethacrylate. Our results, using OVCAR-3 human ovarian cancer cells, demonstrated that this dual-delivery system outperformed free drugs in inducing cancer cell death, representing a promising advance in the field of nanoparticle-based therapies for ovarian cancer. By loading two chemotherapeutic agents into a single, environmentally responsive particle, this approach shows the potential to overcome common resistance mechanisms and achieve more effective tumor suppression. In summary, by delivering chemotherapy more precisely, it may be possible to enhance therapeutic outcomes while minimizing toxicity and nonspecific drug distribution, ultimately improving patient quality of life.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 553-569"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485245","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":"Strategies to overcome antibiotic resistance: silver nanoparticles and vancomycin in pathogen eradication","authors":"Sakshi V. Khairnar, Ashish Das, David Oupický, Marat Sadykov and Svetlana Romanova","doi":"10.1039/D4PM00314D","DOIUrl":"https://doi.org/10.1039/D4PM00314D","url":null,"abstract":"<p >The increasing prevalence of antibiotic resistance presents a significant challenge to public health, undermining the efficacy of conventional antibiotic treatments. Given the scarcity of new antibiotics and efficient preventive strategies, the exploration of alternative treatments has become imperative. For many years, vancomycin, a glycopeptide antibiotic, has been considered a last resort for treating severe Gram-positive bacterial infections. However, the emergence of vancomycin-resistant bacteria has raised significant concerns. The expanding use of nanomaterials in healthcare settings has shifted the spotlight towards innovative antibacterial nanomaterials, potentially offering solutions to the resistance crisis. One of the promising approaches to combat resistance involves employing metal nanoparticles to enhance antibiotic efficacy. Silver nanoparticles (AgNPs) have garnered particular interest due to their extensively documented broad-spectrum and robust antimicrobial properties, especially against bacterial biofilms, making them useful against multidrug-resistant pathogens. Recent evidence suggests synergistic antibacterial activity when AgNPs are combined with vancomycin. This innovative approach offers the potential to mitigate associated side effects and improve susceptibility to resistant strains. Consequently, the combination of vancomycin and AgNPs presents a compelling strategy for addressing bacterial infections. This review delves into the interactions between AgNPs and vancomycin, providing valuable insights into combating antibiotic resistance. Current research efforts continue to investigate and underscore the advancement of formulation strategies and their performance evaluation in a wide array of infection paradigms. This continuing work aims to enhance our understanding of drug delivery systems and their therapeutic potential across various infectious diseases.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 455-479"},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00314d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100111","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":"Comparison of polymer-coated, drug-eluting self-expandable metal stents for the potential treatment of gastrointestinal cancers†","authors":"Mohammad Arafat, Anthony Wignall, Kyle Brewer, Yunmei Song, Hugo Albrecht, Clive A. Prestidge, Sanjay Garg and Anton Blencowe","doi":"10.1039/D4PM00312H","DOIUrl":"https://doi.org/10.1039/D4PM00312H","url":null,"abstract":"<p >Self-expandable metal stents (SEMS) represent the gold standard for the clinical management of malignant obstructions in the gastrointestinal tract. Gastrointestinal stent blockage (restenosis) caused by tumour growth is a common problem. The incorporation of anticancer drugs into SEMS for localised delivery could potentially address restenosis, although further studies are required to better understand the influence of the stent structure in combination with different drug-eluting polymer formulations and chemotherapeutics. Therefore, in this work, we investigated for the first time the suitability of a polyurethane-silicone (PUS) elastomer for the controlled encapsulation and release of 5-fluorouracil (5FU) from membrane-covered oesophageal stents (<strong>OS</strong>) and bare enteral colonic stents (<strong>CS</strong>). The stents were coated with a bilayer structure consisting of a 5FU-loaded (7.0% w/w) PUS basecoat and poly(ethylene-<em>co</em>-vinyl acetate) (PEVA) diffusion regulating topcoat. Physicochemical characterisation of the coatings revealed that 5FU is uniformly distributed and semi-crystalline in the PUS layer, and that 5FU did not leach into the topcoat during coating. Interestingly, drug release from the coated stents revealed a significant difference, with 5FU release from CS plateauing after ∼12 d, while a much more gradual release was observed with the OS over 150 d. Imaging revealed that defects in the coatings due to the underlying stent structure are likely contributors to these differences. The coated stents were found to be stable to gamma sterilisation and in accelerated stability tests. <em>In vitro</em> cytotoxicity, cell cycle and apoptosis assays revealed that 5FU released from the stents had comparable anticancer efficacy to free 5FU against human colon carcinoma cells. This research demonstrates the potential of polymer-coated SEMS for controlled drug-release and highlights the importance of the underlying stent structure on performance.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 611-623"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00312h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100120","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":"3D printing of tailored veterinary dual-release tablets: a semi-solid extrusion approach for metoclopramide†","authors":"Rathna Mathiyalagan, Max Westerlund, Alaa Mahran, Rabia Altunay, Jarkko Suuronen, Mirja Palo, Johan O. Nyman, Eero Immonen, Jessica M. Rosenholm, Erica Monaco and Xiaoju Wang","doi":"10.1039/D4PM00322E","DOIUrl":"https://doi.org/10.1039/D4PM00322E","url":null,"abstract":"<p >Metoclopramide (MCP) is frequently used to control nausea and vomiting in animals, but its short half-life requires it to be administered thrice daily. In addition, commercial veterinary MCP formulations are currently lacking. As a result, veterinary practitioners often resort to off-label use of human medications, which can lead to inconsistent patient outcomes and complications arising from inadequate dosing. Thus, there is a growing recognized need for individualized treatment strategies also within veterinary practice, as they can offer tailored doses and improved options for animal patients. To address this unmet need and overcome these challenges, our study focused on developing a once-daily dual-release tailored dose for different-sized cats and dogs utilizing semi-solid extrusion (SSE) 3D printing. The dual-release system containing different cellulosic polymers is designed to provide a rapid onset and sustained action to ensure prolonged drug release and minimize the frequency of administration. The produced printing ink formulations were successfully used to obtain different-sized tailored doses with a significant correlation between the designs and the obtained drug amounts. Dissolution studies revealed the impact of polymer combinations and tablet surface area on drug release profiles. Kinetic modeling indicated that both diffusion and erosion are involved in the release mechanisms. This research emphasizes the practical use of SSE 3D printing in developing dual-release delivery systems by producing precise and pet-friendly tailored tablets to enhance veterinary treatments close to the point-of-care.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 413-426"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00322e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637977","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 review on glioblastoma: nanotechnology, immunotherapy and combined therapeutic approaches","authors":"Ashish Dhiman, Yagni Shah, Dhwani Rana and Kalpna Garkhal","doi":"10.1039/D4PM00263F","DOIUrl":"https://doi.org/10.1039/D4PM00263F","url":null,"abstract":"<p >Glioblastoma multiforme (GBM) is the most dangerous type of brain cancer because of spontaneous microvascular growth, which leads to damage to nearby brain tissues. GBM affects a huge population across the globe and current therapies for GBM have not proven fruitful in past decades due to poor clinical prognosis. The slow progression of GBM makes it difficult to track during diagnosis for treatment. Thus, there is a need to develop some cutting-edge drug delivery platforms, which could overcome the challenges faced in the delivery of current therapeutic drugs. Nanotechnology has been an emerging paradigm to unravel promising drug therapies, be they immunotherapy or combination therapy. The surface modification of nanocarriers led to significant improvements in therapeutic aspects of GBM. The surface-modified entities could be monoclonal antibodies, functional peptides, growth inhibitors, folic acid, transferrin, or lectins. Immunotherapeutic interventions, such as vaccines, oncolytic virotherapy, immune checkpoint inhibitors, and CAR T-cell and N-k cell therapies, are rising as a treatment model for GBM. Future research must elaborate on remedies that can encounter problems with current treatment. However, numerous research studies are underway to explore new treatments. The current review reveals potential future therapies to challenge the issues faced in the treatment of GBM. Nanotechnology-based drug carriers, surface modification of nanocarriers for enhanced drug delivery to GBM and immunotherapeutic approaches are enlisted. The review also discusses multi-modal approaches to tackle resistance and others issues related to monotherapy.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 207-234"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00263f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638116","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}