RSC Pharmaceutics最新文献

{"title":"Systematic screening of excipients to stabilize aerosolized lipid nanoparticles for enhanced mRNA delivery.","authors":"Brittany J Heiser, Mae M Lewis, Meysam Mohammadi Zerankeshi, Emily K Netemeyer, Ashlee M Hernandez, Alexander E Marras, Debadyuti Ghosh","doi":"10.1039/d5pm00061k","DOIUrl":"10.1039/d5pm00061k","url":null,"abstract":"<p><p>Aerosolized lipid nanoparticles (LNPs) delivering mRNA are an attractive strategy for use in local, inhalable therapy to treat patients with lung diseases. However, a major barrier to delivering aerosolized mRNA LNPs is the shear forces encountered during aerosolization. These forces lead to significant morphology changes and subsequent decrease in efficacy of mRNA delivery. To best retain the physicochemical properties of mRNA LNPs during aerosolization, we took a formulation-based strategy to stabilize LNPs. We used a design-of-experiment (DOE) approach to comprehensively screen rationally chosen excipients at multiple concentrations. Excipients were carefully selected based on their use in clinically approved inhaled products or their ability to support lipid membrane properties. These excipients were added to the same mRNA LNP composition after formulation, were subsequently characterized, and used to transfect human lung cells at air-liquid interface. From this systematic screen, we identified that the addition of our lead candidate, poloxamer 188, best stabilizes LNP size throughout aerosolization and enhances mRNA expression after aerosolization. Additional morphological studies of the inclusion of poloxamer 188 in LNPs suggests that the excipient lowers aerosolization induced fusion or aggregation of particles without altering the internal structure. Our results indicate that poloxamer 188 can support aerosolized mRNA LNP delivery by maintaining LNP size and significantly enhancing therapeutic nucleic acid delivery to lung cells.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677128","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":"Breaking the cellular delivery bottleneck: recent developments in direct cytosolic delivery of biologics.","authors":"Harini Nagaraj, Victor Lehot, Nourina Nasim, Yagiz Anil Cicek, Ritabrita Goswami, Taewon Jeon, Vincent M Rotello","doi":"10.1039/d5pm00129c","DOIUrl":"10.1039/d5pm00129c","url":null,"abstract":"<p><p>Proteins and nucleic acid therapeutics represent a significant and growing share of the pharmaceutical landscape. The majority of biological and therapeutic applications of these biomolecules require access to the cytosol. Delivery of biologics directly to the cytosol is made difficult by the impermeability of the cell membrane. As a result, most delivery strategies have utilized endocytic uptake pathways to deliver biologics into the cell. However, endosomally entrapped cargo often faces limited escape efficiency and is prone to degradation within endo/lysosomal compartments. The emergence of delivery vehicles capable of bypassing endocytosis and directly traversing the cell membrane offers a promising approach to improve the cytosolic delivery efficiency of biomolecules. Here, we highlight recent developments in endocytosis-independent delivery systems for biologics and ways to accurately assess cytosolic delivery of biologics. Strategies employing covalent and non-covalent modification of biomolecules will be reviewed, along with strategies incorporating both covalent and supramolecular processes.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602751","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":"Babassu oil-based microemulsion promotes uniform in vitro release of diclofenac sodium and donepezil hydrochloride†","authors":"Felipe Schlichta de Gouveia, Gabriela Spingolon and Tanira Alessandra Silveira Aguirre","doi":"10.1039/D5PM00022J","DOIUrl":"https://doi.org/10.1039/D5PM00022J","url":null,"abstract":"<p >Microemulsions are nanostructured and thermodynamically stable systems with a reduced droplet size. They can improve drug absorption and distribution. Babassu oil has been investigated for various therapeutic properties reported by popular use. This work aimed to develop, optimize, and characterize babassu oil-based water-in-oil microemulsions to promote a controlled and uniform release of drugs with different physicochemical properties. The optimal microemulsion composition was investigated through pseudoternary diagrams, with water, surfactant mixture, and oil mixture as vertices. The formulations were characterized based on pH, conductivity, size, polydispersity index, and drug content. <em>In vitro</em> drug release was carried out using multidimensional and unidimensional techniques. An optimum microemulsion contains (w/w): 10% water, 17.8% babassu oil, 26.2% medium-chain triglycerides, 29.7% Span™ 83, 7.1% Tween® 80, and 9.2% Transcutol® HP. Diclofenac sodium (DS), donepezil hydrochloride (DH), and insulin were associated with the dispersed phase of the microemulsion. These formulations presented a droplet size of 26.9 ± 1.9, 22.6 ± 0.4, and 35.5 ± 0.7 nm, respectively. The polydispersity index was &lt;0.1 for all formulations. Microemulsions controlled the outflow of drugs, showing a uniform release compared to the respective controls. It was evidenced that these profiles depend on the features of the molecule associated. According to the selection criteria, most experimental DS and DH release kinetics in water or pH 7.2 fit well with the Gompertz model. In conclusion, a babassu oil-based water-in-oil microemulsion was developed for the first time, optimized, and characterized, supporting further investigation of the formulation as a drug delivery system.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 824-837"},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00022j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624159","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":"Vascular benefit of the use of mepivacaine as an anaesthetic in resilient hyaluronic acid® injectables","authors":"Jimmy Faivre, Romain Brusini, Jing Jing, Sabrina Walley, Lukas Roubenne, François Bourdon, Lee Walker, Bruno Le Grand and Conor J. Gallagher","doi":"10.1039/D5PM00069F","DOIUrl":"https://doi.org/10.1039/D5PM00069F","url":null,"abstract":"<p >The use of lidocaine (0.3% w/w) for pain management in hyaluronic acid-based soft-tissue injectables has been standard for two decades. Given lidocaine's well-known vasodilatory activity it may contribute to the incidence of post-treatment adverse events including bruising in patients. This study seeks to compare these vasodilatory properties of lidocaine with that of another anaesthetic candidate, mepivacaine. Rat aortic rings and human skin resistance arteries (diameter between 200–400 μm) were mounted on an isolated organ bath or myograph, respectively, and exposed to progressively increasing concentrations of lidocaine or mepivacaine from a solution or released from a gel. The concentration-dependent vascular response and kinetics were systematically compared in tissue originating from 3 biological donors. Additionally, tissue perfusion changes induced by 0.3% w/w anaesthetic solutions were assessed using laser Doppler imaging in rabbit ears. Systematically, lidocaine exhibited a greater vasodilatory activity than mepivacaine in clinically relevant concentration ranges in both animal and human models. In contrast to lidocaine, mepivacaine did not have a significant impact on blood vessel vasodilation. In clinical practice, formulation of hyaluronic acid (HA) injectables with mepivacaine may potentially reduce the risk of common adverse events. This characteristic highlights its potential advantages in the practice of hydrogel injections.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 814-823"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00069f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624158","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":"Glivec to generic imatinib switch: in vitro comparative dissolution assessment, bioequivalence, safety, and tolerability of 400 mg imatinib tablets in healthy volunteers","authors":"Samir Das, Saurav Sarkar, Ranabir Sahu, Tarun Kumar Dua, Paramita Paul and Gouranga Nandi","doi":"10.1039/D5PM00099H","DOIUrl":"https://doi.org/10.1039/D5PM00099H","url":null,"abstract":"&lt;p &gt;Imatinib is currently considered the “gold standard” pharmacotherapy for chronic myelogenous leukemia (CML) at all stages and is most commonly used in the form of tablets taken orally. The aim of the present study was to perform a quality assessment, bioequivalence study, and safety and tolerability assessment of an investigational test product, imatinib tablets (400 mg), and its comparability with a reference product (Glivec tablets, 400 mg). &lt;em&gt;In vitro&lt;/em&gt; dissolution studies of the test and reference products were conducted in three different buffer media (pH 1.2, pH 4.5, and pH 6.8) using Apparatus II (paddle), and the results were compared. The similarity (&lt;em&gt;f&lt;/em&gt;&lt;small&gt;&lt;sub&gt;2&lt;/sub&gt;&lt;/small&gt;) factor was calculated to assess &lt;em&gt;in vitro&lt;/em&gt; bioequivalence requirements. An open-label, balanced, randomized, two-treatment, two-sequence, two-period, single oral dose, crossover, bioequivalence study was conducted in normal, healthy, adult human subjects under fed conditions. The pharmacokinetic parameters &lt;em&gt;T&lt;/em&gt;&lt;small&gt;&lt;sub&gt;max&lt;/sub&gt;&lt;/small&gt;, &lt;em&gt;C&lt;/em&gt;&lt;small&gt;&lt;sub&gt;max&lt;/sub&gt;&lt;/small&gt;, AUC&lt;small&gt;&lt;sub&gt;0–&lt;em&gt;t&lt;/em&gt;&lt;/sub&gt;&lt;/small&gt;, and AUC&lt;small&gt;&lt;sub&gt;0–∞&lt;/sub&gt;&lt;/small&gt; were calculated through a non-compartmental model using Phoenix WinNonlin Version 8.3 (Certara L.P.) software. Statistical evaluation and comparison of the two formulations were carried out using PROC GLM in SAS version 9.4 (SAS Institute Inc., USA). The safety profile of the investigational product was monitored during the study by applying a clinical process for recording observed untoward effects post-administration of the investigational product. The investigational test product met USP and BP pharmacopoeial quality standards for &lt;em&gt;in vitro&lt;/em&gt; dissolution. Very rapid dissolution (&gt;85% release in 15 minutes) was obtained for the reference and test products in all three buffered dissolution media (pH 1.2, pH 4.5, and pH 6.8) in &lt;em&gt;in vitro&lt;/em&gt; dissolution studies. The dissolution profile of the investigational test product (imatinib tablets, 400 mg) was comparable to that of the reference product (Glivec tablets, 400 mg). Furthermore, pharmacokinetic values (&lt;em&gt;C&lt;/em&gt;&lt;small&gt;&lt;sub&gt;max&lt;/sub&gt;&lt;/small&gt;, &lt;em&gt;T&lt;/em&gt;&lt;small&gt;&lt;sub&gt;max&lt;/sub&gt;&lt;/small&gt;, and AUC) of the test and reference forms of imatinib were similar. Geometric mean ratios (test/reference) for the AUC&lt;small&gt;&lt;sub&gt;0–∞&lt;/sub&gt;&lt;/small&gt;, AUC&lt;small&gt;&lt;sub&gt;0–&lt;em&gt;t&lt;/em&gt;&lt;/sub&gt;&lt;/small&gt;, and &lt;em&gt;C&lt;/em&gt;&lt;small&gt;&lt;sub&gt;max&lt;/sub&gt;&lt;/small&gt; were 95.2, 0.95.2, and 98.4, respectively. Confidence limits for each of these parameters were in the interval (80.00, 125.00), as were the unadjusted confidence limits. The test and reference formulations of imatinib met the criteria for bioequivalence based on the rate and extent of absorption. Based on the findings of this study, it can be concluded that the test product is bioequivalent and safe, thus suggesting the clinical application of the test product as an alternative to Glivec 400 mg film-c","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 807-813"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00099h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624154","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":"Synthesis and preliminary evaluation of cardiac imaging with [68Ga]Ga-NOTA-CTP in normal and infarcted CD1 mice†","authors":"Surendra Reddy Gundam, Manasa Kethamreddy, Andy González Rivera, Aditya Bansal, Viktoria Krol, Daniella A. Sahagun, Joanna E. Kusmirek, Derek R. Johnson, Maliha Zahid, Val J. Lowe and Mukesh K. Pandey","doi":"10.1039/D5PM00047E","DOIUrl":"https://doi.org/10.1039/D5PM00047E","url":null,"abstract":"<p >Cell-penetrating peptide-based probes for positron emission tomography (PET) are currently being developed for cardiac imaging. Herein, we have conjugated a synthetic 12 amino acids (NH<small>₂</small>-APWHLSSQYSRT-COOH) cardiac targeting peptide (CTP) with a NOTA chelator for <small>⁶⁸</small>Ga labeling. The [<small>⁶⁸</small>Ga]Ga-NOTA-CTP was synthesized with a decay-corrected radiochemical yield of 68.9 ± 12.8% (<em>n</em> = 13) and molar activity (<em>A</em><small>_m</small>) of 1.3 ± 0.5 GBq per μmol (<em>n</em> = 13). The tracer was evaluated in healthy and diseased CD1 mice with myocardial infarction following ligation of the left anterior descending artery. PET/CT imaging and <em>ex vivo</em> biodistribution revealed rapid (within 30 min) clearance of [<small>⁶⁸</small>Ga]Ga-NOTA-CTP from the blood through renal and hepatobiliary excretion pathways in both healthy and infarcted animals. The uptake of [<small>⁶⁸</small>Ga]Ga-NOTA-CTP in the heart of healthy and infarcted animals did not show any statistically significant difference for up to 120 min post-injection, but regional differences within healthy and infarcted hearts were detected with [<small>⁶⁸</small>Ga]Ga-NOTA-CTP by PET/CT imaging at early time points post-injection. Within a healthy heart, the left ventricle standardized uptake value (SUV) was lower than the right ventricle SUV at 10–30 min post-injection. This regional difference between the left and right ventricles was absent in the infarcted heart, likely due to post-ligation changes.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 691-702"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00047e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624142","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":"Outstanding Reviewers for RSC Pharmaceutics in 2024","authors":"","doi":"10.1039/D5PM90008E","DOIUrl":"https://doi.org/10.1039/D5PM90008E","url":null,"abstract":"<p >We would like to take this opportunity to thank all of <em>RSC Pharmaceutics</em>’ reviewers for helping to preserve quality and integrity in pharmaceutics literature. We would also like to highlight the Outstanding Reviewers for <em>RSC Pharmaceutics</em> in 2024.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 666-666"},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm90008e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624141","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":"Optimizing mesoporous silica synthesis procedures to enhance their potential as nanoplatforms in therapeutic applications†","authors":"Olia Alijanpourtolouti, Gamini Senanayake, Sulev Koks and David J. Henry","doi":"10.1039/D5PM00066A","DOIUrl":"https://doi.org/10.1039/D5PM00066A","url":null,"abstract":"<p >PARK7 mRNA encodes the DJ-1 protein, which functions as a protective agent against oxidative stress and cell damage within brain cells. Mutations in the mRNA can lead to reduced production of DJ-1 and initiate brain diseases such as Parkinson's disease. Transport of appropriate mRNA to damaged brain cells may provide a suitable treatment. Mesoporous silica nanoparticles (MSNPs), particularly pore-expanded and dye-labeled varieties, are regarded as potential carriers for large therapeutic agents such as mRNA. This study explored the influence of alterations in reaction conditions on the structural characteristics of MSNPs to produce nanoparticles with favorable characteristics for delivering large therapeutic agents to target sites. One-stage and two-stage procedures were compared for the introduction of 3-aminopropyltriethoxysilane (APTES) and an APTES−dye adduct, in conjunction with two different surfactants, cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC). Analysis of the MSNPs shows that the two-stage method using CTAB as a surfactant produced amine-functionalized, dye-labelled particles with smaller overall size and better uniformity than the one-stage approach. However, due to their small pore size (&lt;10 nm), these particles were unable to encapsulate the PARK7 mRNA (926 nucleotides). The one-stage method <em>via</em> CTAC produced MSNPs with a large pore size (150 nm), broad pore distribution (10–20 nm), and high aggregation, limiting their suitability for brain-targeted gene delivery. In comparison, the two-stage method using CTAC yielded well-ordered MSNPs with an optimal size (80 nm) and pore diameters (15–20 nm), enabling effective encapsulation of the large PARK7 mRNA and offering strong potential for future brain gene therapy studies.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 792-806"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00066a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624153","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 physicochemical, biophysical, and in vitro 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 and Heidi M. Mansour","doi":"10.1039/D4PM00265B","DOIUrl":"10.1039/D4PM00265B","url":null,"abstract":"<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 <em>P</em> 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. <em>In vitro</em> studies showed high cell viability (&gt;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":" 4","pages":" 731-748"},"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":"Calcium phosphate reinforced chitosan–carrageenan scaffolds: characterization and in vitro assessment for wound healing†","authors":"Vinita Patole, Gaurav Kavitkar, Ganesh Ingavle, Isha Behere, Ravindra Wavhale, Abhishek Jha, Sanjeevani Deshkar, Avinash Sanap and Pramod Sakpal","doi":"10.1039/D4PM00284A","DOIUrl":"https://doi.org/10.1039/D4PM00284A","url":null,"abstract":"<p >Wound healing is a multifaceted and dynamic biological process, which traditional wound dressings often fail to adequately support, leading to prolonged healing times. It would be highly beneficial to develop wound dressings with the ability to support biological processes such as cell proliferation and angiogenesis and deliver the active agents required to restore intracellular activities to promote wound healing. The current work aimed at developing a polyelectrolyte complex of chitosan (CH) and an anionic polymer, condensed with calcium phosphate (CaP) powder to attain antibacterial and angiogenic potential, cell proliferation, appropriate swelling index, and enhanced wound healing. Polyelectrolyte complexes (PECs) were formulated using chitosan (CH), as a cationic polymer and pectin (PE), sodium alginate (SA), and carrageenan (CA), respectively, as an anionic polymer through a lyophilization process. PEC formation was confirmed by FTIR, XRD, and DSC by observing the changes in their vibrational frequencies, structures, and thermal properties. SEM revealed the porous structure of the scaffolds. From the prepared PEC scaffolds, chitosan–carrageenan (CH-CA) was selected for further studies based on the swelling index, porosity, and degradation studies. Following the production of CaP powder using a microwave-assisted synthesis method, the powder was characterized by FTIR, SEM, XRD, and energy dispersive X-ray (EDX) techniques before being loaded onto CH-CA scaffolds. The results demonstrated approximately 60.75% release of calcium ions (Ca<small>⁺⁺</small>) from the CH-CA scaffolds in PBS, pH 5.5, as analysed by atomic absorption spectroscopy (AAS) over 24 h. The scaffolds demonstrated a higher swelling index and exhibited antimicrobial activity against <em>E. coli</em> and <em>S. aureus</em>. The scaffolds were found to be hemocompatible and demonstrated angiogenic potential, evidenced by stimulating new blood vessel development in a chick yolk sac membrane assay. Cell proliferation studies demonstrated the cytocompatibility of the scaffolds, and improvement in the cell density of the L929 mouse fibroblast cell line was observed in a live/dead assay. In conclusion, the calcium-loaded CH-CA scaffolds demonstrated antimicrobial properties, increased angiogenesis, blood compatibility, and cell proliferation, indicating their potential as an appropriate wound dressing material.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 772-791"},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00284a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624152","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}