Molecular Pharmaceutics最新文献

{"title":"ALC-0315 Lipid-Based mRNA LNP Induces Stronger Cellular Immune Responses Postvaccination.","authors":"Zuchen Song, Lan Jin, Lina Jiao, Ruihong Yu, Huina Liu, Shun Zhang, Yaoren Hu, Yuechao Sun, Entao Li, Guofang Zhao, Zhenguang Liu, Ting Cai","doi":"10.1021/acs.molpharmaceut.4c00995","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c00995","url":null,"abstract":"<p><p>At the end of 2019, SARS-CoV-2 emerged and rapidly spread, having a profound negative impact on human health and socioeconomic conditions. In response to this unprecedented global health crisis, significant advancements were made in the mRNA vaccine technology. In this study, we have compared the difference between two SARS-CoV-2 receptor-binding domain (RBD) mRNA-Lipid nanoparticle (LNP) vaccines prepared from two different ionizable cationic lipids: ALC-0315 and MC3. Characterization of RBD mRNA-LNPs showed that both MC3-LNP and ALC-0315-LNP are highly uniform and stable. Furthermore, we assessed the humoral immune response in mice after immunization; our findings indicated that both vaccine formulations effectively enhanced the formation and differentiation of germinal center (GC). Notably, the mice immunized with the ALC-0315-LNP vaccine elicited higher levels of IgG and its subclasses and significantly enhanced the activation of dendritic cells and T cells in draining lymph nodes (dLNs) compared to those immunized with the MC3-LNP vaccine. Further analysis of the T cell phenotype after splenic restimulation showed that mice injected with both LNP mRNA vaccines had significantly increased activation of the splenic T cells and Th1-type cytokine production. In addition, our finding showed that both LNP mRNA vaccines significantly increased the proportions of follicular helper T cells (Tfh) and long-lasting plasma cells in the dLNs of mice on day 14 postimmunization compared to control. In conclusion, both ALC-0315 and MC3 exhibited good stability and immunogenicity as mRNA-LNP recipes, but the ALC-0315-based mRNA-LNP vaccine showed higher efficacy in humoral and cellular immune responses compared to MC3.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulation of Antral Conditions for Estimating Drug Apparent Equilibrium Solubility after a High-Calorie, High-Fat Meal.","authors":"Christos Reppas, Christina Chorianopoulou, Ioanna Karkaletsi, Shirin Dietrich, Andriani Bakolia, Maria Vertzoni","doi":"10.1021/acs.molpharmaceut.4c01038","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01038","url":null,"abstract":"<p><p>The simulation of antral conditions for estimating drug apparent equilibrium solubility after a high-calorie, high-fat meal is challenging. In this study, (1) we measured the apparent equilibrium solubility of two model lipophilic drugs, ketoconazole and danazol, in antral aspirates collected at various time points after a minced high-calorie, high-fat meal and a glass of water 30 min after initiation of meal administration, and we designated one point estimate for ketoconazole and one point estimate for danazol; (2) we evaluated the usefulness of FeSSGF-V2 and FEDGAS pH = 3 in reproducing the two point estimates; (3) we evaluated potential compositions of FeSSGF-V3 that simulate the pH, the buffer capacity toward both less acidic and more acidic values, and the antral lipid and protein contents with easily accessible, commercially available products, and (4) we identified the most useful composition of FeSSGF-V3 for reproducing the two point estimates. For both model drugs, apparent solubility in FeSSGF-V2 and in FEDGAS pH 3 deviated substantially from the corresponding point estimate. For FeSSGF-V3, hydrochloric acid, acetates, and FEDGASbuffer pH 3 were evaluated for regulating the pH and buffer capacity, FEDGASgel was used for simulating the lipid content, and Régilait skimmed milk powder was used for simulating the protein content. Level III FeSSGF-V3 prepared with hydrochloric acid, 6.1% (w/v) Régilait, and 2.83% (w/v) FEDGASgel, i.e., one-sixth of FEDGASgel concentration in FEDGAS pH 3, was comparatively the most useful medium for point estimating ketoconazole and danazol apparent solubility in antral contents after water administration in the fed state, induced as requested by regulatory authorities in oral drug bioavailability studies. Level III FeSSGF-V3 prepared by using hydrochloric acid as the principal pH controlling species could be useful in the evaluation of food effects on drug absorption with <i>in silico</i> physiologically based biopharmaceutics modeling approaches and, also, with biorelevant in vitro methodologies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring Design of Microneedles for Drug Delivery and Biosensing.","authors":"Yuexi Lin, Muamer Dervisevic, Hao Zhe Yoh, Keying Guo, Nicolas H Voelcker","doi":"10.1021/acs.molpharmaceut.4c01266","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01266","url":null,"abstract":"<p><p>Microneedles (MNs) are emerging as versatile tools for both therapeutic drug delivery and diagnostic monitoring. Unlike hypodermic needles, MNs achieve these applications with minimal or no pain and customizable designs, making them suitable for personalized medicine. Understanding the key design parameters and the challenges during contact with biofluids is crucial to optimizing their use across applications. This review summarizes the current fabrication techniques and design considerations tailored to meet the distinct requirements for drug delivery and biosensing applications. We further underscore the current state of theranostic MNs that integrate drug delivery and biosensing and propose future directions for advancing MNs toward clinical use.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-Based Multifunctional Nanoliposomes for Enhanced HCC Therapy and Diagnosis.","authors":"Jingxin Sun, Zhehao Jin, Yong Jin, Haidan Yuan, Guangyu Jin, Jishan Quan","doi":"10.1021/acs.molpharmaceut.4c00917","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c00917","url":null,"abstract":"<p><p>The morbidity and mortality rates of hepatocellular carcinoma (HCC) are high and continue to increase. The antitumor effects of single therapies are limited because of tumor heterogeneity and drug resistance, and the lack of real-time monitoring of tumor progression during the treatment process leads to poor therapeutic outcomes. Therefore, novel nanodelivery platforms combining tumor therapy and diagnosis have garnered extensive attention. In this study, we developed a multifunctional nanodelivery vector, LPSD-DOX/siRNA, which was loaded with oleic acid-modified superparamagnetic iron oxide nanoparticles (OA-SPION) and the antitumor drug doxorubicin (DOX), further modified by DOTAP to carry small interfering RNA targeting phosphatidylinositol proteoglycan-3 (Glypican-3, GPC3) (siRNA-GPC3). These components were utilized for the combined treatment of HCC and tumor monitoring with magnetic resonance imaging. LPSD-DOX/siRNA exhibited high drug loading, high gene transfection efficiency, and low toxicity. Pharmacokinetic and in vivo distribution experiments showed that LPSD-DOX/siRNA significantly prolonged the circulation time of DOX and enhanced drug accumulation at the tumor site. Magnetic resonance imaging demonstrated that LPSD-DOX/siRNA can serve as a T2 imaging contrast agent to enhance the imaging contrast between the tumor site and other tissues and facilitate the imaging monitoring of tumor tissues. Antitumor experiments revealed that the effects of DOX were promoted by inhibiting the expression of GPC3 protein in HepG2 cell-transplanted tumors, with increased tumor apoptosis. In conclusion, LPSD-DOX/siRNA serves as a promising strategy for combination therapy and monitoring of HCC, with significant potential in antitumor therapy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bifunctional Peptide with Penetration Ability for Treating Retinal Angiogenesis via Eye Drops.","authors":"Jing Liao, Lin Zhao, Hongyuan Chen, Chunqian Zhao, Shang Chen, Xiuli Guo, Fengshan Wang, Xiaoxue Liu, Xinke Zhang","doi":"10.1021/acs.molpharmaceut.4c00683","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c00683","url":null,"abstract":"<p><p>Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases. RP7 is an NRP-1 targeting peptide that blocks vascular endothelial growth factor receptor-2 (VEGFR-2) signaling and inhibits angiogenesis, while Tat facilitates the delivery of various cargoes across biological barriers, such as the blood-retina barrier. By combining these attributes, Tat-C-RP7 is anticipated to traverse ocular barriers via ocular topical administration and exert its antiangiogenic effects in the ocular posterior segment. Experimental results demonstrated that Tat-C-RP7 significantly inhibited the proliferation and migration of rat retinal microvascular endothelial cells and effectively reduced tubule formation <i>in vitro</i>. Its antiangiogenic activity was confirmed in zebrafish. The outstanding penetrative capabilities of FITC-labeled Tat-C-RP7 have been validated through cell uptake assays, <i>in vitro</i> cell barrier models, <i>ex-vivo</i> ocular tissues, and <i>in vivo</i> studies. Besides, the half-life of Tat-C-RP7 was longer than that of RP7. In an oxygen-induced retinopathy model, Tat-C-RP7 was shown to reduce the area of angiogenesis following ocular administration. Additionally, it produced no irritating effects on the eyes of rabbits. Overall, Tat-C-RP7 demonstrates excellent ocular penetrability and antiangiogenic effects and represents a promising therapeutic option for treating retinal neovascularization diseases.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Water Activity as an Indicator for Antibody Storage Stability in Lyophilized Formulations.","authors":"Maximilian Zäh, Christoph Brandenbusch, Sebastian Groël, Gerhard Winter, Gabriele Sadowski","doi":"10.1021/acs.molpharmaceut.4c01106","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01106","url":null,"abstract":"<p><p>Lyophilization remains a key method for preserving sensitive biopharmaceuticals such as monoclonal antibodies. Traditionally, stabilization mechanisms have been explained by vitrification, which minimizes molecular mobility in the lyophilized cake, and water replacement, which restores molecular interactions disrupted by water removal. This study proposes a novel design strategy that combines water activity and glass-transition temperature as the main indicators to predict long-term stability in lyophilized formulations. The water activity, calculated as the product of water activity coefficient and (residual) water content, serves as a mutual indicator of molecular interactions and influence of residual water content in the lyophilizate. By predicting beneficial excipient combinations through activity coefficient calculations using the perturbed-chain statistical association fluid theory model and calculating <i>T</i>_g using the Gordon-Taylor equation, the study identifies favorable excipient systems, such as sucrose/ectoine mixtures, providing formulation windows that offer broad stability ranges. The approach was validated with stability studies, confirming that formulations within a water activity range of 0.025-0.25 exhibit high (long-term) stability. This work advances formulation development by integrating water-excipient interactions and residual moisture content into a predictive model, moving beyond traditional empirical methods and offering a robust pathway to the design of stable biopharmaceutical formulations. This makes it possible to achieve high/favorable water activities despite low residual moisture (thus, high glass-transition temperatures) with plausible excipient concentrations and combinations.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Pluronic-Based Micelles from Palm Oil Bioactive Compounds Incorporated by a Dissolvable Microarray Patch to Enhance the Efficacy of Atopic Dermatitis Therapy.","authors":"Khusnul Humayatul Jannah, Christopher Kosasi Ko, Felicia Virginia Thios, Jihan Nabilah Isma, Anugerah Yaumil Ramadhani Aziz, Andi Dian Permana","doi":"10.1021/acs.molpharmaceut.4c00990","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c00990","url":null,"abstract":"<p><p>The high content of vitamin E, including tocopherols and tocotrienols (TCF-TTE), in palm oil (<i>Elaeis guineensis</i>) has made it a promising candidate for the alternative treatment of atopic dermatitis (AD). However, the limited solubility of TCF-TTE has restricted its therapeutic efficacy. In this study, pluronic-based micelles (MCs) encapsulating palm oil-derived TCF-TTE were formulated with dissolvable microarray patch-micelles (DMP-MC) using carboxymethyl cellulose (CMC) synthesized from empty fruit bunches of palm to optimize its delivery for AD. The MC was prepared using a direct dissolution method using Pluronic F68 and F127. The results showed that MC increased the solubility of TCF-TTE, which was further confirmed by an <i>in vitro</i> study where 90.23 ± 2.07% TCF and 4.56 ± 1.36% TTE were released compared to the unencapsulated TCF-TTE extract. Furthermore, CMC biopolymers and MC integrated into DMP-MC with polyvinylpyrrolidone (PVP) exhibited favorable physical properties, such as mechanical strength and penetration ability. DMP-MC also exhibited a better platform with lower permeation, indicating higher retention and increased localized effects on AD skin than cream-MC. Additionally, dermatokinetic profile parameters showed significant improvement. The mean residence time (MRT) parameter indicated that TCF-TTE was retained for longer times 19.28 ± 0.02 h and 20.68 ± 0.01 h. Moreover, an <i>in vivo</i> study revealed that DMP-MC could relieve AD symptoms more rapidly than oral doses and cream-MC, indicating that DMP-MC proved to be more efficient. Furthermore, DMP-MC showed no tissue destruction (granulation and fibrosis) in rats treated with DMP-MC on the seventh day. Therefore, this study successfully developed the MC formula in DMP-MC formulation using synthesized CMC, which could potentially improve AD's therapeutic efficacy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle Association with Brain Cells Is Augmented by Protein Coronas Formed in Cerebrospinal Fluid.","authors":"Claire Rennie, Nabila Morshed, Matthew Faria, Lyndsey Collins-Praino, Andrew Care","doi":"10.1021/acs.molpharmaceut.4c01179","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01179","url":null,"abstract":"<p><p>Neuronanomedicine harnesses nanoparticle technology for the treatment of neurological disorders. An unavoidable consequence of nanoparticle delivery to biological systems is the formation of a protein corona on the nanoparticle surface. Despite the well-established influence of the protein corona on nanoparticle behavior and fate, as well as FDA approval of neuro-targeted nanotherapeutics, the effect of a physiologically relevant protein corona on nanoparticle-brain cell interactions is insufficiently explored. Indeed, less than 1% of protein corona studies have investigated protein coronas formed in cerebrospinal fluid (CSF), the fluid surrounding the brain. Herein, we utilize two clinically relevant polymeric nanoparticles (PLGA and PLGA-PEG) to evaluate the formation of serum and CSF protein coronas. LC-MS analysis revealed distinct protein compositions, with selective enrichment/depletion profiles. Enhanced association of CSF precoated particles with brain cells demonstrates the importance of selecting physiologically relevant biological fluids to more accurately study protein corona formation and subsequent nanoparticle-cell interactions, paving the way for improved nanoparticle engineering for in vivo applications.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Property Optimization: Design, Synthesis, and Characterization of Novel Pharmaceutical Salts and Cocrystal-Salt of Lumefantrine.","authors":"Bolaji C Dayo Owoyemi, Matthias Zeller, Brenda Pereira da Silva, Amos O Akinyemi, Romulo A Ando, Gabriel L Barros de Araujo, Stephen R Byrn","doi":"10.1021/acs.molpharmaceut.4c01244","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01244","url":null,"abstract":"<p><p>Lumefantrine (LMF) is a low-solubility antimalarial drug that cures acute, uncomplicated malaria. It exerts its pharmacological effects against erythrocytic stages of <i>Plasmodium</i> spp. and prevents malaria pathogens from producing nucleic acid and protein, thereby eliminating the parasites. Modifying the structure of a drug through the formation of a pharmaceutical cocrystal or salt presents an avenue through which its physicochemical properties can be optimized. In this work, we report the design/synthesis and solid-state characterization of four new salts and cocrystal-salt forms of LMF; an LMF-ADP salt, monoclinic space group P2₁/n; an LMF-FUM cocrystal-salt, monoclinic space group P2₁/c; an LMF-TAR solvate salt, monoclinic space group P2₁/n; and an LMF-SUC salt, triclinic, space group P1̅ (ADP, dianion of adipic acid; FUM, monoanion of fumaric acid; TAR, dianion of tartaric acid; SUC, dianion of succinic acid). These salts can be obtained by solution as well as by mechanochemical cocrystallization methods. The multicomponent systems gain their stability from hydrogen and partial ionic bonding interactions (N-H···O, O-H···O, N⁺-H···O^-, and O-H⁺···O^-) originating from both the dibutyl ammonium (N⁺-H) site and the alcohol hydroxyl (-OH) site of LMF toward the carboxylate (-C(O^-)═O) functional groups of the coformer anions. SCXRD indicates for LMF-ADP, LMF-TAR, and LMF-SUC complete transfer of all carboxylic acid protons (H⁺) toward the LMF nitrogen, while for LMF-FUM, one of the protons is transferred (leaving a hydrofumarate monoanion). Using salicylic and acetylsalicylic acids as coformers yielded coamorphous solids. Solid-state characterization using powder X-ray diffraction (XRD) and thermal techniques (DSC and TGA) support and confirm the structures obtained from single-crystal XRD. LMF-ADP and LMF-FUM present superior stability under standard conditions (40 ± 2 °C, 75 ± 5% RH, and 3 months) compared to the amorphous samples and the other two salts. LMF-SUC showed poor thermal stability by DSC/TGA, and powder XRD patterns for LMF-TAR showed substantial change after the 3-month stability test. Finally, the calculated equilibrium solubilities for the cocrystal salts indicate an increase of more than twofold compared to LMF's solubility.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biocompatibility of Phosphorus Dendrimers and Their Antibacterial Properties as Potential Agents for Supporting Wound Healing.","authors":"Beata Bielska, Natalia Wrońska, Joanna Kołodziejczyk-Czepas, Serge Mignani, Jean-Pierre Majoral, Iveta Waczulikova, Katarzyna Lisowska, Maria Bryszewska, Katarzyna Miłowska","doi":"10.1021/acs.molpharmaceut.4c01156","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01156","url":null,"abstract":"<p><p>Dendrimers are a wide range of nanoparticles with desirable properties that can be used in many areas of medicine. However, little is known about their potential use in wound healing. This study examined the properties of phosphorus dendrimers that were built on a cyclotriphosphazene core and pyrrolidinium (DPP) or piperidinium (DPH) terminated groups, to be used as potential factors that support wound healing (<i>in vitro</i>). Therefore, the degree of toxicity of the tested compounds for human erythrocytes and the human fibroblast cell line (BJ) was determined, and it was found that at low concentrations, the tested compounds are compatible with blood. The influence of phosphorus dendrimers on plasma proteins (human serum albumin (HSA) and fibrinogen) was examined, with a lack of conformational changes in the structure of these proteins, suggesting that their physiological function was not disturbed. The effects on plasma coagulation cascade and fibrinolysis were also assessed, and it was found that phosphorus dendrimers in low concentrations are blood compatible and interfere neither with coagulation processes nor in clot breakdown. Skin injuries, especially chronic wounds, are also susceptible to infection; therefore, the antimicrobial potential of dendrimers was tested, and it was found that these dendrimers had antibacterial activity against both Gram-negative and Gram-positive bacteria. The highest activity of the tested compounds was found for higher applied concentrations.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}