Pharmaceutics最新文献

{"title":"UHPLC-MS/MS Method for the Simultaneous Quantification of 12 Antiretroviral Drugs in Human Plasma Using Dried Sample Spot Devices: Development, Validation, and Stability Evaluation.","authors":"Sara Soloperto, Elisa Martina, Alice Palermiti, Elisa Barnini, Greta Sabbia, Gianluca Bianco, Martina Billi, Camilla Martino, Alessandra Manca, Marco Simiele, Jessica Cusato, Antonio D'Avolio, Amedeo De Nicolò","doi":"10.3390/pharmaceutics18040513","DOIUrl":"10.3390/pharmaceutics18040513","url":null,"abstract":"<p><p><b>Background/Objectives</b>: In several contexts, Dried Sample Spot Devices (DSSDs) offer a convenient and safe alternative for sampling, storage, and shipment, allowing the transport and storage of biological samples at room temperature, reducing shipment costs and improving access to diagnostics in faraway sites. This can be pivotal for the use of the therapeutic drug monitoring of anti-HIV treatment: therefore, this study aimed to develop and validate a UHPLC-MS/MS method for the simultaneous quantification of 12 antiretroviral drugs, including the recently introduced long-acting agents, in Dry Plasma Spots (DPSs). <b>Methods</b>: First, 100 µL of plasma sample and 100 µL of internal standard solution were spotted on each DSSD. After complete drying, DPSs were added with an acidifying solution (ammonium acetate buffer pH 4), and then, each sample underwent extraction with hexane-dichloromethane 50:50 (<i>v</i>/<i>v</i>). After tumbling, the organic phase was evaporated and reconstituted for injection. An Acquity UPLC HSS T3 1.8 µm, 2.1 × 150 mm column at 50 °C enabled separation, performed using H₂O + F.A. 0.05% (phase A) and ACN + F.A. 0.05% (phase B) as the mobile phase in gradient elution mode, for a total run time of 15 min. <b>Results:</b> The method was validated over the clinically relevant concentration ranges. For all quality control levels, accuracies ranged from 98.2% to 114.1%, and intra-day and inter-day RSD values ranged from 2.7% to 9.7% and 5.2% to 13.9%, respectively. All analytes demonstrated satisfactory short- and long-term stability in DPSs, confirming the suitability of shipment and storage at room temperature. <b>Conclusions</b>: The method demonstrated robustness and reproducibility in accordance with FDA and EMA guidelines. It ensures satisfactory accuracy and rapid analysis, supporting its application in clinical practice, including for monitoring the newest long-acting drugs.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Fahmy et al. PEGylated Chitosan Nanoparticles Encapsulating Ascorbic Acid and Oxaliplatin Exhibit Dramatic Apoptotic Effects against Breast Cancer Cells. <i>Pharmaceutics</i> 2022, <i>14</i>, 407.","authors":"Sherif Ashraf Fahmy, Asmaa Ramzy, Asmaa A Mandour, Soad Nasr, Anwar Abdelnaser, Udo Bakowsky, Hassan Mohamed El-Said Azzazy","doi":"10.3390/pharmaceutics18040511","DOIUrl":"10.3390/pharmaceutics18040511","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium Stearate-Assisted Optimization of a Cannabidiol Dry Powder Inhaler for Enhanced Dissolution and Aerosol Performance.","authors":"Jin-Hyuk Jeong, Jae Seok Jeong, Hyeon-Seo Moon, Jae Woon Son, Kyung Hyun Min, Dong-Wook Kim, Chang-Soo Han, Wonwoong Lee, Chun-Woong Park, Ji-Hyun Kang","doi":"10.3390/pharmaceutics18040512","DOIUrl":"10.3390/pharmaceutics18040512","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Cannabidiol (CBD) has emerged as a potential therapeutic agent for respiratory disorders, including asthma and chronic obstructive pulmonary disease. However, its clinical translation via pulmonary delivery is limited by poor aqueous solubility, chemical instability, and low local bioavailability. This study aimed to develop and optimize a sodium stearate (NaSt)-based spray-dried dry powder inhaler (DPI) formulation to enhance the aerosol performance, dissolution, and storage stability of CBD. <b>Methods</b>: CBD microparticles were prepared by spray drying using NaSt as the primary excipient. The feed preparation method, spray-drying parameters, and CBD:NaSt ratios were systematically optimized. The resulting powders were evaluated for aerodynamic properties using cascade impaction, dissolution behavior in simulated lung fluid, solid-state characteristics, and accelerated stability under stress conditions. <b>Results</b>: The optimized formulation, SD-4, a spray-dried CBD:NaSt formulation prepared at a 20:80 weight ratio using Process B, demonstrated excellent aerosolization performance, with a fine particle fraction (FPF) exceeding 50% and a mass median aerodynamic diameter (MMAD) of 5.08 ± 0.1 μm. Dissolution testing revealed more than a three-fold increase in drug release compared with raw CBD, attributed to amorphous dispersion within the NaSt matrix and surfactant-induced micellization. Accelerated stability studies confirmed improved retention of the amorphous state and drug content, while antioxidant incorporation further reduced oxidative degradation. <b>Conclusions</b>: The NaSt-based spray-dried formulation significantly improved aerosol deposition efficiency, dissolution rate, and physicochemical stability of CBD. This formulation strategy may provide a promising platform for pulmonary delivery of poorly water-soluble compounds.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Mechanisms and Key Influencing Factors of Paclitaxel and Indocyanine Green Co-Loading in Lipid Nanoparticles.","authors":"Weishen Zhong, Kai Yue, Genpei Zhang, Ziyang Hu","doi":"10.3390/pharmaceutics18040505","DOIUrl":"10.3390/pharmaceutics18040505","url":null,"abstract":"<p><p><b>Background:</b> The reliable co-loading of paclitaxel (PTX) and indocyanine green (ICG) into a single lipid nanoparticle (LNP) enables synergistic antitumor delivery but remains challenging due to their distinct physicochemical properties. <b>Methods:</b> This study integrated COSMO-RS calculations, molecular dynamics simulations, and in vitro assays to systematically investigate the effects of lipid composition, drug modification, particle size, and solvent environment on dual-drug loading. <b>Results:</b> This work indicate that DMPS lipid membranes featuring highly polar headgroups and ordered bilayer structures stably bind both ICG and PTX, achieving drug-loading efficiencies (DLEs) of 7.2% and 5.6%, respectively. Carboxylation of PTX enhanced hydrogen bonding with DMPS, while alkyl chain modifications improved membrane insertion, though excessive chain length (e.g., C12) reduced stability due to increased flexibility. Increasing the LNP size from 50 nm to 250 nm raised the DLE of PTX from 4.7% to 8.1%, while sizes beyond 500 nm led to membrane destabilization. The use of 20 vol% ethanol increased total drug loading by 51% by disrupting the hydration shell of ICG and suppressing PTX aggregation; however, ethanol concentrations exceeding 40 vol% intensified drug-solvent competition and weakened membrane binding. <b>Conclusions:</b> This study provides a comprehensive elucidation of the multifactorial regulatory mechanisms underlying dual-drug loading in LNPs, offering a theoretical basis for the rational design of efficient co-delivery systems.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Species-Specific Susceptibility of Planktonic and Biofilm Forming Candida Strains to Cyclodextrin-Encapsulated Essential Oils.","authors":"Sourav Das, Farid Baradarbarjastehbaf, Aliz Sára Szokolics, Génesis Katherine Dela Campos, Zoltán Gazdag, Aleksandar Széchenyi, Attila Miseta, Gábor L Kovács, Tamás Kőszegi","doi":"10.3390/pharmaceutics18040508","DOIUrl":"10.3390/pharmaceutics18040508","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Essential oils (EOs) have multi-target antifungal activity, but their translation is limited by volatility and poor aqueous dispersibility. Randomly methylated β-cyclodextrin (RAMEB) inclusion may enhance effective exposure and thereby alter susceptibility, stress responses, and biofilm outcomes in a species-dependent manner. This study quantified species-specific planktonic and biofilm susceptibility to four EOs and their RAMEB complexes across clinically relevant Candida species. <b>Methods:</b> Lavender (L), lemon balm (B), peppermint (P), and thyme (T) oils and their RAMEB complexes (RL, RB, RP, and RT) were tested against <i>C. albicans</i> and non-albicans Candida. Susceptibility thresholds were used to derive phase plasticity metrics. Functional inhibition was assessed via planktonic metabolism/viability and established biofilm metabolism/viability/biomass. Mechanistic signatures were captured by ROS/RNS measurements and a qPCR analysis of antioxidant genes (<i>CAT1</i>, <i>GPX1</i>, and <i>SOD1</i>) was performed. Mixed-effects models and multivariate/unsupervised and interpretable classification approaches (k-means, PCA, and CRT) were used to integrate endpoints and stratify response phenotypes. <b>Results:</b> Susceptibility thresholds were strongly species-structured (lowest MIC₉₀/EC₁₀ for <i>C. albicans</i>; higher thresholds and broader sublethal windows in non-albicans species). RAMEB complexation produced formulation-dependent shifts in efficacy, with RT emerging as the most consistent broad-spectrum inhibitory condition across compartments. Biofilm biomass was comparatively insensitive even when viability was suppressed, indicating a decoupling of structural biomass from biocidal activity. Mechanistic signatures were broadly conserved across species and linked to antioxidant-program engagement, with <i>CAT1</i>-related rules contributing to responder/tolerant classification. <b>Conclusions:</b> Integrating MIC/EC plasticity with functional and mechanistic markers supports the rational selection of EO formulations; RAMEB complexation, particularly RT, prioritizes candidates for further pharmaceutical optimization while highlighting species-specific vulnerabilities.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fire in an Icy Desert: Oncolytic Virotherapy for Pancreatic Adenocarcinoma.","authors":"Alessandra Rossetto, Alberto Reale","doi":"10.3390/pharmaceutics18040510","DOIUrl":"10.3390/pharmaceutics18040510","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, characterized by early metastasis, dense desmoplastic stroma and a profoundly immunosuppressive, lymphocyte-depleted tumor microenvironment that severely limits the efficacy of current systemic and immunotherapeutic approaches. Oncolytic viruses (OVs), which selectively replicate in and lyse malignant cells while activating antitumor immunity, have emerged as attractive candidates to convert this \"cold\" tumor into a more inflamed and therapeutically responsive disease. In this review, we summarize clinical evidence on the main OV platforms evaluated in PDAC, including adenovirus, herpes simplex virus, vaccinia virus, parvovirus and reovirus, with a focus on clinical trials. Across these classes of viruses, intratumoral administration has consistently proven feasible and generally well tolerated, with frequent evidence of viral replication, microenvironmental remodeling and immune activation, but only modest and often transient antitumor responses in small, early-phase cohorts. We then discuss key biological and translational challenges that currently limit OV impact in PDAC, such as systemic delivery in the context of pre-existing antiviral immunity and rapid clearance, penetration through the fibrotic stroma, and rational selection of encoded transgenes to reshape myeloid cell-driven, pro-tumoral inflammation and enhance T-cell recruitment. Finally, we outline future directions for the field, including carrier-cell-based systemic delivery, stroma-targeting or cytokine-armed constructs, and combinatorial strategies with chemotherapy and immune checkpoint blockade, arguing that design refinement, innovative combinations and mechanism-driven trial designs will be essential to unlock the full therapeutic potential of oncolytic virotherapy in PDAC.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidic Fabrication of Alendronate-Modified Lipid Nanoparticles for Bone-Targeted mRNA Delivery.","authors":"Kangling Xu, Junyu Su, Hailin Ma, Yanxia Zhu","doi":"10.3390/pharmaceutics18040509","DOIUrl":"10.3390/pharmaceutics18040509","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Bone-targeted drug delivery systems hold great promise for treating skeletal diseases, yet the optimal strategy for functionalizing lipid nanoparticles (LNPs) with bone-homing ligands remains insufficiently explored. Herein, we compared two alendronate sodium (Alen) modification approaches (pre-conjugation and post-conjugation) for constructing bone-targeted LNPs capable of delivering mRNA to skeletal tissues. <b>Methods:</b> LNPs were fabricated via microfluidic mixing, and the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-alendronate conjugate (DSPE-PEG-Alen) required for the pre-conjugation method was synthesized. The bone-targeting ability of LNPs prepared by the two Alen modification strategies was evaluated using an <i>in vitro</i> hydroxyapatite (HAP) binding assay. Furthermore, the physicochemical properties, bone-targeting performance, mRNA delivery efficiency, and biosafety of the LNPs prepared by the post-conjugation method were assessed through cellular uptake, <i>in vivo</i> imaging, and other methods. <b>Results:</b> Hydroxyapatite binding assays revealed that the post-conjugation strategy afforded significantly superior bone affinity compared to the pre-conjugation approach. In addition, ex vivo bone fragment binding experiments further confirmed that the bone-targeting LNPs prepared by the post-conjugation method exhibited stronger bone-binding capability compared to unmodified LNPs. The optimized Alen-LNPs demonstrated efficient cellular uptake and functional mRNA translation in bone marrow mesenchymal stem cells with negligible cytotoxicity. <i>In vivo</i> studies in mice confirmed the preferential accumulation of Alen-LNPs in bone tissues, with successful green fluorescent protein (GFP) mRNA translation detected in bone tissue sections. Histopathological analysis confirmed the biosafety of the formulation. <b>Conclusions:</b> This study establishes the post-conjugation strategy as the superior approach for Alen functionalization of LNPs, providing a robust and reproducible platform for bone-targeted mRNA therapeutics.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvements of Blood Compatibility, Drug-in-Polymer Coating Stability and Prevention of Crack Formation: Application to Drug-Eluting Stents.","authors":"Tarek M Bedair, Dong Keun Han","doi":"10.3390/pharmaceutics18040506","DOIUrl":"10.3390/pharmaceutics18040506","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Commercially available drug-eluting stents still suffer from poor blood compatibility, polymer coating delamination, polymer cracking and lack of stability during and after stent implantation that led to adverse events such as stent thrombosis and in-stent restenosis. This article highlights the advantages of using silicon nanofilament (SiNf) as an interface between stent surface and drug-in-polymer coating or bloodstream. <b>Methods</b>: Thin layer of SiNf was successfully formed on the surface of Co-Cr substrate via one-step simple method. For stent applications, sirolimus-in-poly(D,L-lactide) (PDLLA/SRL) matrix was coated on control and SiNf-modified Co-Cr substrates and the stability, cracking, and long-term degradation was compared. Blood compatibility studies were also compared between control and SiNf-modified Co-Cr substrates. <b>Results</b>: The morphology of the filaments showed nanosized structures with nano-gaps between the filaments which support mechanical interlocking of PDLLA/SRL coating and enhanced the coating stability with no coating delamination whereas, the control substrate presented 97% of coating delamination. The PDLLA/SRL coating on stent platform demonstrates smooth and uniform morphology without webbing between stent struts. After stent ballooning, the control stent presented cracking and peeling of the polymer coating from the surface whereas, the SiNf-modified stent did not show any signs of these unfavorable defects. Moreover, SiNf-modified surface showed reduced fibrinogen adsorption and lower number of platelet adhesion with round shape morphology. <b>Conclusions</b>: Overall, this suggests that modifying the metallic substrates with SiNf could act as a universal coating for reinforcing the polymer coating stability, prevent coating defects that accompany stent ballooning, and improve the blood compatibility of the material surfaces that could have various applications to medical implants and devices.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coaxial Jet Mixing for Pharmaceutical Nanocarrier Production: Experimental Analysis and Mechanistic Modeling.","authors":"Diego Caccavo, Raffaella De Piano, Francesca Landi, Gaetano Lamberti, Anna Angela Barba","doi":"10.3390/pharmaceutics18040507","DOIUrl":"10.3390/pharmaceutics18040507","url":null,"abstract":"<p><p><b>Background/Objectives:</b> This study addresses the need for scalable and predictive strategies linking mixing conditions to nanocarrier properties by developing and analyzing a coaxial jet antisolvent process for the continuous production of pharmaceutical nanocarriers. <b>Methods:</b> A single experimental platform was used to generate both curcumin-based nanoparticles and nanoliposomes, enabling direct comparison of how mixing regime and formulation variables influence product characteristics. <b>Results:</b> Fluid-dynamic behavior was first characterized using tracer and micromixing experiments, revealing a strong dependence of mixing time on flow conditions, with characteristic mixing times decreasing from >1000 ms under laminar conditions to approximately 10-30 ms in turbulent regimes. Nanoparticles and liposomes obtained under optimized conditions exhibited mean sizes in the range of 120-250 nm, with polydispersity indices typically below 0.2 under optimized turbulent conditions. To rationalize these observations, a computational framework was implemented, combining Reynolds-averaged computational fluid dynamics with a population balance formulation solved by the method of moments. The model provided spatially resolved insight into solvent exchange, supersaturation development, and nucleation-growth dynamics, showing good agreement with experimental trends and capturing the effect of mixing conditions on particle size across different regimes. <b>Conclusions:</b> Although simplified, the modeling approach establishes the basis for future extensions toward full population-balance distribution simulations capable of predicting complete particle size distributions, highlighting the ability of the coaxial jet mixer to control supersaturation and particle formation through tunable hydrodynamic conditions. This capability makes the system particularly attractive compared to conventional batch or less controllable mixing technologies, enabling a more rational and scalable design of pharmaceutical nanocarriers, with good encapsulation performance as discussed in the main text.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Degradable Nanosystem Based on Small Gold Nanoparticles and Albumin for Amyloid Aggregation Inhibition.","authors":"Matías Levio, Francisco Rossel Carrera, Fredys Sánchez Hoyos, Maycol Huerta, Carlos Alamos, Rodrigo Vásquez-Contreras, Marcelo J Kogan, Eyleen Araya Fuentes","doi":"10.3390/pharmaceutics18040504","DOIUrl":"10.3390/pharmaceutics18040504","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Beta amyloid (Aβ) aggregates play a central role in the pathophysiology of Alzheimer's disease (AD), and their detection and modulation remain major challenges in developing effective therapeutic and diagnostic strategies. Previously, gold nanoparticles with plasmonic and optical properties in the near-infrared (NIR) region and photothermal capabilities have been designed for detecting and disaggregating Aβ aggregates. However, these systems often face limitations related to biodegradability, long-term accumulation, and safety. In this work, a degradable NIR-responsive nanosystem based on small gold nanoparticles (sAuNPs), potentially excretable due to their small size, encapsulated within bovine serum albumin (BSA) and functionalized with the all-D peptide D3, was developed to inhibit Aβ aggregation. <b>Methods</b>: sAuNPs (~5-6 nm), functionalized with HS-PEG-NH₂, were encapsulated into BSA nanoparticles using a desolvation method and subsequently conjugated to D3, resulting in the nanosystem f-sAuNPs-BSANPs-D3. The nanosystem was characterized by UV-Vis-NIR spectroscopy, dynamic light scattering, zeta potential analysis, electron microscopy, and nanoparticle tracking analysis. The effects of the nanosystem on Aβ_1-42 aggregation were evaluated using a thioflavin T assay and electron microscopy. Additionally, the effects of f-sAuNPs-BSANPs-D3 on cell viability and its stability against trypsin digestion were assessed. <b>Results</b>: The nanosystem exhibited a measurable photothermal response under NIR irradiation and significantly reduced fibril formation. It did not affect the viability of SH-SY5Y neuronal cells at the tested concentrations. Trypsin incubation experiments demonstrated that the nanosystem remained stable at low enzyme concentrations mimicking plasma conditions, whereas higher enzyme concentrations induced degradation of the albumin matrix and subsequent disaggregation of sAuNPs. <b>Conclusions</b>: Overall, this study presents a degradable, albumin-based sAuNP nanosystem with NIR-responsive properties and potential for nanomedicine applications to inhibit Aβ aggregation in AD.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}