Drug Delivery and Translational Research最新文献

{"title":"Engineering long-acting injectable in situ forming implants for sustained delivery of citalopram in depression management.","authors":"Haripriya Koppisetti, Deepa Nakmode, Weranga Rajapaksha, Baljinder Singh, Souha Youssef, Yunmei Song, Sanjay Garg","doi":"10.1007/s13346-026-02230-6","DOIUrl":"https://doi.org/10.1007/s13346-026-02230-6","url":null,"abstract":"<p><p>Long-acting injectable formulations have emerged as promising systems for managing chronic psychiatric conditions by reducing dosing frequency and improving patient adherence. Oral antidepressants such as citalopram hydrobromide require daily administration, posing a significant risk of non-compliance in patients with Major Depressive Disorder (MDD). This study aimed to develop and characterize a poly (lactic-co-glycolic acid) (PLGA)-based in situ forming implant (ISFI) for the sustained parenteral delivery of citalopram hydrobromide over 10 days. Systematic formulation screening across polymers, solvents, and lipid excipients identified the optimized formulation (F4) composition, which was evaluated for viscosity, syringeability, in vitro drug release, ex vivo depot formation, release kinetics, cytotoxicity, and in vivo pharmacokinetic prediction. The optimized formulation exhibited Newtonian flow behavior (viscosity 0.35 Pa.s) with a maximum expulsion force of 16.49 N through a 20G needle, confirming adequate injectability. The in vitro release profile demonstrated a moderate initial burst of ~ 13% within 24 h, followed by near-linear sustained release reaching ~ 87% by Day 10. The Korsmeyer-Peppas model provided the best fit (R² = 0.99, n = 0.865), confirming Super case II and non-Fickian diffusion-erosion transport. A strong in vitro-ex vivo correlation (R² = 0.9259) validated the release model. Cytotoxicity assessment confirmed biocompatibility with an IC₅₀ of 34.92 ± 2.28 µg/mL, representing a 300-fold safety margin above therapeutic plasma concentrations. Convolution-based pharmacokinetic prediction demonstrated sustained systemic exposure over 10 days from a single intramuscular injection. This study demonstrates the feasibility of a PLGA-based long-acting injectable platform for sustained citalopram delivery, supporting its potential utility in the management of Major Depressive Disorder.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro, ex vivo and in vivo evaluation of polyelectrolyte nanogels for mucosal vaccines.","authors":"Angela Bonaccorso, Annunziata Corteggio, Luciana D'Apice, Antonio Cardamone, Barbara Tomasello, Anna Rita Coppoletta, Micaela Gliozzi, Teresa Musumeci, Daniela Melillo, Tommaso Heinzl, Cristina Carresi, Vincenzo Musolino, Vincenzo Mollace, Anam Farhan, Paola Italiani, Donato Cosco, Claudia Carbone, Rosario Pignatello","doi":"10.1007/s13346-026-02227-1","DOIUrl":"https://doi.org/10.1007/s13346-026-02227-1","url":null,"abstract":"<p><p>Nasal administration is investigated as an effective mucosal site suitable for non-invasive vaccine delivery and able to elicit both systemic and mucosal immunity. Delivery of proteins across the epithelial barrier is a key point to induce an immune response. In this framework, nanogels are properly designed to present the delivered antigen to the immune system, promoting their targeting to specific immune populations. Nanogels for nasal administration based on dextran sulfate and ϵ-poly-L-lysine have been prepared by polyelectrolyte complexation. To unlock the potential of mucosal vaccination, we evaluated nanogel for their ability to enhance antigen delivery across mucus barriers and promote immune activation. Using fluorescein-labelled ovalbumin as a model antigen, we investigated how nanogel governs antigen transport, cellular uptake, and presentation. Produced results showed that nanogel combines favourable physicochemical properties with mucoadhesive behaviour, enabling efficient interaction with the mucus layer. This translates into enhanced uptake and controlled intracellular trafficking in murine Bone Marrow-derived-Dendritic Cells, ultimately promoting effective antigen cross-presentation. Importantly, intranasal administration in vivo revealed prolonged antigen retention within the airway mucosa compared to the free antigen, indicating sustained local antigen availability. In addition, studies in human monocyte-derived macrophages provided preliminary information on the inflammatory response and intracellular fate of the nanogels in a human-relevant system. Together, these findings contribute to the preliminary preclinical characterization of the nanogel platform, while further studies are required to establish its immunogenicity and vaccine efficacy.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlled solvent removal dynamics during fabrication of microneedle patches for the sustained release of etonogestrel.","authors":"Jonathan Yuxuan Chen, Richard N Terry, Jie Tang, Tao Zheng, Steven P Schwendeman, Mark R Prausnitz","doi":"10.1007/s13346-026-02228-0","DOIUrl":"https://doi.org/10.1007/s13346-026-02228-0","url":null,"abstract":"<p><p>Biodegradable polymer-based microneedle (MN) patches enable self-administered, long-acting drug delivery. Controlled drug release from MNs requires controlled material distribution and minimal porosity in the MNs. MN detachment in the skin requires MNs without film formation beyond the MN base. To achieve these goals, we studied solvent removal dynamics during MN patch fabrication by a solvent-casting method to better control distribution of polymer and drug in the MN patch mold. More specifically, we designed casting solvents to control (i) solvent evaporation rate, (ii) solvent absorption rate into polydimethylsiloxane (PDMS) molds, and (iii) solubility of biodegradable polymer (poly (lactic acid)) and drug (etonogestrel, for long-acting contraception) in the solvent. We found that polymer film formation was prevented by using solvents with minimal mold absorption and moderate evaporation rates. We further demonstrated that solvent-nonsolvent mixtures titrated to the solubility limit of the polymer and beyond the solubility limit of the drug (forming a suspension of fine precipitate) also produced MNs without films. This occurred even when using solvents that absorbed into the molds. To better achieve sustained drug release, we showed that centrifuge-based casting and heat annealing reduced surface and bulk MN porosity. The resulting MNs achieved efficient detachment in porcine skin and sustained release of etonogestrel for two months in-vitro. This study establishes a framework to control solvent removal dynamics during MN patch fabrication to optimize biodegradable polymer MNs for long-acting delivery of etonogestrel and other drugs.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The first formulation tailored for intraperitoneal delivery as a pressurised aerosol (PIPAC): doxorubicin-cisplatin as a fixed, ready-to-use drug combination.","authors":"Yaroslaw Sautkin, Ranjita Shegokar, Janek Kibat, Mona Kibat, Juergen Weinreich, Hans Schoenfelder, Marc André Reymond","doi":"10.1007/s13346-026-02229-z","DOIUrl":"https://doi.org/10.1007/s13346-026-02229-z","url":null,"abstract":"<p><p>Pressurised Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery system for treating peritoneal metastasis. No PIPAC-specific formulation is available, stability data under PIPAC conditions are lacking, and the drugs are used off-label. 85% PIPAC are performed using Doxorubicin (DOX) and Cisplatin (CIS). Formulation development adhered to Investigational Medicinal Product Dossier (IMPD) requirements, covering composition, manufacturing process and controls, characterisation of actives and excipients, and in-use and long-term stability, as well as preclinical validation, including sprayability and dose equivalence in peritoneal tissue. The drug composition meets defined pharmaceutical specifications, yielding a stable, ready-to-use aqueous solution containing 0.131 mg/mL DOX and 0.656 mg/mL CIS in 0.9% sodium chloride, buffered to pH 4.4-4.5. Manufacturing followed a scalable process with controlled pH, osmolality, and purity, and packaging ensured light protection. Characterisation confirmed stability, appropriate viscosity, and physicochemical integrity. Sprayability testing with the CapnoPen® device demonstrated consistent aerosolisation and no drug-device incompatibility. A 200 mL volume provided optimal tissue uptake and lowest aerosol sedimentation, outperforming 100 mL and matching reference drugs. Tissue bioavailability of DOX and CIS was comparable to that of separate drug administration. Usability studies showed simplified handling, reduced equipment needs and minimised exposure risks. The diluted solution was stable for up to 30 h at room temperature, while long-term stability at 5 °C (undiluted) preserved DOX for 9 months and CIS for 60 months. We developed a sprayable DOX-CIS formulation specifically tailored for PIPAC therapy. Overall, the DOX-CIS composition met the predefined quality, performance, and stability criteria for use in PIPAC.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEG-associated efficacy loss in lipid nanoparticles persists across formulation modifications for mRNA delivery.","authors":"Mariah L Arral, Namit Chaudhary, Katherine C Fein, Alexandra N Newby, Saigopalakrishna S Yerneni, Jilian R Melamed, Samuel T LoPresti, Daria M Strelkova Petersen, Kathryn A Whitehead","doi":"10.1007/s13346-026-02225-3","DOIUrl":"https://doi.org/10.1007/s13346-026-02225-3","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) are clinically proven mRNA delivery vehicles, and repeated administration is often required to maintain therapeutic or prophylactic benefit. However, a single dose can provoke adaptive immune responses against polyethylene glycol (PEG), a polymeric excipient on the LNP surface. In this event, resultant anti-PEG antibodies neutralize subsequent LNP doses, causing efficacy loss and limiting therapeutic utility. Here, we investigated whether altering the LNP formulation between initial and subsequent doses could mitigate PEG-associated efficacy loss. Following the administration of an LNP known to elicit anti-PEG antibodies, we re-dosed with LNPs formulated with varied PEG-lipid chemistry, PEG concentration, mRNA cargo, and administration route. None of these adjustments prevented efficacy loss, which consistently correlated with elevated anti-PEG immunoglobulin M (IgM) and, in some cases, immunoglobulin G (IgG). Reduced PEG concentration diminished immunogenicity but also potency, and intraperitoneal dosing elicited the strongest responses upon repeat injection. Further, LNPs that elicit anti-PEG antibodies also impaired the subsequent delivery of an FDA-approved MC3 formulation, suggesting that anti-PEG immune responses can compromise any PEGylated LNP formulation. Together, these findings demonstrate that PEG-associated efficacy loss cannot be resolved through formulation optimization alone, when the ionizable lipid fails to engage the innate immune receptors TLR4 and CD1d. Instead, they suggest that the ionizable lipid's engagement of innate immune receptors is the primary determinant of repeat dosing success.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and characterization evaluation of sustained-release dissolving microneedles with skin soothing function.","authors":"Yuting Yang, Tingting Zhang, Yan Zhang, Liting Liu, Fanda Meng","doi":"10.1007/s13346-026-02080-2","DOIUrl":"10.1007/s13346-026-02080-2","url":null,"abstract":"<p><p>In recent years, microneedles (MNs) have drawn significant attention as a new strategy for drug delivery. Especially, dissolving microneedles (DMNs) are the most suitable system for their degradability and low biological hazard. However, MNs will inevitably cause skin irritation, which needs to be improved. The goal of this study is to develop soothing and sustained-release DMNs to reduce skin irritation during drug delivery. The MNs were successfully fabricated using biocompatible sodium hyaluronate, resilient hydroxyethyl cellulose, and γ-polyglutamic acid, which possess skin repair functions. An orthogonal experiment was designed and the performance of different DMNs was characterized to explore the optimal formation, including morphology and mechanical performance. We found that the optimal formulation was 13% HA-Na, 7% HEC and 5% γ-PGA at 30℃ for 3 h. The morphology of the DMNs had structural integrity with sharp tips and a uniform array. They could withstand a force of up to 20 N without fracture, demonstrating sufficient mechanical strength for skin penetration. Subsequently, further characterization of the optimal formulation of DMNs was performed, including skin penetration ability, compression resistance, and in vitro/in vivo dissolution behavior. The DMNs successfully penetrated porcine skin and simulated skin models under a force of 2 N. In vivo dissolution in mouse skin was completed within 1 h, supporting their soothing and sustained-release potential. The skin repair function was validated through a skin irritation experiment; the mice treated by DMNs with 5% γ-PGA had no erythema and edema during the whole process and the pinholes were observed to fully disappear in 5 min, indicating rapid skin repair function. Through these tests, our fabricated DMNs possessed soothing and sustained-release properties and skin repair function. To further realize the drug delivery application of the DMNs, some experiments should be conducted in the future, including drug loading and transdermal release performance.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3919-3934"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective topical delivery of minoxidil via chitosan coated nanocapsules to remodel microenvironment of dermal follicle for hair regeneration.","authors":"Jin Sil Lee, Tae Eon Park, Panmo Son, Hyeryeon Oh, Su Bin Lee, Sunghyun Kim, Jeung-Hoon Lee, Ki Su Kim, Won Il Choi","doi":"10.1007/s13346-026-02072-2","DOIUrl":"10.1007/s13346-026-02072-2","url":null,"abstract":"<p><p>Hair loss is a prevalent dermatological disorder that significantly affects quality of life. Among FDA approved treatments, topically applied minoxidil is commonly used. Nevertheless, its low water solubility necessitates use of irritating solvents which hinder its clinical administration. Since these solvents usually cause adverse reactions, nanotechnology-based carriers have emerged as promising strategies for topical delivery of minoxidil. Thus, we prepared topical delivery nanocarriers, i.e., chitosan-coated nanocapsules (ChiNCs), to increase percutaneous delivery through intrinsic characteristics of chitosan and to increase encapsulation of minoxidil into the nanocarriers. ChiNCs were prepared through simple nanoprecipitation and encapsulated in high amounts of minoxidil. The minoxidil-loaded ChiNCs (MXD@ChiNCs) were evaluated for their physicochemical characteristics, colloidal stability, release profile, skin penetration, cytotoxicity, proliferation, hair growth via animal, and histological analyses. MXD@ChiNCs were successfully loaded with 50 wt.% of MXD and maintained good stability. Additionally, release profile of MXD from MXD@ChiNCs exhibited sustained release behavior and improved skin penetration. Particularly, ChiNCs showed no cytotoxicity in skin-related cell lines and did not influence cell proliferation. MXD@ChiNCs demonstrated dose-dependent therapeutic efficacy and considerably boosted hair regrowth compared to other MXD formulations, as evidenced by macroscopic and histological results. These observations highlight potential of MXD@ChiNCs as topical delivery system for alopecia.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3817-3832"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancement in therapeutic application of quantum dots in amyotrophic lateral sclerosis: current opportunities and challenges.","authors":"Vivek Bakshi, Binay Pathak, Ankit Majie, Arya Ghosh, Abhinav Gupta, Neha Jain, Manisha Pandey, Anroop B Nair, Shery Jacob, Papiya Mitra Mazumder, Neelima Sharma, Nimmy Kumari, Bapi Gorain","doi":"10.1007/s13346-026-02082-0","DOIUrl":"10.1007/s13346-026-02082-0","url":null,"abstract":"<p><p>Despite advancements in healthcare settings in developed countries, the early detection and higher mortality rate associated with amyotrophic lateral sclerosis (ALS), a fatal motor neuronal disorder, remain challenging. Recently, quantum dots (QDs) have emerged as a promising nanocarrier in the prognosis and treatment of ALS owing to their unique multifunctional properties. QDs, through their photoluminescence properties upon excitation, can facilitate the identification and real-time monitoring of disease biomarkers. They also act as a nanocarrier for the targeted delivery of therapeutics, avoiding accumulation at the non-targeted sites and minimising toxicity. QDs can be fabricated to conjugate with protein biomarkers linked to ALS, such as specific proteins, nucleic acids, or genetic variants, for the diagnosis of the disease. Such fabrication could lead to enhanced identification and diagnostic patterns of ALS, thereby contributing to improved therapeutic intervention strategies. Furthermore, these tiny structures could be applied in combined biosensor formats to identify ALS-associated biomarkers in body fluids, which would be a highly sensitive diagnostic system. Subsequently, comprehensive multiomics techniques have demonstrated improved identification of newer protein targets associated with neurological complications. Overall, QDs can be explored as a potential tool to identify biomarkers relevant to ALS, diagnose the disease at its early stages, and track the effectiveness of the treatment. The integration of QD with omic-based strategies and network analysis can potentially catalyse a breakthrough in the management of ALS. Therefore, this review aims to explore the application of QDs in ALS diagnosis and management, advancements in research, clinical trials, and patents.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3589-3607"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of poly(vinyl alcohol)/poly(N-vinyl caprolactam)-based hydrogel-forming microneedle for transdermal delivery of captopril: fabrication, characterization and in vivo antihypertensive activity test.","authors":"Siti Fatriyah, Noverra Mardhatillah Nizardo, Fadlina Chany Saputri, Hyungil Jung, Ahhyun Lee, Callista Andinie Mulyadi, Yohan Baptista Adidharma Willie, Mandeep Marwah, Delly Ramadon","doi":"10.1007/s13346-026-02079-9","DOIUrl":"10.1007/s13346-026-02079-9","url":null,"abstract":"<p><p>Transdermal drug delivery systems, including microneedles (MNs), offer advantages over oral administration by bypassing gastrointestinal degradation and first-pass metabolism, while also reducing injection-associated pain. Hydrogel-forming microneedles (HFMNs) represent a promising advancement in this field as an alternative strategy. This study aimed to develop an HFMN using poly(vinyl alcohol)/poly(N-vinyl caprolactam) (PVA/PNVCL) with citric acid (CA) as crosslinking agent for transdermal delivery of captopril as a drug model. The HFMNs fabrication was optimised by varying crosslinking time, PNVCL concentration, and CA concentration. Evaluations were conducted on physical properties, mechanical strength, insertion ability, in vitro permeation, and drug content. In vivo skin irritation and antihypertensive efficacy tests were also assessed. A crosslinking time of 45 min, CA concentration of 1.0%, and 10% PNVCL significantly increased the insertion ability, swelling index, permeability and mechanical strength of the HFMNs. Among six formulations, F3 (PVA 15%; PNVCL 10%; CA 1%) demonstrated the most promising performance, achieving in vitro permeation of 66.68 ± 2.78%. In vivo studies showed that oral and transdermal delivery of captopril effectively lowered blood pressure in hypertension-induced rats, with transdermal delivery showing superior efficacy, which warrants further clinical investigation. In addition, in the in vivo skin irritation test, it was observed that HFMNs did not cause irritation. The optimised hydrogel-forming microneedles demonstrated enhanced mechanical strength, permeability, and drug delivery performance. Captopril transdermal delivery using PVA/PNVCL-based HFMNs showed superior antihypertensive efficacy compared to oral administration, with no skin irritation observed, supporting its potential for safe and effective clinical application.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3901-3918"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pirfenidone-exosomes as innovative strategies for scarless tissue repair in wound healing.","authors":"Jin Wang, Chen Sun, Emmanuel A Ho","doi":"10.1007/s13346-026-02108-7","DOIUrl":"10.1007/s13346-026-02108-7","url":null,"abstract":"<p><p>To facilitate scarless wound healing, developing an anti-scarring treatment that modulates dermal fibroblast activity is a promising strategy, with pirfenidone (PFD) showing potential due to its anti-fibrotic properties by targeting intracellular pathways that regulate collagen disposition. PFD, particularly when delivered via dermal fibroblast-derived exosomes, may further enhance therapeutic effectiveness and promote scarless healing. Two common isolation methods-PEG precipitation and affinity-based techniques-were compared to identify the most efficient approach for obtaining high-purity and relatively homogenous exosomes derived from human dermal fibroblasts. Characterization techniques, including transmission electron microscopy (TEM), atomic force microscopy (AFM), antibody arrays, and enzyme-linked immunosorbent assays (ELISA), confirmed the successful isolation of high-purity exosomes. The affinity-based method demonstrated superior performance, yielding well-dispersed and highly pure exosomes. We optimized the encapsulation and formulation of the antifibrotic compound PFD by exploiting exosomes as a drug delivery platform, employing an active loading method via sonication to enhance encapsulation efficiency (EE%) and loading efficiency (LE%), while carefully controlling the sonication process to preserve exosome integrity. The optimal formulation of PFD-exosomes achieved an EE% of 11.14% ± 1.27% and an LE of 10.01% ± 1.03%, with a particle recovery rate of exosomes at 64.21% ± 8.49% using sonication technique. Then, we investigated how to harness exosomes and PFD-exosomes as innovative strategies for achieving scarless tissue repair in wound healing. Our findings showed that exosomes enhanced fibroblast migration and proliferation, highlighting their potential as a stand-alone cell-free therapy for wound healing. Additionally, this study was ground-breaking in demonstrating that exosomes can improve the efficacy of PFD as a drug carrier, amplifying its anti-fibrotic effects in both in vitro and in vivo models. The in vivo results indicated that PFD-exosomes accelerated wound healing while organizing the extracellular matrix (ECM) by reducing excessive collagen deposition. Overall, PFD-exosomes present an innovative strategy for pre-scarring interventions, offering benefits of enhanced wound healing outcomes while minimizing scarring.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3935-3955"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}