Drug Delivery and Translational Research最新文献

{"title":"Antimicrobial efficiency of pH-responsive PAA/PAH-coated and flucloxacillin loaded titanium implants in the Galleria mellonella model.","authors":"Sarah Menke, Dennis Kollofrath, Nina Ehlert, Janin Reifenrath, Katharina Doll-Nikutta, Andreas Winkel, Sebastian Polarz, Andreas Kampmann, Nils-Claudius Gellrich, Philippe Korn","doi":"10.1007/s13346-026-02221-7","DOIUrl":"https://doi.org/10.1007/s13346-026-02221-7","url":null,"abstract":"<p><p>Implant-associated infections are a leading cause of implant failure in orthopedics and dentistry, often necessitating revision surgery. These infections arise primarily from biofilm formation on implant surfaces, which shields pathogenic microorganisms from host immunity and systemic antibiotics. To address this issue, we used a pH-responsive poly(acrylic acid)/poly(allylamine hydrochloride) (PAA/PAH) coating applied to nanostructured titanium rods with controlled nanotube pore sizes and loaded with flucloxacillin (FCX) to address Staphylococcus aureus infections. The release behavior of FCX from the PAA/PAH coating was first evaluated in vitro under different pH conditions. Drug release and antibacterial efficacy were assessed using UV-Vis spectroscopy to detect released FCX, optical density measurements at 600 nm for bacterial growth inhibition monitoring, as well as bacterial viability assays. In vitro experiments revealed that FCX release increased markedly under acidic conditions, whereas minimal release was observed at neutral pH. The antibacterial efficacy of the FCX-loaded coating was subsequently evaluated in vivo using the Galleria mellonella implantation model as a biologically relevant and ethically acceptable platform. Treatment efficacy was quantified by a five-day survival analysis. Controlled nano-structuring of the titanium surface alone did not affect larval survival. In addition, the tolerability of FCX and the dose-dependent antimicrobial activity of FCX against S. aureus were assessed under planktonic conditions, followed by implantation of FCX-loaded, S. aureus colonized titanium rods. Overall, the FCX-loaded PAA/PAH coating was associated with improved larval survival under both experimental conditions, highlighting its potential as a localized antimicrobial strategy for implantable medical devices.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105699","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":"Dual mucoadhesive nanoparticle-hydrogel platform for sustained intravaginal miconazole delivery with anti-biofilm activity against vulvovaginal candidiasis.","authors":"Muhammad Usman Khan, Naveed Ahmed, Arooj Komal, Hadayat Ullah, Syed Damin Abbas Hamdani, Asim Ur Rehman","doi":"10.1007/s13346-026-02224-4","DOIUrl":"https://doi.org/10.1007/s13346-026-02224-4","url":null,"abstract":"<p><p>Vulvovaginal candidiasis (VVC), primarily caused by Candida albicans, remains a global health concern, and conventional therapies struggle to maintain effective drug concentrations at the infection site. Miconazole (MIC)-loaded polymeric nanoparticles (MIC-PNPs) were prepared by nanoprecipitation, and Eudragit E 100 concentration, polyvinyl alcohol concentration, and organic-to-aqueous phase ratio were optimized using Design Expert® software. The optimized nanoparticles showed nanometric size, high zeta potential, and excellent entrapment efficiency. Fourier-transform infrared spectroscopy confirmed component compatibility, X-ray diffraction and differential scanning calorimetry indicated conversion of MIC to an amorphous state, and scanning electron microscopy revealed spherical morphology. MIC-PNPs were incorporated into a Carbopol-934 hydrogel (MIC-PNPG), which was characterized for physical properties, drug content, spreadability, mucoadhesive strength, and viscosity. MIC-PNPs and MIC-PNPG released 68% and 58% of MIC, respectively, over 24 h at pH 4.2, following Korsmeyer-Peppas kinetics. MIC-PNPG showed substantial ex vivo mucoadhesive strength. Antifungal assays confirmed superior activity of MIC-PNPs over free MIC, and antibiofilm studies showed concentration-dependent inhibition and degradation of C. albicans biofilms, with MIC-PNPG outperforming MIC-PNPs and free MIC. The hen's egg test-chorioallantoic membrane assay showed significantly lower irritation for nanoparticle-based formulations than the marketed product. Ex vivo studies demonstrated enhanced drug permeation and vaginal tissue retention of MIC-PNPs. In vivo, treatment significantly reduced infection pathogenicity, supported by histopathological findings. These results suggest MIC-PNPs as a promising candidate warranting further clinical investigation for VVC treatment.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073905","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":"Formulation development and in vitro evaluation of extemporaneous mucoadhesive in situ forming orals gels for localized therapy.","authors":"Radha Kulkarni, Rajesh V Lalla, Muhammad Faheem Hassan, Mu Ping Nieh, Saurabh Bhorkade, Diane J Burgess","doi":"10.1007/s13346-026-02223-5","DOIUrl":"https://doi.org/10.1007/s13346-026-02223-5","url":null,"abstract":"<p><p>Oral mucositis is a debilitating complication of head and neck cancer therapy, characterized by ulceration and moderate to severe pain, often leading to treatment de-escalation, malnutrition, and reduced quality of life. Bupivacaine-loaded thermosensitive mucoadhesive in situ gels have previously demonstrated prolonged oral residence and superior localized analgesia. The goal of this study is to develop a systematic and scalable formulation development approach to prepare hospital-compoundable mucoadhesive in situ forming oral gels using a pre-approved bupivacaine HCl injection. Sodium carboxymethyl cellulose (sodium CMC) was selected as the mucoadhesive polymer, while Pluronic^® F127 served as the thermosensitive component. A comprehensive evaluation of formulation variables, including polymer concentration, viscosity grade, and the degree of substitution revealed significant effects on the critical quality attributes. Increasing sodium CMC concentration initially enhanced mucoadhesion; however, excessive levels increased viscosity, reduced polymer hydration, and consequently decreased mucoadhesion and gelation temperature. Higher Pluronic^® F127 concentrations increased gel consolidation within hexagonal liquid crystalline structures, thereby slowing drug release. Converse to the conventional understanding, low-viscosity sodium CMC exhibited higher steady-state viscosity and more sustained drug release compared to the oral gels containing medium viscosity and high viscosity sodium CMC. The cumulative drug release at 8 h and the release kinetics were directly proportional to the degree of substitution of sodium CMC. This study represents one of the earliest systematic investigations into the complex interplay between formulation parameters and performance characteristics of mucoadhesive thermosensitive oral gels and establishes a novel structured approach for their rational formulation development. The knowledge and insight gained through this research will inform cost effective and accelerated formulation development of extemporaneous mucoadhesive in situ forming gels for different drug delivery applications.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073909","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":"Spray drying-assisted development of hydroxypropyl methylcellulose acetate succinate microparticles for andrographolide delivery: an in-vivo study in experimental ulcerative colitis.","authors":"Pawan Devangan, Hoshiyar Singh, Soyal Sayyed, Santosh Kumar Guru, Jitender Madan","doi":"10.1007/s13346-026-02218-2","DOIUrl":"https://doi.org/10.1007/s13346-026-02218-2","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease distinguished by colonic inflammation and mucosal injury; therefore, targeted suppression of underlying inflammatory pathways represents a rational strategy for developing an effective drug delivery system. In the current investigation, Andrographolide (ADG) loaded pH-responsive hydroxypropyl methylcellulose acetate succinate-based microparticles (ADG-HPMC-AS MPs) were engineered by spray-drying technique and optimized using Box-Behnken Design to achieve desirable physicochemical and biopharmaceutical attributes. Optimized ADG-HPMC-AS MPs exhibited particle size 9.25 ± 0.89 µm, zeta potential (ζ) -0.80 ± 0.70 mV, drug loading 8.97 ± 0.49%, entrapment efficiency 53.81 ± 2.96%, and spherical shape. Next, a plethora of solid-state analyses validated effective ADG encapsulation, improved thermal stability, and amorphous nature, stabilized by intermolecular interactions. ADG-HPMC-AS MPs displayed minimal drug release under acidic medium, while drug release was observed up to 24 h in colonic milieu. Later, therapeutic efficacy of ADG-HPMC-AS MPs was tested against TNBS-induced UC and demonstrated superior efficacy in DAI and CMDI scores. ADG-HPMC-AS MPs caused significant (P ≤ 0.0001) down-regulation of NF-κB (0.75-fold), STAT3 (2.12-fold), and p-STAT3 (1.15-fold) expression relative to positive control. ADG-HPMC-AS MPs produced marked suppression of mRNA expression (IL-1β, IL-6, TNF-α, COX-2, iNOS, and MMP-9) in TNBS-induced UC. ADG-HPMC-AS MPs-treated group markedly ameliorated epithelial damage, inflammatory infiltration, and collagen deposition, demonstrating lowest histopathological scores compared to positive control. These findings validate ADG-HPMC-AS MPs as a drug delivery system that ameliorates UC by attenuating oxidative stress and NF-kB/STAT3-driven signalling. In conclusion, ADG-HPMC-AS MPs may serve as a promising drug-delivery system for improving the therapeutic potential of ADG in the effective management of UC.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059278","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":"Localized immunotherapy via dissolving microneedles for the prevention of breast cancer recurrence.","authors":"Neha Rathi, Shubham Kanaujiya, Kartik Mittal, Gond Kanchankumari Subhashchandra, Lamu Bhotiya, Prashant Pandey, Anit Kumar, P S Rajinikanth","doi":"10.1007/s13346-026-02217-3","DOIUrl":"https://doi.org/10.1007/s13346-026-02217-3","url":null,"abstract":"<p><p>Breast cancer recurrence post-surgery poses a significant clinical challenge, driven by a paradoxically immunosuppressive wound-healing environment that fosters metastatic relapse. While systemic therapies face dose-limiting toxicities, existing localized platforms like hydrogels and implants lack patient self-administration capabilities. This review evaluates dissolving microneedle (DMN) patches as an innovative, self-administrable, fully bioresorbable transdermal platform for post-surgical immunotherapy. Compared to other microneedle types, DMNs uniquely meet all functional requirements: localized delivery, systemic toxicity mitigation, tunable release, self-administration, and complete resorption. We discussed preclinical advances in biomaterials, cargo design (including STING agonists, TLR7/8 ligands, cytokines, and checkpoint inhibitors), and stimuli-responsive release mechanisms. A novel \"kill-reveal-remember\" framework is proposed integrating immunogenic cell death, localized checkpoint blockade, and immune memory formation within a single patch. Triple-negative breast cancer (TNBC) is identified as the primary clinical target due to its early recurrence and immunogenicity. However, significant translational hurdles remain. Current preclinical evidence is limited by exclusive use of the murine 4T1 model, short rechallenge intervals, and lack of tissue-resident memory T cells. Furthermore, GMP-compliant manufacturing, sterilization protocols, and stability data are lacking. Successful clinical translation will require advanced humanized models, standardized DMN specifications, and biomarker-driven trials using circulating tumor DNA to fully realize this localized immunotherapeutic approach. Overall, DMN-based localized immunotherapy holds considerable promise for preventing post-surgical breast cancer recurrence by enabling targeted immune modulation with reduced systemic toxicity.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036984","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":"Smart drug delivery systems for immunotherapeutic agents: focus on biological/biogenic platform-based intelligent delivery in cancer immunotherapy.","authors":"Parisa Abbasi, Arvin AfsharManesh, Samaneh Rezaei, Mojtaba Mozdi, Parisa Shakeri, Niloofar Khandan-Nasab, Davood Zaeifi, Khadijeh Jamialahmadi, Reza Kazemi Oskuee","doi":"10.1007/s13346-026-02222-6","DOIUrl":"https://doi.org/10.1007/s13346-026-02222-6","url":null,"abstract":"<p><p>Cancer immunotherapy marks a major advance in oncology, yet its effectiveness is constrained by challenges such as inefficient tumor targeting, immune-related toxicities, low response rates, and an immunosuppressive tumor microenvironment (TME). To overcome these obstacles, smart drug delivery systems (SDDSs) have been developed to deliver immunotherapeutic agents in a targeted, controlled manner in response to specific stimuli. This review summarizes recent advances in SDDSs for cancer immunotherapy, focusing on biological and biogenic platforms. These systems respond to endogenous and exogenous stimuli to improve treatment precision and enhance antitumor immune responses. The main types of SDDS, including synthetic, biological, and hybrid, are reviewed in the context of applications such as immune checkpoint inhibition, cancer vaccines, cytokine therapy, and adoptive cell therapy. The review also considers engineered exosomes, including isolation and engineering strategies, microRNA (miRNA) loading strategies, and surface modifications to improve targeting and impact on the TME. Existing evidence suggests that biological and hybrid platforms offer advantages in biocompatibility, biological recognition, and functional versatility; however, challenges remain in cargo-loading efficiency, biological heterogeneity, scalability, safety, and reproducibility. Emerging approaches, including clustered regularly interspaced short palindromic repeats (CRISPR)-based engineering, hybrid nanocarriers, and artificial intelligence, can accelerate the development of advanced immunotherapy delivery systems. Overall, biointegrated SDDSs show potential for greater precision, efficacy, and safety in cancer immunotherapy, although significant barriers to their clinical application remain.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024375","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":"Chitosan-TPP modification of SNEDDS enhances mucin interaction, apparent epithelial transport, and oral exposure of ezetimibe.","authors":"Ju Young Lee, Ji Ho Song, Jung Hyun Cho","doi":"10.1007/s13346-026-02219-1","DOIUrl":"https://doi.org/10.1007/s13346-026-02219-1","url":null,"abstract":"<p><p>Poor aqueous solubility limits the oral absorption of ezetimibe, and conventional self-nanoemulsifying drug delivery systems (SNEDDS) primarily address the solubilization barrier. In this study, ezetimibe-loaded SNEDDS were associated with a chitosan-tripolyphosphate (TPP) ionic network to generate chitosan-TPP-modified SNEDDS colloids (CS-SNEDDS) with additional mucin-interactive characteristics. The resulting CS-SNEDDS had a mean particle size of approximately 142 nm and a positive zeta potential, while retaining the apparent solubilization and rapid dispersion properties of the SNEDDS component. Compared with conventional SNEDDS, CS-SNEDDS showed markedly greater mucin association and increased apparent apical-to-basolateral transport across Caco-2 monolayers. Following oral administration to rats, CS-SNEDDS produced an AUC₀-₂₄h of 4715.62 ± 854.07 ng·h/mL, compared with 3647.39 ± 753.54 ng·h/mL for SNEDDS and 2176.84 ± 426.58 ng·h/mL for crystalline ezetimibe. The AUC₀-₂₄h of CS-SNEDDS was significantly higher than that of SNEDDS, whereas no significant difference in C_max was detected between the two nanoformulations. These findings indicate that chitosan-TPP modification of ezetimibe-loaded SNEDDS introduced mucin-interactive cationic properties and was associated with an additional improvement in apparent epithelial transport and systemic exposure beyond that achieved by SNEDDS alone. This lipid-polymer interfacial modification strategy may provide a useful formulation approach for improving the oral delivery of poorly water-soluble drugs.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982342","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":"Coptis chinensis -derived nanovesicle-loaded biodegradable hydrogel for preventing post-laminectomy epidural fibrosis.","authors":"Sichu Wang, Li Tong, Wei Chen, Can Peng, Yu Yao, Baogang Zhang, Jiawei Ji","doi":"10.1007/s13346-026-02216-4","DOIUrl":"https://doi.org/10.1007/s13346-026-02216-4","url":null,"abstract":"<p><p>Post-laminectomy epidural fibrosis (PLEF) is a major contributor to failed back surgery syndrome, yet current preventive strategies remain unsatisfactory. Here, we engineered an injectable, biodegradable methacrylated hyaluronic acid-phenylboronic acid (HAMA-PBA) hydrogel incorporating Coptis chinensis-derived nanovesicles (CCNVs) for localized PLEF prevention. Characterization confirmed the successful isolation of nanoscale CCNVs and their uniform three-dimensional distribution within the hydrogel matrix. In vitro, the CCNVs-loaded hydrogel significantly suppressed L929 fibroblast proliferation and migration, primarily by inhibiting the TGF-[Formula: see text]/Smad2 signaling pathway. In a rat laminectomy model, local application of the HAMA-PBA@CCNVs hydrogel markedly reduced epidural scar adhesion and fibrous tissue formation. Furthermore, systemic safety and excellent biocompatibility were confirmed across major organs. Overall, this CCNVs-loaded hydrogel provides a safe, targeted, and effective nanobiotechnology-based strategy to prevent post-surgical epidural fibrosis and improve spinal surgery outcomes.Clinical trial number: not applicable.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967183","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":"Aligning biopharma and academic partnerships to advance drug delivery technologies: insights from a multidisciplinary panel.","authors":"Jill M Steinbach-Rankins, Christine J Allen, Mark R Prausnitz, Ronald J Pettis, Manuel Sanchez-Félix","doi":"10.1007/s13346-026-02212-8","DOIUrl":"https://doi.org/10.1007/s13346-026-02212-8","url":null,"abstract":"<p><p>The field of drug delivery is undergoing rapid transformation, driven by advances in biotherapeutics, new modalities, and innovative delivery technologies. However, translating these scientific breakthroughs into patient-centric therapies requires overcoming significant scientific, translational, and organizational barriers. This perspective piece provides insights from a multidisciplinary panel of leaders in biopharma, academia, and start-up innovation, focusing on the most promising opportunities and persistent challenges in the field. The discussion highlights the renewed and increased focus on subcutaneous and microneedle-based delivery systems, the evolving role of nanoparticle delivery, and the importance of aligning research with clinical and market needs through early cross-sector collaboration. The panel underscored the need for early stakeholder engagement, transparent communication, and iterative feedback to integrate business case considerations from the outset and foster successful partnerships. Various collaborative models that include pre-competitive consortia, open innovation incubators, public-private partnerships, and entrepreneurial training, are discussed for their effectiveness in bridging the gap between academic discovery and clinical translation. Ultimately, the advancement of drug delivery depends on multidisciplinary collaboration, robust translational frameworks, and sustained investment in innovative, patient-focused solutions that address real-world needs and improve patient outcomes.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918559","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":"Cooling-triggered sciatic nerve block using thermoresponsive hydrogel implants.","authors":"Romario Lobban, Andrew G Ray, Mailee Srilouangkhol, Fang Yu, Phoebe Kelso, Isabel Madrid, Katelyn Derr, Katherine Young, Katherine N Gibson-Corley, Craig L Duvall, Leon M Bellan","doi":"10.1007/s13346-026-02215-5","DOIUrl":"10.1007/s13346-026-02215-5","url":null,"abstract":"<p><p>Opioids remain the standard of post-operative pain management despite their known addiction risks. Local anesthetics, like bupivacaine, offer a safer, non-systemic alternative; however, existing delivery methods are either inconvenient, painful, or require complex equipment. Herein, we describe an implantable drug delivery device that leverages the cooling-triggered, reversible gel-to-sol transition of poly-N-isopropylacrylamide [PNIPAM] (achieved by simple icepack cooling, a pain-relief strategy already familiar to patients) for on-demand release of bupivacaine hydrochloride. Conveniently, this system allows on/off drug release over multiple cycles, as the drug release rate is significantly reduced when the cooling stimulus is removed but can be restored upon subsequent reapplication of cooling. We detail device fabrication and cooling-triggered release testing of a model dye and the drug of interest both in vitro and in vivo, with thermal latency testing on Sprague-Dawley rats used to demonstrate cooling-triggered sensory nerve block. Our results establish cooling as an intuitive trigger for delivery of local anesthetics, offering a promising route to patient-controlled, repeatable pain relief that could reduce opioid dependency in post-operative care.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918585","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}