Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
A gel-forming antioxidant eye drop for photoreceptor protection in retinitis pigmentosa.
Appell MB, Kanan Y, Malmberg K … +4 more , Appidi T, Khan M, Campochiaro PA, Ensign LM
Drug Deliv Transl Res · 2026 Apr · PMID 41661511 · Full text
Retinitis pigmentosa (RP) is a chronic genetic condition that leads to progressive loss of photoreceptor cells and vision. While gene therapy is available for a small subset of patients with specific mutations, developin...
Retinitis pigmentosa (RP) is a chronic genetic condition that leads to progressive loss of photoreceptor cells and vision. While gene therapy is available for a small subset of patients with specific mutations, developing a therapeutic that broadly targets the cellular stresses that lead to cell death could address a major unmet need. One such option would be utilizing antioxidant therapies to neutralize reaction oxygen species (ROS) in the retina that underlie RP progression. Here, we describe an approach for delivering the antioxidants N-acetyl cysteine (NAC) or N-acetyl cysteine ethyl ester (NACET) with a gel-forming eye drop previously demonstrated to provide therapeutic drug delivery in the posterior segment in animals. We demonstrated therapeutic protection of photoreceptor structure and function in a chemically-induced rat model of RP (48% increase in photopic b-wave amplitude), as well as some limited protection in an aggressive genetic mouse model (rd10) of retinal degeneration (~ 31% increase in photopic b-wave amplitude) with once daily application. However, antioxidants have inherent stability issues when stored in solution, so we investigated the use of additional excipients to improve stability and retain potency. While a promising approach, future work to address product stability and efficacy in larger eyes is needed for further development.
Microneedles self-implanting Astragalus polysaccharides-hybridized composite hydrogel combined with minoxidil to enhance in situ anti-androgenetic alopecia.
Li J, Long M, Xu F … +5 more , Abudureyimu Z, Li J, Guo T, Feng N, Zhang Y
Drug Deliv Transl Res · 2026 Feb · PMID 41654686 · Publisher ↗
In the current study, polysaccharides (APS) extracted from the dried roots of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao were demonstrated to promote hair regeneration. However, with an average m...
In the current study, polysaccharides (APS) extracted from the dried roots of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao were demonstrated to promote hair regeneration. However, with an average molecular weight of 20,000, they exhibit poor transdermal absorption. To enhance local efficacy, we synthesized chemically crosslinked hyaluronic acid (cHA) and prepared γ-cyclodextrin-modified potassium metal-organic frameworks (MOFs) loaded with minoxidil (MDX) (MDX@MOF).The aforementioned materials were mixed with APS to form soluble microneedles (MDX@MOF-APS/cHA-MNs). Their oblique spike structure facilitates local fixation after skin penetration. MOF-based drug loading increased MDX water solubility by ninefold, while cHA provided significant sustained-release effects.Furthermore, APS enhances the mechanical properties of hydrogel microneedles and optimizes drug delivery. Notably, APS promotes human hair follicular papilla cell proliferation in a dose-dependent manner and exhibits synergistic effects with MDX. Concurrently, MDX@MOF-APS/cHA-MNs significantly prolong drug retention time in the skin, effectively improving hair coverage and growth rate in androgenetic alopecia mice. In summary, APS emerges as a clinical candidate for treating androgenetic alopecia, while novel microneedles with unique composition and structure enrich topical delivery strategies.
Engineered levothyroxine dry powder for inhalation to treat idiopathic pulmonary fibrosis.
Bazzoli G, Bianchera A, Trevisi G … +3 more , Fattal E, Vergnaud J, Bettini R
Drug Deliv Transl Res · 2026 Feb · PMID 41654685 · Publisher ↗
Interest in drug repurposing has increased significantly in recent decades owing to its potential to accelerate the development of new medicinal products, provide new therapeutic options for patients, and generate busine...
Interest in drug repurposing has increased significantly in recent decades owing to its potential to accelerate the development of new medicinal products, provide new therapeutic options for patients, and generate business opportunities for pharmaceutical companies. Idiopathic pulmonary fibrosis (IPF) is defined as a chronic disease that causes an irreversible loss of lung function and premature death. Recent studies have highlighted the key role of mitochondria in lung homeostasis and the ability of thyroid hormones to promote mitochondrial activity, suggesting their potential involvment in IPF pathogenesis. In this work, we translate the findings derived from the above-mentioned researches into a dry powder drug delivery system intended to target epithelial lung cells with levothyroxine. To this end we developed nano-embedded respirable microparticles by spray drying a nanosuspension composed of levothyroxine and a hydrophilic polymer. The powder was characterized in terms of physico-chemical, toxicological and aerodynamic performance, as well as for its ability to be internalized by A549 cells and modulate their metabolic activity. The nano-embedded microparticulate drug delivery system proved to be potentially able not only to reach the deep lung but also to promote levothyroxine internalisation and mitochondria activation.
Technical pen-based printhead for high-precision microdosing of personalized therapies.
Carou-Senra P, Rial C, Richter A … +3 more , Basit AW, Alvarez-Lorenzo C, Goyanes A
Drug Deliv Transl Res · 2026 Feb · PMID 41652175 · Publisher ↗
Additive manufacturing offers unprecedented opportunities for personalized medicine, but most pharmaceutical printing platforms are optimized for milligram-range doses, limiting their suitability for microdosing. This wo...
Additive manufacturing offers unprecedented opportunities for personalized medicine, but most pharmaceutical printing platforms are optimized for milligram-range doses, limiting their suitability for microdosing. This work introduces a novel liquid deposition approach using a modified technical pen integrated into a pharmaceutical printer. The gravity-driven mechanism enabled precise microscale dispensing without external thermal, pneumatic, or electrical inputs, which have been associated with molecular stress in other printing technologies. Desmopressin, a potent synthetic hormone indicated for diabetes insipidus and requiring ultra-low doses, was selected as a model compound. Oral films (2 × 4 cm) containing therapeutically relevant doses (33-134 µg) were produced by depositing up to four layers of pharmaceutical ink. A custom-developed software interface allowed precise control of key process parameters, supporting reproducibility and automated workflows. The system achieved ~ 100% dose accuracy, with a strong correlation between drug content and layer number. Films exhibited rapid disintegration and immediate release. Stability testing showed no drug degradation over one month. Unlike more complex printing platforms, the technical printhead architecture offered straightforward manipulation and rapid setup. Given the constant ink flow rate and low, consistent, deposition volumes, only 1 mL of formulation is sufficient to produce up to 238 single-layer 2 × 4 cm films. These findings position the technical pen-based printhead as a promising, precise, and cost-effective addition to the additive manufacturing landscape, with strong potential for low-dose personalized pharmaceutical applications, including biologics. Moreover, its performance underscores the potential for further optimization and broader application.
Magnetically controlled delivery capsule endoscopy for precise drug delivery to intestinal lesions.
He C, Jiang X, Zhang T … +4 more , Chen Y, Qiu X, Li Z, Liao Z
Drug Deliv Transl Res · 2026 Feb · PMID 41649738 · Publisher ↗
Current drug delivery devices can't deliver drugs toward targeted intestinal lesions non-invasively. A novel magnetically controlled delivery capsule endoscopy (MDCE) system was developed to accurately deliver topical th...
Current drug delivery devices can't deliver drugs toward targeted intestinal lesions non-invasively. A novel magnetically controlled delivery capsule endoscopy (MDCE) system was developed to accurately deliver topical therapy toward intestinal lesions under real-time optical visualization. We aimed to evaluate the feasibility and efficacy of this MDCE system in precisely targeted delivery of topical therapy. The delivery feasibility of the MDCE were first evaluated using an ex vivo swine intestinal model. In this model, simulated lesions (n = 27) were created and marked with a pre-selected dye (0.1% methylene blue). The MDCE delivery processes for small intestine lesions were conducted in four Bama miniature pigs. The feasibility of MDCE was defined as successful drug delivery to specific simulated small bowel lesion under optical surveillance. Efficacy was evaluated using parameters including image quality, maneuverability of the MDCE, and the time required for aiming and drug delivery taken by MDCE. The MDCE system demonstrated robust feasibility in an ex vivo intestinal model, achieving over 80% targeting success rate across 27 lesions at various orientations. This precision was successfully translated in vivo, with 91.7% (22/24) of target lesions precisely stained. Except for two raised lesions, 22 of them were precisely stained. The image quality and the maneuverability of the MDCE system were both graded as the best. Further analysis of procedural efficiency revealed that while the time for aiming lesions (16 s to 191 s) was longer in the small intestine than in the colon, especially when aiming at flat lesions (p = 0.0304), the rapid dye delivery time (4 s to 11 s) remained consistent across all locations and lesion types (p > 0.05). This study confirmed the feasibility and efficacy of the MDCE system for delivering targeted drug to specific intestinal lesions with real-time, vision-based monitoring in swine models.
Design parameter effects on controlled drug delivery through implantable hydrogels.
Jowell B, Zhan W
Drug Deliv Transl Res · 2026 Feb · PMID 41644929 · Publisher ↗
Glioblastoma recurrence after surgery is a major contributor to its high mortality, primarily occurring near the original tumour margin. Various hydrogels have been developed to fill the post-surgical cavity and deliver...
Glioblastoma recurrence after surgery is a major contributor to its high mortality, primarily occurring near the original tumour margin. Various hydrogels have been developed to fill the post-surgical cavity and deliver drugs to the surrounding brain tissue to eliminate residual cells. However, the impact of tissue, hydrogel, and drug properties on delivery outcomes remains unclear. Here, a parametric study is conducted to investigate these effects using mathematical modelling. The results show that post-surgical oedema strongly influences delivery: longer duration or delayed onset of oedema can homogenise drug distribution, with delayed onset yielding a larger and more sustained therapeutic drug volume. Hydrogels with higher permeability or lower drug affinity enhance early concentration and distribution but decline faster over time. Drugs with lower intracellular partitioning improve early efficacy, whereas those with stronger binding to cellular or extracellular components sustain delivery longer. Lower transvascular permeability and slower elimination further enhance outcomes, while extracellular diffusivity must be optimised to maximise drug concentration and distribution. These findings provide guidance for optimising hydrogel-based drug delivery systems to prevent glioblastoma recurrence.
Translation of pharmaceutical 3D printing to clinical point-of-care and industrial manufacturing.
Gioumouxouzis CI, Eleftheriadis GK, Kyriakidis AS … +1 more , Karavasili C
Drug Deliv Transl Res · 2026 Feb · PMID 41644928 · Publisher ↗
Three-dimensional printing of medicines is moving from feasibility to practice across hospital point-of-care manufacture, community-pharmacy compounding and industrial production. Recent signals include a point-of-care p...
Three-dimensional printing of medicines is moving from feasibility to practice across hospital point-of-care manufacture, community-pharmacy compounding and industrial production. Recent signals include a point-of-care printed oral solid dosage form that met bioequivalence in healthy adults, automated capsule preparation with embedded checks in pharmacies and the first approved industrial product. These advances suggest that 3D printing can deliver clinically acceptable quality when responsibilities, verification and documentation are in place. This review integrates evidence across all three settings and offers a critical appraisal of what is required for safe adoption. We examine how regulatory responsibilities should be allocated across distributed sites, how non-destructive testing and chemometric models can be validated for small batches and which digital systems are essential for traceability and oversight. We analyse where economics break even compared with conventional compounding and identify use cases where 3D printing is comparatively advantaged, including low-dose titration, paediatric formats and rapid design iteration. We also outline risks that must be managed, including training and competency, cleaning validation, cross-contamination control and pharmacovigilance across networks. Finally, we propose a near-term agenda that includes standardised conduct of point-of-care trials, multi-site cost and quality benchmarking, explicit guidance on recalls and labelling and deeper industrial-clinical partnerships to turn pilots into routine practice.
Beyond the dose: a clearance-enabled in vitro platform for evaluating local therapies.
Marway MK, Marway SK, Celejewski MB … +3 more , D'Angelo AD, Zhang B, Wylie RG
Drug Deliv Transl Res · 2026 Feb · PMID 41634507 · Publisher ↗
Inclusion of physiologically relevant clearance mechanisms into organ-on-a-chip models is essential to reproduce tissue exposure and predict therapeutic efficacy, especially for local therapies and drug delivery applicat...
Inclusion of physiologically relevant clearance mechanisms into organ-on-a-chip models is essential to reproduce tissue exposure and predict therapeutic efficacy, especially for local therapies and drug delivery applications that are already common in the clinic for ocular and cancer treatments. There remains a need for clearance-enabled organ-on-a-chips amenable to high throughput screening, especially with the emerging trend to expedite formulation and drug delivery vehicle (DDV) design with machine learning. To address this gap, we developed a microfluidic platform that incorporates continuous, pressure-driven clearance through interconnected microchannels and three-dimensional (3D) systems, enabling translational evaluation of local therapies and DDVs, such as injectable hydrogels, that aim to reduce systemic toxicity and enhance efficacy by prolonging drug residence at disease sites. In this study, fluorescent 4 and 65 kDa dextrans were used to confirm that pressure gradients across the platform promote efficient clearance versus passive diffusion. The pressure gradients were then applied to breast cancer spheroids co-cultured with macrophages in a fibrin hydrogel to evaluate the therapeutic efficacy of an interferon gamma (IFN-γ)-releasing agarose hydrogel in combination with anti-human epidermal growth factor receptor 2 (anti-HER2). Fluorescent imaging of spheroid area revealed increased cancer cell viability, lower drug efficacy, when continuous clearance was present, highlighting the impact of drug clearance. This study establishes the clearance-enabled microfluidic platform as a translationally relevant in vitro model for evaluating local therapies under continuous clearance, thereby bridging the gap between traditional static platforms and in vivo models for evaluating local pharmacokinetics and pharmacodynamics.
From bench to bulk: exploring in-line homogenization for scale-up and continuous production of vesicular systems.
Phatak KM, Yawalkar AN, Vavia PR
Drug Deliv Transl Res · 2026 Jan · PMID 41615623 · Publisher ↗
Nanovesicular systems hold a significant promise for drug delivery, yet their clinical translation is hindered by challenges in scalability and reproducibility. This study introduces in-line homogenization as a continuou...
Nanovesicular systems hold a significant promise for drug delivery, yet their clinical translation is hindered by challenges in scalability and reproducibility. This study introduces in-line homogenization as a continuous, organic solvent-free approach for scalable fabrication of bilayered unilamellar vesicles, NioTherms (Niosome-like) and ThermoSomes (Liposome-like), loaded with model hydrophobic (Posaconazole, PCZ) and hydrophilic (Dexamethasone Sodium Phosphate, DEX) drugs. Using a heat-mixing method as the baseline, formulations were scaled from 10 mL (1x) to 1 L (100x) via a rotor-stator-based in-line homogenizer. Process parameters including pump speed, homogenizer speed, cycle number, phase ratio and output rate were optimized. The resulting vesicles exhibited uniform particle size and entrapment efficiencies comparable to the lab-scale batches. The formation of vesicles, morphology, internal structure, and integrity of the formed particles was confirmed by TEM and SANS analysis. The system enabled rapid batch processing (< 5 min for 1 L) with substantial product yields up to 80%. The process demonstrated excellent reproducibility and eliminated the need for post-processing. This study establishes in-line homogenization as a robust, scalable platform for faster production of nanovesicular drug delivery systems, effectively bridging the gap between bench-scale development and continuous manufacturing.
A liposomal formulation of cyclosporine a shows promising results in treating symptoms of moderate to severe dry eye disease in dogs.
Caballo-González MÁ, Gómez-Ballesteros M, Brugnera M … +8 more , Benítez-Del-Castillo JM, González-Alonso-Alegre EM, Rodríguez-Álvaro A, de-Las-Heras B, Gil-Alegre E, Vicario-de-la-Torre M, Herrero-Vanrell R, Molina-Martínez IT
Drug Deliv Transl Res · 2026 Apr · PMID 41615622 · Full text
The prevalence of dry eye disease (DED) is rising globally, increasingly affecting young adults. Although artificial tears are commonly used, unfortunately they do not address the inflammatory component of the disease. F...
The prevalence of dry eye disease (DED) is rising globally, increasingly affecting young adults. Although artificial tears are commonly used, unfortunately they do not address the inflammatory component of the disease. For this reason, in patients whose symptoms persist despite the use of artificial tears, anti-inflammatory agents such as the immunosuppressant cyclosporine A (CyA) are clinically indicated to reduce the underlying inflammation in DED. In this study, a CyA-loaded liposomal formulations composed of analogous components to the lipid and aqueous layers of the natural tears (CyA-lipo) and dispersed in an aqueous solution of sodium hyaluronate (CyA-lipo-NaHa) has been developed. Formulations were analysed for physicochemical properties, and in vitro tolerance using human corneal and conjunctival cell lines over a short-term stability study at 25 °C and 2–8 °C. In vivo tolerance was assessed in rabbits, and therapeutic efficacy was evaluated in dogs diagnosed with DED. Average vesicles’ size resulted in 204.2 ± 4.3 nm and 198.7 ± 6.0 nm for CyA-lipo and CyA-lipo-NaHa respectively. Both formulations rendered osmolarity values close to 200 mOsm and surface tension values below 31 mN/m. The addition of sodium hyaluronate produced an increase of viscosity with values of 6.030 ± 0.316 mPa·s for CyA-lipo-NaHa and 0.950 ± 0.073mPa·s for CyA-lipo. Cell viability was above 80% in corneal and conjunctival cells, and no signs of ocular surface damage in rabbit were observed. In dogs, ocular surface parameters, Schirmer’s test values in particular, improved significantly after two months of treatment (< 13 mm/min before and higher than15 mm/min in all animals after treatment). This liposomal formulation demonstrates optimal physicochemical properties, biocompatibility, and therapeutic efficacy, supporting its potential as an optimised treatment for DED.
The RNA delivery dilemma-lipid versus polymer nanoparticle platforms.
Martins C, Mitchell MJ, Peer D … +4 more , Perrie Y, Siegwart DJ, Alonso MJ, Aparicio-Blanco J
Drug Deliv Transl Res · 2026 Jun · PMID 41615621 · Publisher ↗
Since the first market authorization of RNA therapies, just eight years ago, the field has witnessed an extraordinary expansion, ranging from hepatic delivery for rare genetic diseases to global-scale vaccination during...
Since the first market authorization of RNA therapies, just eight years ago, the field has witnessed an extraordinary expansion, ranging from hepatic delivery for rare genetic diseases to global-scale vaccination during the COVID-19 pandemic, and now to cutting-edge cancer vaccines and gene editing strategies entering late-stage clinical trials. In parallel, the RNA therapeutics landscape has evolved rapidly, progressing from small interfering RNAs to next-generation and combinatorial RNA modalities. None of these breakthroughs would have been possible without the development of sophisticated RNA delivery technologies capable of navigating complex biological environments, enabling precise cellular targeting, and facilitating efficient intracellular trafficking. In this Editorial Note, we take a step back to reflect on key lessons learned throughout the RNA delivery journey. Featuring insights from leading and experienced voices in the field, this manuscript highlights critical milestones, persistent challenges, and the roles of lipid nanoparticles (LNPs) and polymer nanoparticles (PNPs) as RNA delivery platforms. These experts reflect on the features that have positioned LNPs as the current RNA delivery gold standard, while also exploring the untapped potential and distinctive advantages of polymer-based nanosystems. Collectively, these perspectives underscore a striking truth: we are only beginning to unlock the full therapeutic potential of RNA, and nanomedicine will certainly continue to shape the future clinical translation of RNA-based therapies.
Dissolving microneedles incorporating kopexil multicomponent crystals for improved transdermal delivery.
Deng Y, Wong SN, Chan WCN … +2 more , Zhang X, Chow SF
Drug Deliv Transl Res · 2026 Jan · PMID 41606208 · Publisher ↗
Notwithstanding the rapid advancements in microneedle research, the applications of multicomponent crystals (MCCs) within microneedle drug delivery landscape remain largely underexplored. This study aimed at integrating...
Notwithstanding the rapid advancements in microneedle research, the applications of multicomponent crystals (MCCs) within microneedle drug delivery landscape remain largely underexplored. This study aimed at integrating crystal engineering with powder-carrying microneedle technology to overcome the current therapeutic obstacles in androgenetic alopecia (AGA). Kopexil (KPX), a minoxidil analog for AGA treatment, was successfully synthesized into MCCs with benzoic acid (BA) and salicylic acid (SA), yielding KPX-BA·HO cocrystal hydrate and KPX-SA·HO salt hydrate. The solid-state properties of the resulting MCCs were thoroughly characterized. Single-crystal analysis indicated that MCCs were stabilized by acid-aminopyrimidine heterosynthons. The KPX MCC powders were further formulated into dissolving microneedles (MNs). In vitro membrane diffusion tests demonstrated KPX MCCs encapsulated in MNs achieved a 1.86-fold and a 3.20-fold reduction in the amounts of KPX diffused compared to KPX·HO at 4 h. The diffusion of KPX MCCs was positively correlated with their solubilities, following the first-order kinetic model. With the absence of prior reports on KPX MCCs, these findings can inform the broader development of MCCs for APIs that have yet to be explored. The use of pharmaceutically accepted coformers, scalable fabrication methods, predictable release profiles, favorable biocompatibility, and painless self-application microneedle patches collectively offer a viable strategy for the potential clinical translation of this platform for AGA.
Overcoming size barriers in retinal gene therapy via lipid nanoparticle-mediated delivery of full-length eys DNA.
Goddaer S, De Coster E, Callens E … +7 more , Van Caenegem E, Van den Heule O, Collin RWJ, Peynshaert K, Van Nieuwerburgh F, Braeckmans K, Remaut K
Drug Deliv Transl Res · 2026 Jan · PMID 41606207 · Publisher ↗
Gene augmentation for inherited retinal diseases (IRDs) is constrained by the limited packaging capacity of viral vectors, rendering large genes such as EYS inaccessible to conventional delivery platforms. Here, we demon...
Gene augmentation for inherited retinal diseases (IRDs) is constrained by the limited packaging capacity of viral vectors, rendering large genes such as EYS inaccessible to conventional delivery platforms. Here, we demonstrate a non-viral lipid nanoparticle (LNP) strategy for the intracellular delivery and transcription of full-length EYS plasmid DNA (~ 11.6 kb), a gene implicated in autosomal recessive retinitis pigmentosa. An LNP formulation based on the ionizable lipid KC2 and DOPC was first optimized using an eGFP reporter construct, achieving high encapsulation efficiency and robust transgene expression in ARPE-19 cells. The same formulation encapsulating the EYS construct showed single-copy loading and structural stability in human vitreous, while confocal imaging and RT-qPCR verified functional delivery in retinal pigment epithelial (RPE) cell cultures. In an ex vivo bovine retinal explant, laser capture microdissection followed by RT-qPCR of the photoreceptor layer confirmed EYS mRNA expression after mimicking subretinal injection. This provides direct evidence of nuclear plasmid delivery in retinal tissue, which closely preserves the laminar structure and cellular composition of the human retina. To our knowledge, this is the first report of in vitro/ex vivo LNP-mediated delivery of a large (> 10 kbp) full-length IRD-relevant gene, underscoring the potential of LNPs for overcoming the size constraints of current gene therapies.
Stimuli-responsive nanocarriers for targeted mRNA therapeutics: a paradigm shift in mRNA delivery for biomedical applications.
Yadav N, Debnath N, Das S
Drug Deliv Transl Res · 2026 Jun · PMID 41593245 · Publisher ↗
Messenger RNA (mRNA) based therapeutics have emerged as a transformative modality with immense potential for treating infectious diseases, cancer, genetic disorders, and other complex conditions. Despite their promise, c...
Messenger RNA (mRNA) based therapeutics have emerged as a transformative modality with immense potential for treating infectious diseases, cancer, genetic disorders, and other complex conditions. Despite their promise, clinical translation has been challenged by mRNA's intrinsic instability, rapid degradation, and limited target specificity. The therapeutic value of mRNA lies in its ability to precisely modulate or restore protein expression, offering a versatile platform for personalized medicine. While conventional delivery approaches have yielded modest improvements, the integration of nanotechnology, particularly stimuli-responsive, nanoparticle-mediated systems, represents a breakthrough in overcoming these limitations. These advanced nanocarriers respond to both endogenous physiological triggers (such as pH shifts, redox gradients, reactive oxygen species, enzymatic activity, and hypoxic environments) and exogenous stimuli (including light, ultrasound, magnetic fields, and temperature changes), thereby enabling controlled, site-specific, and temporally regulated mRNA release. This dual responsiveness enhances therapeutic efficacy by improving mRNA stability, bioavailability, and minimizing off-target immune activation. This review highlights the design principles, mechanisms, and therapeutic applications of stimuli-responsive nanocarriers in mRNA delivery. It underscores recent innovations in nanoparticle engineering that address existing challenges and pave the way for next-generation precision medicine. Together, these advancements signal a paradigm shift in targeted mRNA therapy, offering new hope for treating previously intractable diseases.
Clinical translation of injectable hydrogels: from bioactive polymers to long-acting drug delivery systems.
Carballo-Pedrares N, Giménez VMM, Alonso MJ
Drug Deliv Transl Res · 2026 Jun · PMID 41571911 · Full text
Injectable hydrogels (IHs) have emerged as versatile biomaterials that enable localized therapy through minimally invasive delivery. Their in situ sol-gel transition supports sustained and targeted release of therapeutic...
Injectable hydrogels (IHs) have emerged as versatile biomaterials that enable localized therapy through minimally invasive delivery. Their in situ sol-gel transition supports sustained and targeted release of therapeutics, enhancing patient comfort and reducing dosing frequency. However, clinical translation remains limited due to challenges in achieving controlled degradation, ensuring long-term biocompatibility, scaling production, and meeting regulatory standards. Despite these hurdles, several IH-based formulations are progressing through clinical trials or have reached the market, underscoring their therapeutic potential. This review examines the major translational barriers and highlights recent advances that are accelerating the adoption of IHs in precision and personalized medicine.
Localized doxycycline delivery via polymeric nanoparticles anchored to electrospun PCL microfiber patch for MMP-2 inhibition in abdominal aortic aneurysm.
Bofill-Bonet C, Febas G, Artigues M … +5 more , Moreno-Jiménez I, Balà N, Martorell J, Borrós S, Fornaguera C
Drug Deliv Transl Res · 2026 Jan · PMID 41557116 · Publisher ↗
Doxycycline (DOXY) is a well-established antibiotic that has recently shown potential in inhibiting matrix metalloproteinase-2 (MMP-2), a key enzyme involved in the progression of abdominal aortic aneurysms (AAA). Howeve...
Doxycycline (DOXY) is a well-established antibiotic that has recently shown potential in inhibiting matrix metalloproteinase-2 (MMP-2), a key enzyme involved in the progression of abdominal aortic aneurysms (AAA). However, the controlled delivery of DOXY to the aneurysm site, with sustained release and minimal systemic exposure, remains a critical challenge in therapeutic development. To address this, we developed a targeted drug delivery platform based on polymeric nanoparticles (NPs), prepared from water-in-oil-in-water nano-emulsions, encapsulating DOXY and are covalently attached to electrospun ε-poly(caprolactone) (ε-PCL) microfibers. This system was designed to enable local, sustained drug release in the inner wall of aorta while preserving the mechanical properties of the aortic wall. The ε-PCL electrospun microfibers from the patch were first functionalized using oxygen cold plasma treatment, creating free radicals that enabled covalent bonding with chemical groups on the outer layer of DOXY-loaded poly(lactic-co-glycolic acid) (PLGA) NPs. This strategy allowed for robust immobilization of the NPs onto the microfibers surface, forming a composite system capable of localized and controlled drug release over time. Unlike traditional delivery approaches, this method ensures site-specific action of DOXY directly at the aneurysmal tissue, minimizing systemic circulation and reducing off-target toxicity. The platform not only provides a stable drug reservoir but also offers intrinsic biomechanical reinforcement, which is critical in AAA condition. This innovative delivery system represents a significant advance in the localized treatment of vascular disorders. It offers a biocompatible, biodegradable, and precisely targeted therapeutic approach, with potential to reduce the need for surgical intervention and limits the adverse effects associated with systemic drug administration. HIGHLIGHTS: - Novel polymeric Doxycycline loaded PLGA nanoparticles have been developed and result efficacious within hMMP-2 mitigation and collagen degradation in Abdominal Aortic Aneurysm condition. - Doxycycline loaded polymeric nanoparticles were covalently anchored to ε-Poly(caprolactone) electrospun microfibers via cold plasma-induced radical grafting, enabling sustained drug release for over 12 days. - Doxycycline-loaded nanoparticles released from microfibers efficaciously mitigate hMMP-2 in human in vitro models of Abdominal Aortic Aneurysm. - Doxycycline released from drug-coated electrospun ε-Poly(caprolactone) although efficacious does not allows time-control.
Correction: Assessment of AAV/polyketal chimeric nanoparticles for ocular gene transduction using an animal model.
Castro BFM, Lugin M, Guerra MCA … +5 more , Dias MF, Lee RT, Silva-Cunha A, Kwon YJ, Fialho SL
Drug Deliv Transl Res · 2026 Apr · PMID 41545811 · Publisher ↗
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3D-Printed gelatin patches for topical delivery of niacinamide and vitamin A: Bridging microstructure, in vitro release, and in vivo penetration.
Bom S, Prazeres P, Pinto PC … +2 more , Ribeiro HM, Marto J
Drug Deliv Transl Res · 2026 Jan · PMID 41545810 · Publisher ↗
The development of advanced topical delivery systems that enhance skin penetration and ensure controlled release of bioactives is a key focus in pharmaceutical research. Semi-solid extrusion 3D printing (SSE-3DP) has eme...
The development of advanced topical delivery systems that enhance skin penetration and ensure controlled release of bioactives is a key focus in pharmaceutical research. Semi-solid extrusion 3D printing (SSE-3DP) has emerged as a versatile technology for fabricating topical patches, allowing precise control over internal architecture to tailor release and penetration profiles. This research investigates the integration of niacinamide (Nia) and vitamin A-palmitate (VitA) into printable gelatin-based inks, employing both pre-printing rheological assessments and post-printing structural analyses-scanning electron microscopy (SEM), micro-computed tomography (micro-CT) and mechanical properties (tension and compression). Additionally, the study evaluates how variations in patch internal design affect the release kinetics and penetration profiles of Nia and VitA, utilizing both in vitro (Franz cells and Raman Microscopy, RM) and in vivo quantitative (Confocal Raman Spectroscopy, CRS) methodologies. Results indicated a significant correlation between in vitro and in vivo data. Additionally, RM provided valuable molecular-level insights, making it an effective in vitro tool for investigating skin retention. CRS in vivo highlighted different penetration behaviors: while Nia penetration was strongly influenced by the patch design (porous vs. occlusive: 20 min, 0.074 ± 0.027 mg/cm and 0.048 ± 0.022 mg/cm; 40 min, 0.084 ± 0.037 mg/cm and 0.052 ± 0.038 mg/cm), particularly after short application times, VitA penetration was highly dependent on the integrity of the skin barrier (normal vs. slightly compromised). Notably, this work introduced the first study to apply quantitative in vivo CRS to evaluate 3D-printed topical systems, highlighting the potential of SSE-3DP as a design-driven strategy for effective and personalized topical delivery.
A novel murine model of LITT for glioblastoma reveals tumor reduction, BBB permeabilization, and drug delivery via ThermoDox.
Athukuri P, Moreno K, McDonald MF … +8 more , Puentes A, Dei-Ampeh A, Marisetty A, Yang Y, Lee S, Latha K, Needham D, Rao G
Drug Deliv Transl Res · 2026 Jan · PMID 41540320 · Publisher ↗
Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for brain tumors that are recurrent or surgically inaccessible. We developed a murine model of LITT to investigate its effects on tumor burden,...
Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for brain tumors that are recurrent or surgically inaccessible. We developed a murine model of LITT to investigate its effects on tumor burden, immune activation, and delivery of heat-activated therapeutics. We engineered a preclinical LITT system using a 1064-nm laser coupled to a 400-μm fiber-optic probe. Orthotopic gliomas were established in the right frontal cortex of BL6 mice using luciferase-transduced glioma cells. Ten days post-implantation, mice were treated with LITT (0.45 or 0.75 W). Tumor response and blood-brain barrier (BBB) disruption were assessed using bioluminescence imaging (BLI), Evans Blue dye, and histology at 3, 7, and 14 days post-treatment. Immunofluorescence (IF) staining characterized immune cell activation. The distribution of doxorubicin released from intravenously administered Thermodox was also evaluated. LITT disrupted the BBB, enabling Evans Blue dye and doxorubicin penetration up to 4 mm from the probe. Tumor burden was reduced by LITT, as shown by decreased hypercellularity on H&E and reduced BLI signal, while sham-treated mice showed tumor progression. A reproducible ablation zone formed at the probe site. IF revealed increased IBA1 + macrophages and T cell infiltration in LITT-treated brains. Thermodox-derived doxorubicin distribution correlated with thermal diffusion and matched a Fickian perfusion model. We present a reproducible preclinical model of LITT that enables investigation of tumor ablation, immune modulation, and thermally triggered drug delivery. These findings support the use of LITT as a platform for combinatorial strategies in glioma treatment.
Genistein-loaded solid lipid nanoparticle in microneedle patch: potential for enhanced management of osteoporosis.
Shetty S, Jose J, Gopan G … +2 more , Aswani N, Dwivedi P
Drug Deliv Transl Res · 2026 Jan · PMID 41530578 · Publisher ↗
Microneedle patches, which are minimally invasive and have high patient compliance, offer a potential alternative for transdermal drug delivery, particularly in chronic diseases such as osteoporosis, which require consis...
Microneedle patches, which are minimally invasive and have high patient compliance, offer a potential alternative for transdermal drug delivery, particularly in chronic diseases such as osteoporosis, which require consistent long-term therapy. Genistein is an osteoprotective plant-derived isoflavone that suffers from poor aqueous solubility and low bioavailability, thereby limiting its medicinal value. In this study, a genistein-loaded solid lipid nanoparticles integrated with dissolving microneedles was developed for the management of osteoporosis. SLNs were prepared using glyceryl monostearate and Tween 80, and optimized by using a Box-Behnken design. The optimised formulation of SLNs (F3) was incorporated into dissolving microneedles. The developed dissolving microneedles were studied for various characterisations, and they featured uniform geometry, sharp, pointed edges, a drug delivery profile of 69.218 ± 3.64% at 8 h. Its anti-osteoporotic studies were carried out on 6 groups of Wistar albino rats, and studies showed that significant decrease in the creatinine level and osteoclast cells; on the other hand, a substantial increase in total protein, bone weight, hardness, thickness, and trabecular composition. A skin irritation test, which was performed, manifested the biocompatible, dermatologically safe quality of the developed dissolving microneedles. This microneedle platform, coupled with an optimised SLNs carrier, ensures a non-invasive controlled transdermal delivery, maximising genistein's osteogenic potency for the effective management of osteoporosis.
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