Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
Correction to: Rational design of lipid-based nanoparticles for targeted anticancer therapies.
Arenas-Moreira M, Ocaña A, Alonso-Moreno C … +1 more , Bravo I
Drug Deliv Transl Res · 2026 Apr · PMID 42024211 · Publisher ↗
Abstract loading — click title to view on PubMed.
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.
Fatriyah S, Nizardo NM, Saputri FC … +6 more , Jung H, Lee A, Mulyadi CA, Willie YBA, Marwah M, Ramadon D
Drug Deliv Transl Res · 2026 Apr · PMID 42020839 · Publisher ↗
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 pai...
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.
Advances in veterinary drug and vaccine delivery: from conventional delivery methods to innovative transdermal approaches.
Miranda-Muñoz KA, Tsai T, Powell JG … +1 more , Almodovar J
Drug Deliv Transl Res · 2026 Apr · PMID 42009974 · Publisher ↗
Veterinary drug delivery must balance efficacy, ease of administration, and animal welfare. Traditional methods, such as oral and injectable routes, pose challenges due to species-specific variations, stress during admin...
Veterinary drug delivery must balance efficacy, ease of administration, and animal welfare. Traditional methods, such as oral and injectable routes, pose challenges due to species-specific variations, stress during administration, and the need for repeated dosing. Emerging transdermal systems, particularly microneedle patches, offer a minimally invasive alternative that enhances drug absorption while reducing handling stress toward animals and improving compliance. Microneedle technology enables controlled and sustained drug release, making it particularly effective for pain management, vaccine delivery, and hormone therapies. By facilitating the transdermal administration of analgesics, microneedles deliver long-lasting pain relief with fewer interventions, improving the treatment of acute and chronic conditions in veterinary medicine. The use of biodegradable materials further enhances safety, eliminates the need for patch removal, and minimizes environmental impact. However, challenges such as species-specific skin permeability, formulation stability, and regulatory approval must be addressed for widespread adoption. This review examines the evolution of veterinary drug delivery, emphasizing microneedle-based technologies and their potential to improve pain management and therapeutic outcomes. By overcoming existing limitations, these systems could transform treatment approaches, simplify administration, and enhance overall animal care. Continued research and development will be essential for optimizing these technologies and expanding their applications in both clinical and agricultural settings.
Solid lipid microparticles-into-film delivering clobetasol: from buccal formulation design to pilot clinical study in patients with oral lichen planus.
Di Prima G, Mauceri ME, Coppini M … +4 more , La Mantia C, Mauceri R, Campisi G, De Caro V
Drug Deliv Transl Res · 2026 Apr · PMID 42009973 · Publisher ↗
Oral lichen planus is a chronic inflammatory disorder of the oral cavity, for which the therapeutic gold standard consists of the topical administration of corticosteroids, such as clobetasol-17-propionate (CLB). Nowaday...
Oral lichen planus is a chronic inflammatory disorder of the oral cavity, for which the therapeutic gold standard consists of the topical administration of corticosteroids, such as clobetasol-17-propionate (CLB). Nowadays, there are no commercially available pharmaceuticals intended for CLB delivery within the oral cavity. Then, in clinical practice, the drug is administered via magistral galenic preparations, formulated as adhesive semisolids. As they possess numerous drawbacks (e.g., limited contact time, poor patients' compliance, inaccurate dosing), the research is still focused on the development of suitable solid buccal drug delivery systems (BDDS). This work aims to: i) combine buccal film and lipid microsystem technologies, thus yielding an innovative composite BDDS and ii) preliminary assess its in vivo effectiveness. Solid Lipid Microparticles containing CLB were designed to possess a softening temperature close to body temperature, thereby facilitating the release of the drug in molecular form by fusion once applied. This lipid matrix, being tissue-affine, may also act as a penetration enhancer. Composite buccal films were then developed to facilitate microparticles administration, converting this powder into a solid mucoadhesive formulation. These Solid Lipid Microparticles-into-Film composites (SiF-composites) resulted homogeneous, highly mucoadhesive and capable of promoting CLB accumulation within the buccal mucosa. The best formulation was subjected to a pilot in vivo evaluation (5 patients per group receiving the SiF-composite or 0.05% CLB in Orafix) resulting in treatment adherence and a reduction in Thongprasom et al. scoring. The preliminary results obtained were extremely promising, thus suggest confirmation through a further larger, randomized double blind clinical trial.
Ginsenoside Rh2-modified liposomes for targeted delivery of Puerarin alleviate brain ischemia-reperfusion injury.
Wei M, Han W, Wu J … +5 more , Li Z, Tian M, Xu J, Chen X, Zhang Y
Drug Deliv Transl Res · 2026 Apr · PMID 42002677 · Publisher ↗
Brain ischemia poses a significant unmet medical need, demanding novel therapeutic approaches. Puerarin (Pue), despite its potential for treating brain disorders, suffers from poor blood-brain barrier (BBB) permeability...
Brain ischemia poses a significant unmet medical need, demanding novel therapeutic approaches. Puerarin (Pue), despite its potential for treating brain disorders, suffers from poor blood-brain barrier (BBB) permeability due to its low oil/water partition coefficient. To overcome this, we developed a novel ginsenoside Rh2-based liposome formulation (Rh2-Pue-LP) to enhance Pue delivery to the ischemic brain. A rat model of middle cerebral artery occlusion-reperfusion (MCAO/R) was established. Neurological deficits were evaluated using the Longa scoring system 24 h post-MCAO. After seven days of tail-vein administration of Rh2-Pue-LP, the following analyses were performed: TTC staining to assess cerebral infarct volume, HE and TUNEL staining to examine hippocampal histopathology, ELISA to quantify serum levels of IL-1β, TNF-α, and IL-6, and an LDH assay to measure serum lactate dehydrogenase activity reflecting cellular injury and pyroptosis, immunofluorescence to detect NLRP3 expression, and immunohistochemistry to evaluate the activation of JAK2-STAT3 and expression of inflammatory cytokines. Additionally, this study was conducted to further verify the targeting ability and safety of the formulation. Our results showed Rh2-Pue-LP treatment reduced infarct volume, improved neurological function, and decreased serum levels of inflammatory cytokines (IL-1β, TNF-α, IL-6), and markedly reduced serum LDH release Histological examination revealed better-preserved hippocampal neurons. Rh2-Pue-LP inhibited the JAK2-STAT3 signaling pathway and NLRP3 inflammasome expression, suppressing microglial activation and neuronal apoptosis. Additionally, Rh2-Pue-LP exhibited stronger brain targeting ability with no significant biotoxicity in vivo. Rh2-Pue-LP represents a promising strategy for treating ischemic stroke by enhancing Pue delivery and exerting potent neuroprotective effects.
Rapid synthesis of redox-responsive trithiocyanuric acid-based nanocarriers: in vitro multidrug resistance reversal and in vivo safety assessment.
Kopoleva E, Tsymbal SA, Kuchur OA … +14 more , Kulchanovskaya DS, Grishina AY, Pinova AA, Doroshenko IV, Romanov RI, Muslimov AR, Syuy AV, Ivkin DY, Kondratev VM, Rodimova S, Lepik KV, Bolshakov AD, Peltek OO, Zyuzin MV
Drug Deliv Transl Res · 2026 Apr · PMID 42002676 · Publisher ↗
Multidrug resistance (MDR) remains one of the principal challenges in cancer chemotherapy, necessitating new strategies to restore drug efficacy. In this study we developed and characterize a redox-responsive nanoplatfor...
Multidrug resistance (MDR) remains one of the principal challenges in cancer chemotherapy, necessitating new strategies to restore drug efficacy. In this study we developed and characterize a redox-responsive nanoplatform based on trithiocyanuric acid and polyethylene glycol (TTCA-PEG NPs) as a potential tool to overcome MDR and provide a biocompatible delivery system for conventional antitumor drugs. The platform was evaluated using doxorubicin (DOX), bleomycin (Bleo), or cisplatin (Cis) each pre-loaded into TTCA-PEG NPs and tested across three pairs of drug-sensitive and resistant cancer cell lines. TTCA-PEG NPs reduced drug resistance from 2- to 5 fold compared with free drug, consistent with the recovery of intracellular drug accumulation and cytotoxic activity. The nanoplatform was synthesized through a one-step process completed within one hour, offering substantial simplification compared with conventional redox-responsive systems. Mechanistic studies revealed that treatment induced G/M cell cycle arrest and apoptosis, confirming the restoration of the drugs' cytotoxic pathways in resistant cells. In vivo evaluation demonstrated a biocompatible profile, with no detectable hematopoietic, hepatic, renal, neurological, or cardiac toxicity at therapeutic doses. Pharmacokinetic studies showed that TTCA-PEG NPs modulated the rapid burst release of free Cis into a controlled, sustained-release profile, resulting in prolonged circulation and reduced systemic exposure. These findings present TTCA-PEG NPs as a biocompatible and adaptable redox-responsive platform. While in vivo efficacy studies are required to fully establish therapeutic utility, the current data regarding safety, pharmacokinetics, and in vitro MDR reversal suggest the platform is a promising candidate for further development.
Advanced modafinil-loaded transethosomes for brain targeting: development, ex-vivo permeation and radio-distribution evaluations.
Sayyed ME, Ahmed S, Attallah KM
Drug Deliv Transl Res · 2026 Apr · PMID 41996060 · Publisher ↗
Modafinil is a well-established wake-promoting agent with emerging applications as a cognitive enhancer; however, its clinical potential is constrained by poor aqueous solubility and suboptimal systemic absorption, limit...
Modafinil is a well-established wake-promoting agent with emerging applications as a cognitive enhancer; however, its clinical potential is constrained by poor aqueous solubility and suboptimal systemic absorption, limiting effective brain delivery. This study presents transethosomes as a hitherto unexplored nanocarrier for modafinil and combines design-driven formulation with nuclear imaging-based biodistribution. Transethosomal vesicles were prepared using the ethanol injection method and systematically optimized through a 2 factorial design employing Design-Expert software. Key formulation variables were investigated for their impact on EE%, PS, PDI, and ZP. Additionally, an in-vivo biodistribution and pharmacokinetic studies were conducted after labeling MOD with Technetium-99 m using sodium dithionite as a reducing agent. The optimized formulation achieved a high desirability value (0.919), superior EE% (85.87%), nanoscale PS (180.30 nm), and a negative ZP (- 42.60 mV), indicative of excellent vesicular stability. Morphological and FTIR analyses confirmed spherical vesicles, drug-excipient compatibility, and preservation of Modafinil's structure. In-vitro studies demonstrated a controlled biphasic release, supporting sustained drug availability, while stability assessments revealed no significant changes in vesicular characteristics over time. Ex-vivo studies highlighted markedly enhanced permeability, due to improved membrane fluidity and vesicle deformability from ethanol and the edge activator. The radiolabeling efficiency was high (92.18%), and it was stable for two hours. Biodistribution and pharmacokinetic studies confirmed significantly higher brain drug accumulation, elevated brain C (5.4%ID/g) and AUC, reduced T (10 min) and high relative bioavailability (424.3 ± 4.5%). Importantly, histopathological examination of nasal mucosa revealed normal architecture. Collectively, these findings establish transethosomes as a promising and safe nano-platform for advanced brain targeting. HIGHLIGHTS: Modafinil-loaded transethosomes were designed as nanovesicles for brain targeting. The optimized formulation showed spherical morphology, uniform size distribution, and strong drug-carrier compatibility. Stability studies confirmed preserved physicochemical properties throughout storage. Ex-vivo permeation revealed significantly enhanced mucosal drug transport versus plain modafinil dispersion. In-vivo radio-distribution unambiguously confirmed superior uptake into the brain and improved targeting efficiency when contrasted with the reference preparation.
An inhalable dry powder co-delivery system of ciprofloxacin liposomes and S-nitrosoglutathione for synergistic treatment of Pseudomonas aeruginosa biofilm-associated pulmonary infections.
Ran F, Chai G
Drug Deliv Transl Res · 2026 Apr · PMID 41996059 · Publisher ↗
Pseudomonas aeruginosa (PA) biofilm-associated chronic lung infections pose a significant therapeutic challenge due to the limited penetration and efficacy of conventional antibiotics. In this study, we developed an inno...
Pseudomonas aeruginosa (PA) biofilm-associated chronic lung infections pose a significant therapeutic challenge due to the limited penetration and efficacy of conventional antibiotics. In this study, we developed an innovative dry powder inhaler (DPI) formulation co-loading ciprofloxacin-encapsulated liposomes (CIP-Lips) and S-nitrosoglutathione (GSNO) using an ultrasonic spray-freeze-drying (USFD) technique. GSNO, a nitric oxide (NO) donor, promotes biofilm dispersion and induces bacterial phenotypic switching, thereby enhancing the accessibility of CIP-Lips to biofilm-embedded bacteria. Subsequently, CIP released from the liposomes exerts direct antibacterial activity. The combination of CIP-Lips and GSNO produces a synergistic "biofilm-disrupting and bactericidal" therapeutic effect, leading to effective biofilm eradication. The optimized DPI formulation exhibited satisfactory in vitro aerosol performance, with a fine particle fraction of 36.51 ± 0.49%, ensuring efficient lung deposition. In vitro evaluations further confirmed pronounced biofilm disruption and bactericidal efficacy. Furthermore, in a murine model of chronic pulmonary infection, the CIP-Lips/GSNO DPI significantly reduced the bacterial burden without observable systemic toxicity. This inhalable system represents a promising strategy for the treatment of PA biofilm-associated lung infections.
A dual-function rebamipide cubogel for enhanced ocular penetration and tear film restoration: optimization, safety, and in-vivo evaluation.
Salama M, Adel IM, Tag R … +1 more , Fares AR
Drug Deliv Transl Res · 2026 Apr · PMID 41984400 · Publisher ↗
Dry eye disease is a troublesome multifactorial ocular condition, affecting 5-50% of the population. Rebamipide is a mucin secretagogue with anti-inflammatory properties used for dry eye management, however, its efficacy...
Dry eye disease is a troublesome multifactorial ocular condition, affecting 5-50% of the population. Rebamipide is a mucin secretagogue with anti-inflammatory properties used for dry eye management, however, its efficacy is limited due to its poor aqueous solubility and low tissue permeation. This study aimed to formulate and optimize rebamipide-loaded cubosomes incorporated into a carboxymethyl cellulose gel to achieve a dual action of sustained drug release and enhanced corneal penetration. The proposed cubosomes were prepared via hot melt emulsification technique and optimized applying a 3 Box-Behnken design. The optimum cubosomes (particle size 173.6±10.89 nm, polydispersity index 0.349±0.04, zeta potential - 29.3±1.2 mV, and drug release 65.89±0.45% at 8 h) exhibited cubic morphology and physical stability for 90 days. Moreover, the rebamipide-loaded cubogel had a uniform spreadability with a shear-thinning, pseudoplastic rheological behavior, and an acceptable pH value for ocular use. Additionally, as per cell culture studies, the cubogel exhibited high safety profile (cell viability > 90%) and potent anti-inflammatory effect. Confocal scanning laser microscopy demonstrated a 2.64-fold increase in corneal tissue permeation of the rebamipide cubogel, as compared to the drug suspension. In-vivo pharmacodynamic study was performed and concluded with the added efficacy of incorporating rebamipide into cubogel form over drug suspension (16-fold rise in nitric oxide inhibitory action). Collectively, the dual-function rebamipide cubogel offers a safe and efficacious platform for dry eye management, integrating prolonged retention with synergistic mucin-stimulating and lubricating effects.
Fibrosis suppressive effect and mechanism of CaSR positive allosteric modulators/p-dioxanone copolymers.
Feng C, Liu Y, Zhang C … +3 more , Niu L, Dong J, Wang B
Drug Deliv Transl Res · 2026 Apr · PMID 41981360 · Publisher ↗
Fibroblast-to-myofibroblast transition (FMT) and resistance to apoptosis are central drivers of fibrosis. Here, we report that sustained release of Calcium Sensing Receptor (CaSR) positive allosteric modulators (L-Phe, L...
Fibroblast-to-myofibroblast transition (FMT) and resistance to apoptosis are central drivers of fibrosis. Here, we report that sustained release of Calcium Sensing Receptor (CaSR) positive allosteric modulators (L-Phe, L-Trp, and cinacalcet) from electrospun p-dioxanone copolymer membranes exerts potent, ligand-specific anti-fibrotic effects. All formulations activated Gq-coupled CaSR, evoking ER-Ca⁺ release and IP₃ generation. Differential recruitment of Gi yielded distinct cAMP/ROS signatures: cinacalcet (strong Gi bias) lowered cAMP and ROS levels, and suppressed AP-1, collagen-I and α-SMA expression; L-Trp (intermediate Gi) left cAMP unchanged while elevating ROS and inflammatory markers but nonetheless inhibited proliferation; L-Phe (weak Gi) raised cAMP, reduced ROS and fibrotic markers. Molecular docking confirmed Gi-coupling potency: cinacalcet (-125.4 kJ mol⁻) > L-Trp (-101.7 kJ mol⁻) > L-Phe (-75.5 kJ mol⁻). In a rat intestinal-adhesion model, cinacalcet and L-Phe membranes prevented adhesions and collagen deposition, whereas L-Trp only inhibited proliferation. Thus, these findings indicate that CaSR ligands tune fibroblast fate via Gi-biased receptor conformations and that ligand electrospun membranes constitute a versatile materials platform for precision antifibrotic therapy.
Pirfenidone-exosomes as innovative strategies for scarless tissue repair in wound healing.
Wang J, Sun C, Ho EA
Drug Deliv Transl Res · 2026 Apr · PMID 41973317 · Publisher ↗
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...
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.
Redefining long-acting injectables: the emerging role of extracellular vesicles in sustained drug delivery.
Mathlouthi S, Szczepanski A, Pesce C … +3 more , Malfanti A, Kuryk L, Garofalo M
Drug Deliv Transl Res · 2026 Apr · PMID 41968266 · Publisher ↗
Long-acting drug delivery systems (LADDS) have emerged as an effective strategy to overcome the limitations of conventional oral and parenteral therapies, enabling sustained drug exposure, reduced dosing frequency, and i...
Long-acting drug delivery systems (LADDS) have emerged as an effective strategy to overcome the limitations of conventional oral and parenteral therapies, enabling sustained drug exposure, reduced dosing frequency, and improved patient compliance. To date, clinically approved long-acting injectables (LAIs) predominantly rely on chemical platforms, including biodegradable polymeric depots, lipid-based formulations, and crystalline nanosuspensions. Although these systems have demonstrated significant clinical success, their performance is largely dictated by formulation-dependent physicochemical mechanisms and is often associated with challenges such as local tissue reactions, formulation instability, and limited flexibility in controlling release kinetics. In recent years, biologically derived carriers have gained increasing attention as next-generation long-acting delivery systems. Among these, extracellular vesicles (EVs) represent a unique class of endogenous nanocarriers with intrinsic stability, low immunogenicity and biologically driven interactions with tissues and cells, thereby positioning them as promising candidates for sustained drug delivery applications. This review summarizes current LAI technologies, highlighting the strengths and limitations of established chemical LAIs, and critically examines the emerging potential of EV-based injectable systems. Particular emphasis is placed on engineering strategies that enable EVs to acquire depot-like behavior, including hydrogel-based formulations and microneedle platforms that extend local retention and modulate release kinetics while preserving EV bioactivity. Finally, key challenges related to manufacturing scalability, reproducibility, regulatory standardization, and clinical translation of EV-based LAIs are discussed. This review outlines the opportunities and remaining barriers for translating EVs into clinically viable long-acting drug delivery applications. Overall, these considerations provide a framework for advancing the rational design and clinical translation of EV-based long-acting delivery platforms.
Chitooligosaccharide-based hydrogel microneedle for the effective transdermal delivery of vancomycin.
Ittisaf MM, Miah MS, Pritom MH … +4 more , Mahin NA, Montha S, Ali MA, Ahmed S
Drug Deliv Transl Res · 2026 Apr · PMID 41961464 · Publisher ↗
Hydrogel Microneedle Patches (HMNPs) are effective transdermal drug delivery systems designed to provide a minimally invasive and painless transfer of the incorporated payloads across the stratum corneum barrier. Herein,...
Hydrogel Microneedle Patches (HMNPs) are effective transdermal drug delivery systems designed to provide a minimally invasive and painless transfer of the incorporated payloads across the stratum corneum barrier. Herein, Chitooligosaccharide (COS) based hydrogel microneedles of four different concentrations (15%, 20%, 25% and 30% PEGDA) were developed using Polyethylene Glycol Diacrylate (PEGDA) and Carboxymethyl Chitosan (CMC) as crosslinkers and Vancomycin hydrochloride (COVAN) as the incorporated drug. Several characterization methods, such as Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), and Scanning Electron Microscopy (SEM), were performed before evaluating their efficacy as a transdermal therapeutic cargo delivery depot through mechanical testing, swelling ratio, drug release performance, and antibacterial activity. All of the tested formulations exhibited adequate compressive strength over 0.2 N per microneedle and effective penetration capabilities across the stratum corneum barrier. The 30% HMNP exhibited the highest swelling at 255% after 24 h, whereas the 25% HMNP provided the highest drug release at 83% after 48 h, indicating a Fickian diffusion-induced drug release mechanism. This was confirmed by fitting drug release data into mass transfer models, where all formulations except the 30% HMNP's drug release data fit the Korsmeyer-Peppas model. Except for the 20% HMNP, all HMNPs exhibited significantly greater antibacterial activity against a gram-positive bacterium, B.cereus, compared to vancomycin alone. Such efficacy establishes the HMNPs as potential transdermal drug delivery systems (TDDS) in the treatment of gram-positive bacteria-induced diseases such as cellulitis, folliculitis, etc.
Correction: Microneedle loaded with luteolin-colostrum-derived exosomes: a dropless approach for treatment of glaucoma.
Elsherbiny SA, El-Kamel AH, Bakr BA … +1 more , Heikal LA
Drug Deliv Transl Res · 2026 Apr · PMID 41957224 · Publisher ↗
Abstract loading — click title to view on PubMed.
In vivo evaluation of the anti-inflammatory efficacy of liposomes loaded with Echinacea purpurea roots extracts.
Vieira SF, Fonseca-Rodrigues D, Mendanha D … +6 more , Castro VIB, Pires RA, Reis RL, Pinto-Ribeiro F, Ferreira H, Neves NM
Drug Deliv Transl Res · 2026 Apr · PMID 41957223 · Publisher ↗
WHO ranked chronic inflammatory diseases as the most significant cause of death. The current therapeutic approach is the constant administration of clinically available anti-inflammatory drugs; however, this strategy pre...
WHO ranked chronic inflammatory diseases as the most significant cause of death. The current therapeutic approach is the constant administration of clinically available anti-inflammatory drugs; however, this strategy presents severe side effects. New entities derived from plants have shown their potential for developing safe and effective therapies. Particularly, Echinacea purpurea extracts have demonstrated strong anti-inflammatory properties. Therefore, dichloromethanolic extracts of E. purpurea roots (DE-R), rich in alkylamides, were used to produce an anti-inflammatory formulation. To increase therapeutic efficacy, DE-R were loaded into liposomes (LPs), which were also engineered to actively target M1 macrophages via surface functionalization with folic acid (FLPs). The developed formulations were homogeneous, with a mean particle size of ≈114 nm. The liposomes were cytocompatible at all tested concentrations and strongly reduced IL-6 production in LPS-stimulated macrophages. As expected, FLPs + DE-R were 6.3 times better than LPs + DE-R, and 9.7 times greater than free DE-R. The anti-inflammatory activity of free DE-R and DE-R-loaded FLPs was assessed in an experimental rat model of inflammation. A single intra-articular injection of the FLPs + DE-R promoted a significant reduction of edema, inflammatory pain, and immune cell infiltration, particularly of CD68 macrophages, as well as IL-6 expression. This formulation reduced synovial inflammation more efficiently than free DE-R. We also demonstrated that the developed formulation was safe, as no welfare changes or harmful toxicity to major organs were observed. Therefore, E. purpurea roots extracts loaded in liposomes can be used as a natural, innovative, and powerful new formulation to treat chronic inflammatory diseases.
Injectable thermoresponsive hydrogel scaffold for enhanced delivery of next-generation induced neural stem cells for treatment of glioblastoma.
Maue KM, Dau NC, King JL … +3 more , Thang M, Hingtgen SD, Benhabbour SR
Drug Deliv Transl Res · 2026 Apr · PMID 41957222 · Publisher ↗
Glioblastoma (GBM) remains a highly aggressive brain tumor with poor prognosis despite surgical resection and standard chemoradiation. Induced neural stem cell (iNSC)-based therapies offer a promising strategy owing to t...
Glioblastoma (GBM) remains a highly aggressive brain tumor with poor prognosis despite surgical resection and standard chemoradiation. Induced neural stem cell (iNSC)-based therapies offer a promising strategy owing to their inherent tumor-homing ability and capacity to deliver therapeutics selectively to the tumor site; however, their poor retention within the tumor resection cavity limits clinical potential. Herein, we evaluated next-generation tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-secreting iNSCs (hiNeuroS) in combination with a biodegradable, thermo-responsive chitosan hydrogel for localized and sustained delivery of high densities of hiNeuroS. Direct comparisons with first-generation iNSCs (hiNSCs) demonstrated that hiNeuroS achieved faster and more extensive tumor cell kill across multiple tumor-to-therapeutic cell ratios in both U87 and patient-derived GBM8 models. Injectable chitosan scaffolds supported stem cell densities up to 2 10⁷ cells/mL, maintained > 90% viability, preserved scaffold microstructure, and maintained rapid gelation at physiological conditions. Gravimetric analysis revealed stable 30-day mass change profiles, with minimal net mass loss indicating preserved scaffold integrity. Moreover, encapsulated hiNeuroS retained their migratory capacity and robust TRAIL secretion, inducing significant tumor cell death in both GBM models. Collectively, these findings demonstrate that hiNeuroS maintain functional potency in GBM and are compatible with scaffold-based delivery. This work provides a foundation for future in vivo studies to assess scaffold-mediated retention, persistence, and therapeutic efficacy in an established GBM mouse model, supporting the development of an injectable hydrogel platform for next-generation cell-based therapies for treatment of GBM and other malignant tumors.
Rational design of lipid-based nanoparticles for targeted anticancer therapies.
Arenas-Moreira M, Ocaña A, Alonso-Moreno C … +1 more , Bravo I
Drug Deliv Transl Res · 2026 Apr · PMID 41957221 · Publisher ↗
Targeted anticancer therapies, including monoclonal antibodies, antibody-drug conjugates, siRNA, small-molecule inhibitors, and PROTACs, offer precise treatments but face severe pharmacokinetic and biological barriers, s...
Targeted anticancer therapies, including monoclonal antibodies, antibody-drug conjugates, siRNA, small-molecule inhibitors, and PROTACs, offer precise treatments but face severe pharmacokinetic and biological barriers, such as poor bioavailability, limited tumor penetration, and off-target toxicity. While first-generation lipid-based nanoparticles (LBNPs) successfully utilized the enhanced permeability and retention (EPR) effect, relying exclusively on passive targeting is insufficient due to tumor heterogeneity. Therefore, this review provides an integrative analysis focused on the rational design of LBNPs. We systematically explore how the distinct structural complexities and biological barriers of each therapeutic modality strictly dictate specific LBNP design rules. The optimization of various nanocarriers-including liposomes, solid-lipid nanoparticles, and nanostructured lipid carriers-is discussed through customized lipid compositions, surface functionalization for active targeting, and the incorporation of ionizable lipids to overcome intracellular barriers like endosomal entrapment. Furthermore, these structural designs are correlated with optimal administration routes, and the impact of formulation methods is evaluated by contrasting traditional emulsification with advanced continuous platforms like microfluidics and supercritical fluid technology. Finally, the clinical landscape and translational challenges of approved and experimental nanomedicines are assessed. We conclude that the transition from bench to bedside is currently hindered less by preclinical efficacy and more by manufacturing and regulatory bottlenecks. Overcoming chemistry, manufacturing, and controls (CMC) challenges, ensuring robust industrial scalability, and establishing harmonized regulatory frameworks are critical priorities for the future clinical success of targeted nanomedicines.
Advances in carrier-free nanodrug delivery systems.
Liu JY, Zheng YY, Wang SY … +4 more , Bi YP, Sun MS, Hao JF, He YJ
Drug Deliv Transl Res · 2026 Apr · PMID 41952012 · Publisher ↗
Nanotechnology has propelled the development of nanodrug delivery systems (NDDS) with remarkable potential in disease diagnosis and therapy. Nevertheless, conventional NDDS relying on exogenous nano-carriers suffer from...
Nanotechnology has propelled the development of nanodrug delivery systems (NDDS) with remarkable potential in disease diagnosis and therapy. Nevertheless, conventional NDDS relying on exogenous nano-carriers suffer from intrinsic limitations, including suboptimal drug-loading capacity and biocompatibility issues. In this context, carrier-free nanodrug delivery systems (CFNDDS), constructed through the intrinsic self-assembly of therapeutic molecules, have emerged as a paradigm-shifting alternative. CFNDDS enables drug loading efficiency close to the theoretical maximum, while effectively avoiding carrier-associated toxicity, thereby maximizing drug efficacy. This review meticulously elucidates the fundamental driving forces that regulate CFNDDS self-assembly and summarizes innovative delivery strategies based on single-drug, dual-drug, multi-drug, and prodrug modalities. Furthermore, we provide a comprehensive survey of recent advancements in CFNDDS applications for treating various diseases, including cancer, fatty liver disease, osteoarthritis, atherosclerosis, fibrosis, and antibacterial infections. Analyzing the mechanism of action and application value of CFNDDS from multiple dimensions, perspectives, and levels provides a crucial theoretical basis for developing and researching the clinical use of drugs.
Microfluidic ocular formulation of voriconazole designed for hospital production.
Stinat L, Bonnin M, Gimel JC … +10 more , Gastebois A, Razafimandimby B, Tireau E, Lautram N, Dallerac D, Lefebvre G, Verron S, Calvignac B, Crauste-Manciet S, Lagarce F
Drug Deliv Transl Res · 2026 Jul · PMID 41949754 · Full text
Fungal keratitis is a serious corneal infection with a limited therapeutic panel. Voriconazole, an azole antifungal, has been shown to be effective against many of the fungal strains involved in this type of infection. T...
Fungal keratitis is a serious corneal infection with a limited therapeutic panel. Voriconazole, an azole antifungal, has been shown to be effective against many of the fungal strains involved in this type of infection. The absence of an ocular dedicated formulation on the market has led to the use of the sterile commercial cyclodextrin based formulation as a hospital preparation with some drawbacks. The aim of this study was to design a dedicated formulation for ocular delivery using oil-in-water nanoemulsion. A 0.4% voriconazole nanoemulsion was formulated with an oil and two surfactants, complying with the standards set by the authorities and literature. The nanoemulsion was produced using the phase inversion composition method. It was also formulated using microfluidic technology, suitable for hospital transposition. The mean droplets size was around 100 nm and zeta potential was negative. The pH and osmolality have been adjusted without destabilizing the nanoemulsion. Additionally, it was demonstrated that the formulation consists of two compartments: oil nanodroplets and residual micelles. Voriconazole was preferentially found in the micellar compartment. Finally, in vitro determination of minimal-inhibition-concentration tests were carried out on Aspergillus and Fusarium fungal species and compared to the 1% current hospital preparation. These tests showed that our formulation was no less effective than the hospital preparation.
Economic analysis of microneedle technology: cost-effectiveness, manufacturing scalability, and commercialization challenges.
Nguyen HX, Nguyen LT
Drug Deliv Transl Res · 2026 Apr · PMID 41946826 · Publisher ↗
Microneedle technology represents a promising advancement in transdermal drug delivery, offering painless administration, enhanced patient compliance, elimination of cold chain requirements, and self-administration capab...
Microneedle technology represents a promising advancement in transdermal drug delivery, offering painless administration, enhanced patient compliance, elimination of cold chain requirements, and self-administration capabilities. Despite extensive development with over 4,000 patents, commercial translation remains limited to 13 products, predominantly cosmetic applications. Economic evaluations demonstrate microneedle patches achieve cost-effectiveness at price points below $30 per dose. Operational savings range from $0.24-$0.61 per dose across vaccination scenarios (≥ 87% probability), driven primarily by labor costs, followed by wastage reduction and freight decreases. Australian analysis projects $108 million annual savings for influenza vaccination through complete substitution of conventional systems. Manufacturing economics reveal significant barriers, with production facility establishment requiring $5-20 million capital investment and clinical development costs ranging from $10-40 million. Administration costs represent 43-63% of total vaccination expenses versus 8-10% for cold chain, identifying labor efficiency as the primary economic driver. Self-administration requires ≥ 3% compliance increases to offset administration success reductions. Manufacturing costs range from $0.50-$5.00 per patch, depending on scale and polymer selection. Regulatory pathways remain incompletely defined, creating uncertainties that delay market entry and increase expenditures. Regulatory approval costs reach hundreds of thousands to millions of dollars, while no microneedle patches have received FDA approval. Microneedle market projections indicate 6.83-7.2% compound annual growth from 2025 through 2030, reaching $4.46 billion globally. This review synthesizes reports from cost-effectiveness studies, manufacturing economics, regulatory pathways, and market dynamics, providing quantitative cost-effectiveness thresholds, identifying economic barriers, and offering recommendations for technology development, regulatory optimization, and market positioning to facilitate the clinical application of microneedle products.
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