Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
Dual-drug nanostructured lipid carriers of spironolactone and 2-deoxy-D-ribose for targeted follicular delivery in androgenetic alopecia.
Kayal P, Mishra MK, Jawahar N
Drug Deliv Transl Res · 2026 May · PMID 42218358 · Publisher ↗
Androgenetic alopecia (AGA) is a multifactorial condition driven by dihydrotestosterone (DHT)-induced follicular miniaturization and reduced perifollicular angiogenesis. Existing treatments such as finasteride, minoxidil...
Androgenetic alopecia (AGA) is a multifactorial condition driven by dihydrotestosterone (DHT)-induced follicular miniaturization and reduced perifollicular angiogenesis. Existing treatments such as finasteride, minoxidil, and dutasteride often show limited efficacy and systemic side effects like sexual dysfunction or cardiovascular issues, necessitating targeted approaches. The present study developed dual-drug nanostructured lipid carriers (NLCs) co-delivering spironolactone (SL), an anti-androgen, and 2-deoxy-D-ribose (2dDR), a pro-angiogenic agent, for synergistic follicular regeneration. NLCs were prepared by the hot microemulsion method, incorporating stearic acid as a solid lipid and fenugreek oil as a liquid lipid, with Span 80/Tween 80 surfactants. A Central Composite Design (CCD) was optimised to achieve minimal particle size and optimal zeta potential by varying lipid ratios and surfactant levels. The formulations were characterized by particle size analysis and zeta potential measurements, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and in vitro drug release kinetics. Cytotoxicity and dihydrotestosterone (DHT)-protection assays were performed using human dermal papilla cells (hDPCs). Optimized SL-2dDR NLCs exhibited a particle size of 343.03 ± 9.0 nm, a PDI of 27.97 ± 2.84%, and a zeta potential of -20.13 ± 0.40 mV. Entrapment efficiency reached 99.00 ± 0.5% for SL and 98.75 ± 0.7% for 2dDR. DSC and XRD confirmed amorphous drug dispersion, while SEM revealed irregular, porous morphology favorable for follicular adhesion. In vitro release followed Higuchi kinetics for SL (R = 0.994) and Hixson-Crowell for 2dDR (R = 0.985). MTT assays demonstrated concentration-dependent cytoprotection against DHT-induced cytotoxicity, maintaining 82% cell viability at 50 µg/mL. The dual-drug NLC system represents a promising targeted therapy for AGA, combining anti-androgenic and pro-angiogenic mechanisms while minimizing systemic exposure.
Strategies for engineering biomimetic lipoproteins to improve drug delivery efficiency and tumor therapy.
He Y, Yin N, Zhang Z … +2 more , Lu GL, Wen J
Drug Deliv Transl Res · 2026 May · PMID 42213349 · Publisher ↗
Cancer treatment remains limited by key challenges, including poor drug biodistribution, restricted tumor penetration, and severe systemic toxicity. Lipoprotein nanoparticles (LPNs) have emerged as promising platforms fo...
Cancer treatment remains limited by key challenges, including poor drug biodistribution, restricted tumor penetration, and severe systemic toxicity. Lipoprotein nanoparticles (LPNs) have emerged as promising platforms for drug delivery, addressing these obstacles. Their inherent biocompatibility, small size, and natural ability to interact with specific cellular receptors make them ideal candidates for targeted cancer therapy. This review presents recent advances in the design of LPNs to improve the precision and efficiency of anti-tumor drug delivery. We investigate how these smart nanoparticles enhance the therapeutic performance of three primary treatment modalities: chemotherapy, immunotherapy, and emerging nucleic acid-based therapies. This comprehensive review summarizes current strategies in the field and offers forward-looking insights into future innovations in LPN drug delivery systems (DDSs) for cancer therapy.
Safety evaluation of a novel progesterone vaginal ring (PVR) for luteal phase support: SARA trial.
Stadtmauer LA, Schnell VL, Park JK … +4 more , Slater CC, Foster ED, Grover SA, Heiser PW
Drug Deliv Transl Res · 2026 May · PMID 42213348 · Publisher ↗
After manufacturing changes, the safety and tolerability of the progesterone vaginal ring (PVR) was compared to findings from the similarly designed phase 3 trial. This prospective, open-label, single-arm, multi-center U...
After manufacturing changes, the safety and tolerability of the progesterone vaginal ring (PVR) was compared to findings from the similarly designed phase 3 trial. This prospective, open-label, single-arm, multi-center U.S. trial was conducted with women with tubal, idiopathic, male factor, ovulatory dysfunction, or endometriosis-linked infertility. Women underwent ovarian stimulation with highly purified human menotropin 225 IU/day in a standardized long agonist protocol. Weekly administration of PVR started the day after oocyte retrieval (OR), followed by ICSI and fresh blastocyst transfer, and continued for up to 10 weeks. The primary endpoint was spontaneous abortion rate, defined as 2 positive β-hCG tests and an empty intrauterine gestational sac or lacking a fetal heartbeat, or the absence of a viable fetus up to 12 weeks after OR. 254 women were treated with PVR at 14 sites July 2018-July 2019 (mean age 30.8 years, BMI 26.5 kg/m, AMH 2.8 ng/mL, FSH 7.0 mIU/mL). Adverse events occurring in ≥ 5% of the population included nausea (8.7%) and headache (5.1%). Incidence of predefined vaginal/cervical adverse events was 2.0%. Fresh embryo transfer was performed in 243 subjects (95.7%). The spontaneous abortion rate was 7.4%, with the upper bound of the 95% confidence interval (11.5%) below the predefined threshold of 15.0%. Clinical pregnancy rates 10 weeks post OR were 43.2%. This trial established a safety bridge between PVR produced via enhanced manufacturing processes and the legacy PVR, with comparable rates of spontaneous abortion. Weekly administration of PVR was well-tolerated with good pregnancy outcomes.Trial registration: NCT03565211 (https://clinicaltrials.gov/study/NCT03565211), registration June 21, 2018, first enrollment July 26, 2018.
Oral capsule administration of biomacromolecules that achieves bioavailability and pharmacokinetics comparable to subcutaneous injection in dogs - the BIONDD technology.
Skak N, Mertz N, Piwon N … +5 more , Olsen MR, Caffarel-Salvador E, Brayden DJ, Østergaard J, Lindhardt K
Drug Deliv Transl Res · 2026 May · PMID 42207426 · Publisher ↗
Biomacromolecules including peptides, proteins, antibodies, and gene medicines, comprise important classes of therapeutics in treating disease. A drawback of biologics is their inconvenient route of administration, as th...
Biomacromolecules including peptides, proteins, antibodies, and gene medicines, comprise important classes of therapeutics in treating disease. A drawback of biologics is their inconvenient route of administration, as they are mostly injected. Most patients prefer the oral administration route over injections. To accommodate this need, we developed the BIONDD technology, which is an oral administration device for biomacromolecules contained in a standard 00 or 0-sized capsule. Upon ingestion and actuation in the stomach, the macromolecule is delivered from the cavity of the device's spike into the gastric wall, from where it migrates to the blood vessels. Using 0.4 mg liraglutide as a model peptide, a short T and a relative oral bioavailability of 119% compared to subcutaneous administration were achieved over time after oral administration of the BIONDD capsule to dogs. The pharmacokinetic data from the large animal studies obtained provides proof-of-concept for a convenient oral delivery device for biologics.
From prototype to veterinary patient: a pharmacokinetic clinical trial of 3D-printed pimobendan tablets in beagle dogs.
Leão J, Winck VL, Barnet LS … +12 more , de Lima Junior JR, Bonfim IV, Fernandes AJB, de Jesus ILR, de Lima Monzato G, da Silva MP, da Silva MEC, Barreto F, Scott FB, Cid YP, de Andrade DF, Beck RCR
Drug Deliv Transl Res · 2026 May · PMID 42184094 · Publisher ↗
Pimobendan (PBD) is widely used to manage canine heart failure; however, commercially available formulations present limitations such as restricted dose flexibility and large tablet sizes, which may compromise long-term...
Pimobendan (PBD) is widely used to manage canine heart failure; however, commercially available formulations present limitations such as restricted dose flexibility and large tablet sizes, which may compromise long-term treatment individualisation. Three-dimensional (3D) printing offers a promising alternative by enabling customisable veterinary formulations. This study presents the first in vivo pharmacokinetic and clinical evaluation of 3D-printed PBD tablets (printlets) specifically designed for and administered to dogs. Printlets containing 2.5 mg of PBD were produced by semisolid extrusion 3D printing and compared with the commercial formulation Vetmedin. Both formulations were characterised for weight, dimensions, drug content, and in vitro dissolution. They were orally administered to healthy Beagle dogs at a single dose of 0.2 mg/kg. Plasma PBD concentrations were quantified by LC-MS/MS, and pharmacokinetic parameters were determined by non-compartmental analysis. The 3D-printed printlets were safely administered, and no adverse effects were observed during the study. The pharmacokinetic evaluation demonstrated systemic exposure following oral administration of the 3D-printed formulation according to their sustained release profile, showing differences in absorption profiles compared with the commercial formulation. Overall, this study provides in vivo evidence supporting the feasibility of semisolid extrusion 3D printing for the preparation of veterinary PBD dosage forms and highlights the potential of digital manufacturing technologies for individualized veterinary therapy.
Low dose intranasal nestorone self-emulsifying drug delivery system promotes neuroprotection in experimental stroke through modulation of glial cells.
Meirinho S, Ferreira SA, Diniz C … +10 more , Alves G, Zhang S, Kumar N, Sitruk-Ware R, Di G, Navarro-Oviedo M, Pradillo JM, Lizasoain I, Baltazar G, Santos AO
Drug Deliv Transl Res · 2026 May · PMID 42177349 · Publisher ↗
Ischemic stroke is a leading cause of disability worldwide, with current therapies mainly focused on clot fibrinolysis rather than neuroprotection. Nestorone (NES), a highly selective progesterone receptor agonist, has s...
Ischemic stroke is a leading cause of disability worldwide, with current therapies mainly focused on clot fibrinolysis rather than neuroprotection. Nestorone (NES), a highly selective progesterone receptor agonist, has shown neuroprotective potential in experimental stroke. However, NES exhibits poor water solubility and high hepatic first-pass metabolism, limiting its oral bioavailability, which motivated us to develop new lipid-based NES formulations for nose-to-brain delivery. With that rationale, a nanoemulsion (NE) and a self-microemulsifying drug delivery system (SMEDDS) were herein evaluated for NES intranasal delivery post-stroke in mice. NES-loaded SMEDDS and NE aqueous dispersions showed highly homogeneous droplet sizes of approximately 20 and 90 nm. NES permeation across the MucilAir™ model was significantly higher with the NE, which also demonstrated excellent in vitro safety. The SMEDDS decreased resazurin reduction, induced a small increase in LDH release, and caused a transient TEER decrease (< 100 Ω·cm²) that recovered within 4 days. In mice, both intranasal formulations produced higher and faster plasma and brain NES Cmax values (tmax 5 min) compared with subcutaneous administration. Intranasal SMEDDS achieved the highest brain Cmax and significantly greater brain/plasma NES concentration ratios. A single low NES-SMEDDS intranasal dose administered 1 h after stroke induction reduced infarct volume by 27% compared with saline (7.55 ± 0.99% vs. 10.33 ± 0.43%) and improved locomotor asymmetries. This effect was correlated with a less reactive astrocyte and microglia morphology at 48 h after ischemia. These results highlight intranasal NES-SMEDDS as a promising neuroprotective strategy warranting further preclinical and clinical investigation.
Preserving the gut microbiome: hydrogel-forming microneedle delivery of tetracycline reduces gut microbiome disruption compared to oral administration.
Kelly SA, Zhao L, Nzakizwanayo J … +9 more , Rodgers AM, Thompson TP, Lee AJ, McCarthy HO, McGrath JW, Ingram RJ, Jones BV, Gilmore BF, Donnelly RF
Drug Deliv Transl Res · 2026 May · PMID 42177348 · Publisher ↗
Antibiotics cause significant gut microbiome dysbiosis, particularly when administered orally. This contributes to antimicrobial resistance (AMR) and is associated with myriad health conditions. Novel drug delivery strat...
Antibiotics cause significant gut microbiome dysbiosis, particularly when administered orally. This contributes to antimicrobial resistance (AMR) and is associated with myriad health conditions. Novel drug delivery strategies that minimize gut exposure while maintaining therapeutic efficacy are urgently needed. This study aimed to evaluate whether a novel transdermal system could reduce gut microbiome disruption compared to oral delivery. Sprague-Dawley rats received a single tetracycline dose via oral gavage, IV injection, or hydrogel-forming microneedle patch. Faecal samples were collected longitudinally and analysed using 16 S rRNA gene sequencing. Oral tetracycline caused the greatest disruption to gut microbiota. Compared to the timepoint immediately prior to treatment (Day 5a), peak dysbiosis was observed at Day 7. The Firmicutes: Bacteroidetes ratio was significantly reduced following oral and IV tetracycline therapy, but not following microneedle administration. The most significant reductions in alpha and beta diversity at Day 7 were observed in the oral group. Differential abundance analysis showed oral treatment resulted in the highest number of depleted and enriched taxa. The microbiome-sparing effect of microneedle delivery was consistent across all analytical measures, offering a promising strategy to preserve host microbiome health. This minimally invasive approach represents a clinically viable alternative to oral and IV antibiotic administration.
Lifitegrast-eluting contact lens for dry eye disease: sustained release, enhanced ocular bioavailability, and robust in vitro-in vivo correlation.
Li Y, Zhou K, Yin X … +3 more , Shi F, Cheng Y, Zhao Y
Drug Deliv Transl Res · 2026 May · PMID 42174341 · Publisher ↗
Dry eye disease (DED) severely impacts patients' quality of life. Conventional treatments like lifitegrast eye drops face challenges of low bioavailability and adverse effects. This study developed lifitegrast-eluting co...
Dry eye disease (DED) severely impacts patients' quality of life. Conventional treatments like lifitegrast eye drops face challenges of low bioavailability and adverse effects. This study developed lifitegrast-eluting contact lenses (DeCLs) to enhance ocular drug delivery. Three DeCLs formulations (DeCLs-1: 0.2 mg, DeCLs-2: 0.3 mg, DeCLs-3: 0.6 mg) were prepared via soaking method. In vitro release studies using artificial tears flowing through a microfluidic chamber at controlled rates (0.15 ~ 0.30 mL/min) demonstrated sustained drug release profiles that were dependent on the flow rate. Functional evaluations confirmed DeCLs maintained optical clarity, diopter, mechanical integrity, and ion permeability comparable to blank lenses, with no significant swelling changes. Ex vivo studies in rabbit eyes revealed 50 ~ 60% cumulative drug release over 8 h, with DeCLs-2 following zero-order kinetics (R = 0.99725). At a dosage of 0.3 mg, DeCLs demonstrated comparable tear exposure (AUC) to that of eye drops administered at a dose of 1.0 mg. In vivo pharmacokinetics showed prolonged mean residence time of the DeCLs versus eye drops (p < 0.01), alongside reduced peak-to-trough fluctuations (> 99% lower). When the flow rate in the microchamber was set at 0.15 mL/min, DeCLs-1, DeCLs-2, and DeCLs-3-particularly DeCLs-2-demonstrated excellent in vitro-in vivo correlation (r = 1.00000). These findings demonstrate that DeCLs represent a promising therapeutic approach for DED, providing sustained drug delivery, reduced side effects, and improved patient compliance. Furthermore, the novel in vitro release model developed in this study, which establishes strong in vitro-in vivo correlation, paves the way for more ethical pharmaceutical research by potentially reducing reliance on animal testing.
Accelerating wound healing rates with Cucurbita pepo leaf extract loaded electrospun poly(methyl methacrylate)/Halloysite/Chitosan/CaCO₃ composite nanofibers through in vitro and in vivo assessments.
Abdelazim EB, Aly SH, H El-Moslamy S … +7 more , Mohamed HH, Abdul-Baki EA, Shakweer MM, Eissa NG, Kamoun EA, Elsabahy M, Salim SA
Drug Deliv Transl Res · 2026 May · PMID 42171943 · Publisher ↗
Cucurbita pepo leaf extract (CPE) was incorporated into electrospun poly(methyl methacrylate)/ halloysite/chitosan/CaCO₃ (PMMA/Hal/CS/CaCO₃) composite nanofibers to develop a novel biomaterial for accelerating wound heal...
Cucurbita pepo leaf extract (CPE) was incorporated into electrospun poly(methyl methacrylate)/ halloysite/chitosan/CaCO₃ (PMMA/Hal/CS/CaCO₃) composite nanofibers to develop a novel biomaterial for accelerating wound healing rates. The different nanofibrous scaffolds were successfully fabricated and characterized through scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). SEM analysis revealed uniform, smooth nanofibers, while FTIR and XRD confirmed the integration of CPE into nanofiber matrix, indicating an amorphous structure and effective dispersion of the extract. In vitro agar well-diffusion and antibiofilm assays revealed that the optimized formulation exhibited potent antimicrobial activity against wound-associated pathogens. The nanofibers composite based on PMMA provides structural stability, while Hal enhances mechanical properties and cell adhesion. Additionally, CS contributes to biodegradability and moisture retention, both of which are essential for effective wound healing. Furthermore, the inclusion of CPE offers additional antimicrobial benefits, further promoting the wound healing process. In vivo studies confirmed the wound-healing potential of the optimal loaded scaffold, with a 99.9% healing rate achieved by day 14. In vivo studies further demonstrated that CPE-loaded nanofibers significantly enhanced wound closure compared to untreated controls, likely due to the synergistic effects between CPE and PMMA/Hal/CS/CaCO₃ matrix. Histological analysis revealed increased macrophage infiltration, neovascularization, and fibroblast proliferation by day 7. Overall, these findings underscore the potential of incorporating natural bioactive compounds into electrospun nanofibers to develop biocompatible, eco-friendly antimicrobial materials for advanced wound-healing applications.
Enhanced subcutaneous delivery of antibody-drug conjugates with recombinant human hyaluronidase PH20: pharmacokinetics and tolerability in minipigs.
Nolan RP, Connor RJ, Printz MA … +6 more , Wang Y, Nekoroski T, Liu L, Wahl C, Theuer C, Kang DW
Drug Deliv Transl Res · 2026 May · PMID 42171942 · Publisher ↗
Subcutaneous (SC) administration of therapeutic antibodies offers advantages over intravenous (IV) delivery, including improved patient convenience and a pharmacokinetic (PK) profile characterized by lower peak plasma co...
Subcutaneous (SC) administration of therapeutic antibodies offers advantages over intravenous (IV) delivery, including improved patient convenience and a pharmacokinetic (PK) profile characterized by lower peak plasma concentrations without affecting overall exposure. These benefits may extend to antibody-drug conjugates (ADCs), but development has been limited by concerns that cytotoxic payloads could persist at the SC injection site, causing local tissue toxicity. This study evaluated the local tolerability and PK of SC administration of two marketed ADCs containing camptothecin payloads-sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-Dxd)-in miniature pigs, with and without recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that facilitates rapid dispersion and absorption. Across injection volumes of 1-20 mL, rHuPH20 improved injection performance, reduced swelling and back-leakage and resulted in an absence of adverse histologic changes. SC delivery with rHuPH20 increased systemic exposure (AUC) of total ADC and payload by 33-54% compared to SC without rHuPH20, reaching 52-80% of the IV AUC while maintaining substantially lower C values (25-39% of IV). In skin tissue, rHuPH20 reduced local retention of ADC components by 41-87%, indicating enhanced dispersion and accelerated absorption. These findings demonstrate that rHuPH20 enables safe and efficient SC delivery of ADCs in an animal model that closely reflects human SC tissue architecture and lymphatic drainage, improving systemic bioavailability and local tolerability. The resulting PK profile may mitigate C-driven ADC toxicities and optimize dosing of ADCs with narrow therapeutic windows.
Antimicrobial and regenerative copper-doped hybrid biomaterials for bone infection treatment.
Campodoni E, Bernardoni S, Granata V … +7 more , Vicinelli G, Panocchia A, Liberati F, Possetti V, Inforzato A, Sobacchi C, Sandri M
Drug Deliv Transl Res · 2026 May · PMID 42162538 · Publisher ↗
The bone tissue is endowed with intrinsic regenerative capacity. This is compromised in cases of major alterations like in trauma, surgical removal of cancer lesions, and infections. Osteomyelitis (OM) is an infectious d...
The bone tissue is endowed with intrinsic regenerative capacity. This is compromised in cases of major alterations like in trauma, surgical removal of cancer lesions, and infections. Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the gram-positive bacterium Staphylococcus aureus and characterized by extensive tissue remodelling and inflammation. Local and systemic antimicrobial treatments are the standard of care; however their efficacy is often limited by immune-mediated vascular damage and biofilm formation. Antimicrobial-loaded biomaterials offer a promising alternative. In this regard, hybrid scaffolds made of hydroxyapatite nanocrystals grown on collagen fibers and mimetic of bone extracellular matrix has already demonstrated to support cell functions and resorb over time. Also, they can be doped with bioactive and antimicrobial ions and release them in a controlled and sustained manner during scaffold degradation and tissue regeneration. In this study, we incorporated Cu²⁺-doped hydroxyapatite into collagen scaffolds (Col/CuHA) with the aim of developing a biomaterial capable at a time to prevent/treat bone infections and promote tissue regeneration. These matrices recapitulated the architecture of bone tissue and released Cu²⁺ ions with bactericidal activity towards a biofilm-forming isolate of Staphylococcus aureus. In vitro experiments in conditions mimicking dynamic fluid exchanges allowed identification of optimal Cu²⁺ loads with balanced antimicrobial activity and cytocompatibility. In vivo preliminary observations from a murine model of ectopic scaffold implantation suggested that these biomaterials can be integrated in the host tissue, thus further corroborating their biocompatibility with the applied loads of Cu. Our results point to Col/CuHA scaffolds as promising candidates for the prevention and/or treatment of osteomyelitis and the promotion of bone repair, and suggest that they might provide an innovative alternative to conventional antibiotic-based strategies.
Revisiting the lipid ratio in lipid nanoparticles: A comparison of OFAT and design of experiments approaches.
Forrester J, Vaughan E, Knappett BR … +1 more , Perrie Y
Drug Deliv Transl Res · 2026 May · PMID 42149348 · Publisher ↗
Despite the clinical success of lipid nanoparticles (LNPs), formulation optimisation remains dominated by inherited lipid ratios and screening approaches that fail to capture the combined influence of composition and man...
Despite the clinical success of lipid nanoparticles (LNPs), formulation optimisation remains dominated by inherited lipid ratios and screening approaches that fail to capture the combined influence of composition and manufacturing process. In this study, one-factor-at-a-time (OFAT) and Design of Experiments (DoE) strategies were applied to investigate how lipid molar ratio influences critical quality attributes (CQAs) and mRNA expression. In addition, manually executed and automated microfluidic manufacturing methods were compared to assess their impact on formulation-performance relationships. Across all strategies, multiple formulations beyond the standard molar ratio achieved comparable physicochemical properties, including particle size < 120 nm, low polydispersity index (PDI < 0.2), and high encapsulation efficiency (> 75%). Differences in CQAs and expression profiles were observed between manually and automated microfluidic manufactured DoE formulations, indicating that both composition and process conditions influence formulation performance. DoE analysis revealed non-linear and process-dependent relationships between lipid composition and CQAs, with limited predictive capability within the explored design space, particularly for biological outputs. Comparison of OFAT and DoE datasets demonstrated that while OFAT identifies directional trends within a constrained design space, DoE provides broader insight into interaction effects and formulation trade-offs. Overall, these findings demonstrate that the conventional lipid ratio represents a robust but not necessarily optimal formulation and support a shift towards context-dependent, design-space-driven optimisation of LNP systems.
Chemotherapeutic efficacy of nano formulation capecitabine@SNPs and gamma radiation: a novel metronomic approach for breast cancer treatment.
Ghanim MI, Abdelrahman IY, Kelany AK … +3 more , Askar MA, Gharib M, Abdelhakim HK
Drug Deliv Transl Res · 2026 May · PMID 42141305 · Publisher ↗
Despite the prevalence of various infectious and pandemic diseases worldwide, cancer remains the leading cause of death. Clinical approaches for treating cancer vary depending on the tumor type and aggressiveness, includ...
Despite the prevalence of various infectious and pandemic diseases worldwide, cancer remains the leading cause of death. Clinical approaches for treating cancer vary depending on the tumor type and aggressiveness, including surgery, chemo-, radio-, immune- and hormone therapies. However, the efficacy of these treatments is hindered by the high mortality rate during chemotherapy and radiotherapy, primarily due to severe side effects.This experimental study was conducted on 40 female Sprague-Dawley (SD) rats (n=8). A metronomic treatment strategy was employed using intraperitoneal administration of a small dose of capecitabine loaded onto silica nanoparticles (Cap@SNPs) (377mg/kg) once weekly for a month, either singly or in combination with a low dose of gamma ionizing radiation (IR) (0.5 Gy/5 days) over six sessions, against a 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinoma model in SD rats. The antitumor effect of Cap@SNPs and/or γ-radiation was assessed by tumor volume measurements, survival analysis, biochemical and haematological parameters and gene expression profiling of selected apoptotic and anti-apoptotic genes. Cell cycle phase distribution, apoptotic cells (Annexin V) and the expression of some immunomodulatory proteins were analyzed by flow cytometry. Histopathological examination was performed using hematoxylin and eosin (H&E) staining. The expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) proteins in mammary tissue was assessed by immunohistochemistry (IHC). The initial tumor volume across all groups was 32.8 ± 1.8 mm, reaching 86 ± 1.9 mm in the positive control at Day 30 but only 5.3 ± 0.5 mm in the Cap@SNPs + IR group. The death rate decreased from 75% in the positive control to 12.5% in the combined-treated group. Gene expression analysis revealed the downregulation and upregulation of the anti-apoptotic gene (Bcl2) and the apoptotic genes (Bax, Fas and Caspase-8), respectively, in the combination therapy. Flow cytometric analysis showed cell cycle arrest at the G1 phase and increased early apoptosis in the combined-treated group. The findings were verified by histopathological examination and immunohistochemical analysis of mammary tumor tissues. In conclusion, administration of a small capecitabine dose via silica nanoparticle delivery, along with fractionated radiotherapy, achieved substantial tumor regression, improved survival and effective cell-cycle arrest in mammary tumor-bearing rats. These findings support the integration of metronomic chemotherapy with nanoscale drug delivery systems and fractionated radiotherapy as a promising multimodal strategy to enhance anti-tumor efficacy, reduce dose-related toxicity and ultimately improve therapeutic outcomes.
Rheology-driven penetration dynamics of needle-free jet injection in ex vivo porcine tissue.
Imran JH, Kim JK
Drug Deliv Transl Res · 2026 May · PMID 42135551 · Publisher ↗
Needle-free jet injectors offer promising capabilities for drug delivery; however, achieving precise, depth-targeted penetration remains a significant challenge due to the complex interplay between formulation rheology a...
Needle-free jet injectors offer promising capabilities for drug delivery; however, achieving precise, depth-targeted penetration remains a significant challenge due to the complex interplay between formulation rheology and tissue biomechanics. This complexity precludes the use of a single equation applicable across diverse fluid classes. To address this issue, the present study employs high-speed deep tissue imaging of ex vivo porcine skin to compare the penetration behaviors of Newtonian, non-Newtonian, and protein-based formulations. Furthermore, a conceptual, data-driven prediction framework is introduced to complement scenarios where unified analytical modeling proves inadequate. High-speed near-infrared imaging, combined with optical tissue clearing techniques, was used to capture the microsecond-scale dynamics of the penetration of glycerol, carboxymethylcellulose, and bovine serum albumin solutions into ex vivo porcine skin. The experimental dataset was augmented and analyzed using five conventional machine-learning algorithms as well as a neural network model. Predictor variables included viscosity, stagnation pressure, jet velocity, Reynolds number, and fluid type. Results indicated that increasing viscosity led to reductions in jet diameter, penetration depth, and dispersion across all fluid types, albeit with distinct linear penetration sensitivities. Within the conceptual prediction framework, the multilayer perceptron neural network model demonstrated superior accuracy (R² = 0.85, mean absolute error = 0.13 mm), outperforming other conventional machine learning approaches. By integrating real-tissue microsecond near-infrared visualization with a conceptual, data-driven predictive workflow, this study elucidates the factors underlying variability in penetration scaling across different fluid classes and highlights the challenges of generalizing a single global penetration equation, particularly for non-Newtonian and protein-based formulations.
Brucine-loaded hydrogel microneedles for sustained anti-inflammatory therapy in rheumatoid arthritis: programmable drug release and detachable design.
Qian S, Wan K, Xu J … +7 more , Yao X, Li T, Chen L, Shen L, ShiyunWang, Cai Y, Song X
Drug Deliv Transl Res · 2026 May · PMID 42118496 · Publisher ↗
This study aimed to develop a brucine (Bru) hydrogel-forming microneedle (Bru-HFM) delivery system that could achieve long-term, programmed drug release, through adjusting degree of cross-linking in polyvinyl alcohol (PV...
This study aimed to develop a brucine (Bru) hydrogel-forming microneedle (Bru-HFM) delivery system that could achieve long-term, programmed drug release, through adjusting degree of cross-linking in polyvinyl alcohol (PVA)/carbomer 934P (CP) hydrogel. A one-way orthogonal experiment and a Franz diffusion cell were employed to optimize the preparation process. The resulting Bru-HFM exhibited favorable appearance, mechanical strength, and swelling properties. The drug release performance of the different drug-carrying sites of HFMs was compared. The results illustrated that in vivo drug release rate over 144 h was significantly higher in the needle body-carrying group (95.32%) than in the whole-microneedle (51.85%) and back-lining groups (57.39%). The amount of residue in the back-lining group was obvious, in line with expectations. The burst release rate of 78.81% could meet the high-dose demand during the acute phase of inflammation, whereas continuous release through the cross-linking network over 48-144 h achieved a total release rate of 95.32%. This covered the maintenance phase of chronic inflammation treatment, and the microneedles remained structurally intact at the end of drug release, permitting their detachable. The general pharmacodynamic evaluation results demonstrated that the pathological state of the ankle joints of rats with collagen-induced arthritis was significantly improved in the needle body-carrying group, which also exhibited significantly reduced serum levels of IL-6, IL-17, and TNF-α (all P < 0.05), indicating a significant therapeutic effect on rheumatoid arthritis. This study provides a new strategy and theoretical basis for designing HFMs for programmed drug release and inflammatory disease treatment.
Multiprotein-based nanomedicines with dual CD44/CD133 targeting and GSH-responsive drug release for improving cancer chemotherapy.
Yu LY, Shueng PW, Wang YH … +6 more , Yen YW, Chen KW, Li CR, Chiu HC, Lin YW, Lo CL
Drug Deliv Transl Res · 2026 May · PMID 42115530 · Publisher ↗
Albumin, a highly biocompatible protein, has been utilized in the construction of anti-cancer drugs for the treatment of various cancers. However, albumin-based nanomedicines still face several clinical challenges, inclu...
Albumin, a highly biocompatible protein, has been utilized in the construction of anti-cancer drugs for the treatment of various cancers. However, albumin-based nanomedicines still face several clinical challenges, including low stability in the bloodstream, non-specific targeting ability, and lack of controlled release capability. To address these limitations, we developed a multiprotein-based nanomedicine for targeted chemotherapy of non-small cell lung cancer (NSCLC). This nanomedicine was assembled using a heart-shaped albumin and two Y-shaped anti-CD44 and anti-CD133 antibodies. To enhance stability and improve therapeutic efficacy, the multiproteins were crosslinked using disulfide bond linkers and loaded with paclitaxel and ceramide. This resulted in nanomedicines that exhibited responsiveness to glutathione (GSH) and demonstrated inhibition of tumor cancer cells and cancer stem cells (CSCs). Our experimental results indicated that the inclusion of anti-CD44 and anti-CD133 antibodies enhanced the targeting capability of nanomedicines towards cancer cells and CSCs in an in vitro study and the accumulation in both normoxic regions and hypoxic niches in in vivo tumor xenografts. The multiprotein-based nanomedicines also demonstrated GSH-dependent drug release behavior, induced apoptosis in cancer cells and CSCs, inhibited cell migration, and effectively suppressed NSCLC tumor growth. Overall, our findings presented a novel nanostructure created from differently shaped proteins for application in drug delivery. This multiprotein-based nanomedicines showed promising potential in addressing the limitations of albumin-based nanomedicines and may offer improved therapeutic outcomes for cancer treatment.
Mannose-modified IL-10 mRNA nanoparticle delivery system promotes M2 macrophage polarization and ameliorates early immune dysregulation in sepsis.
Rao Q, Pan B, Peng Z … +3 more , Yu Q, Yu Y, Wang H
Drug Deliv Transl Res · 2026 May · PMID 42113467 · Publisher ↗
Dysregulated immune responses and excessive inflammation are central drivers of early sepsis progression. Interleukin-10 (IL-10) is a key anti-inflammatory cytokine. However, the therapeutic potential and mechanistic bas...
Dysregulated immune responses and excessive inflammation are central drivers of early sepsis progression. Interleukin-10 (IL-10) is a key anti-inflammatory cytokine. However, the therapeutic potential and mechanistic basis of IL-10 mRNA delivery in correcting early immune dysfunction during sepsis remain poorly defined. In this study, we developed a mannose-modified mesoporous silica nanoparticle system (MMP/IL-10 mRNA) to stabilize IL-10 mRNA and enable sustained release for the immunoregulatory treatment of sepsis. The nanoparticles exhibited uniform size, structural stability, efficient mRNA protection, and sustained IL-10 expression. In LPS-stimulated macrophages, MMP/IL-10 mRNA enhanced cell viability, promoted M2 polarization, suppressed pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6, and IL-17A), and restored the IL-10/IL-17A balance. In a cecal ligation and puncture-induced murine sepsis model, MMP/IL-10 mRNA improved 7-day survival, enhanced bacterial clearance, alleviated lung and liver injury, and ameliorated systemic inflammatory imbalance. Mechanistically, treatment reduced TLR4 expression, prevented IκBα degradation, inhibited NF-κB p65 phosphorylation, and upregulated endogenous IL-10 and DEL-1. Importantly, no detectable toxicity or organ damage was observed. These findings demonstrate that MMP/IL-10 mRNA enables efficient, sustained, and safe delivery of IL-10 mRNA, attenuates early hyper-inflammation, and improves immune dysregulation in sepsis, highlighting its potential as a promising immunoregulatory therapeutic strategy.
Intranasal nanoemulsion for targeted medication delivery to the brain: a novel approach to treat psychotic disorder.
Das S, Sarkar M, Bagchi A … +1 more , Bahadur S
Drug Deliv Transl Res · 2026 May · PMID 42113466 · Publisher ↗
The brain is one of the most delicate & protected organs of the human body. The circulation of blood to the brain is secured by the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and cerebrospinal...
The brain is one of the most delicate & protected organs of the human body. The circulation of blood to the brain is secured by the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and cerebrospinal fluid-brain barrier (CBB). These barriers also restrict the distribution of therapeutics to the central nervous system (CNS) for the treatment of any psychotic disorder. Oral & parenteral routes are the main routes for the delivery of anti-psychotics to the brain. Still, associated drawbacks include the stomach's acidic pH, first-pass metabolism, enzymatic degradation, plasma protein binding and finally, the barriers of brain. One of the novel routes for directly targeting the drug to the brain is the intranasal route, which bypasses the BBB. The drug is delivered to the brain via the olfactory & trigeminal nerve regions located in the septum & ceiling of the nasal cavity, reaching the brain more quickly and at higher concentrations than viat the systemic circulation or other tissues. In most cases, nasal doses are 2-10 times less than the oral dose. Nanoemulsions (NE) are bi-phasic dosage forms of two immiscible liquids stabilized by surfactants having a mean droplet size of 100-300 nm. NE is attracting increasing interest in nose-to-brain delivery (N2B) due to its ability to address issues related to drug solubility & drug stability. The smaller droplet size of NE provides a larger surface area, thereby increasing the dissolution rate according to the Noyes-Whitney equation.
Double-coated PLGA nanoparticles with hierarchical surface architecture for CD44-targeted siRNA delivery.
Longobardi G, Shekhter P, Conte C … +2 more , Satchi-Fainaro R, Quaglia F
Drug Deliv Transl Res · 2026 May · PMID 42104082 · Publisher ↗
Efficient delivery of small interfering RNA (siRNA) remains a materials challenge because it requires nanocarriers that stabilize polyanionic cargo, support cellular interactions, and enable cytosolic delivery. Although...
Efficient delivery of small interfering RNA (siRNA) remains a materials challenge because it requires nanocarriers that stabilize polyanionic cargo, support cellular interactions, and enable cytosolic delivery. Although poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are used due to biocompatibility, biodegradability, and regulatory acceptance, siRNA delivery with PLGA requires interfacial engineering to meet these constraints. Here, a modular double-coated PLGA NP platform (dcNPs2.0) is developed and optimized for siRNA complexation, surface functionalization, and scalable manufacturing. The system comprises a PLGA core coated with a polyethyleneimine (PEI) interlayer to mediate siRNA binding, followed by a hyaluronic acid (HA) outer layer, which improves colloidal stability and promotes CD44-mediated uptake. Process optimization, including transition from batch nanoprecipitation to microfluidic fabrication, provides high yield, excellent reproducibility, narrow size distributions, and increased siRNA loading. X-ray photoelectron spectroscopy confirms hierarchical multilayer assembly. The optimized dcNPs2.0 formulation exhibited robust physicochemical stability during storage, in serum-containing media, and following lyophilization with appropriate cryoprotection. Functional evaluation of dcNPs2.0 demonstrated efficient HA-mediated cellular uptake and effective silencing following siRNA delivery in both two-dimensional monolayers and three-dimensional spheroids of MDA-MB-231 cells. Overall, this work establishes a scalable, rationally engineered PLGA nanoplatform that integrates extracellular targeting with intracellular delivery requirements for siRNA therapeutic applications.
Intranasal lipid nanocapsule administration of the new lipophenol quercetin-3-O-DHA-7-O-iPr reduces carbonyl stress and improves behavior in a mouse model of Alzheimer's disease.
Otaegui L, Lehoux J, Begu S … +10 more , Moujellil-Legagneur T, Zussy C, Vitalis M, Mathias M, Beau A, Durand T, Givalois L, Bernoud-Hubac N, Crauste C, Desrumaux C
Drug Deliv Transl Res · 2026 May · PMID 42091792 · Publisher ↗
Oxidative and carbonyl stresses (COS), which damage brain cells through the accumulation of toxic reactive carbonyl species (RCS), are key players in the etiology of Alzheimer's disease (AD). Our group developed lipophen...
Oxidative and carbonyl stresses (COS), which damage brain cells through the accumulation of toxic reactive carbonyl species (RCS), are key players in the etiology of Alzheimer's disease (AD). Our group developed lipophenols, i.e. COS-targeting hybrid molecules combining polyunsaturated fatty acids (PUFAs) and alkyl-(poly)phenols. Among them, quercetin-3-O-docosahexaenoate-7-O-isopropyl (Quercetin-3-O-DHA-7-O-iPr or "Q-iP-DHA") afforded neuroprotection against acrolein-induced toxicity, reduced carbonyl stress, and lowered amyloid-beta secretion in neuroblastoma cells. To evaluate Q-iP-DHA in vivo, it was formulated into lipid nanocapsules (to allow solubilization) then administered intranasally to J20 transgenic mice, a model of AD. This approach was chosen to optimize blood-brain barrier (BBB) penetration. This delivery led to improvements in well-being, organizational skills and spatial memory. In addition, Q-iP-DHA treatment reduced hippocampal amyloid plaque numbers, normalized expression of the Receptor for Advanced Glycation End-products (RAGE), and decreased microglial activation, indicating anti-inflammatory effects. Overall, our preclinical findings suggest that intranasal administration of nanoformulated Q-iP-DHA may represent a promising multitarget therapeutic approach against AD.
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