Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
Assessment of microneedle array insertion into skin using Raman spectroscopic techniques.
Jamaledin R, Zarmpi P, Alambiaga-Caravaca AM … +7 more , Tyagi V, Anjani QK, Larrañeta E, Donnelly RF, Belsey NA, Guy RH, Delgado-Charro MB
Drug Deliv Transl Res · 2026 Jan · PMID 41528720 · Publisher ↗
Microneedle (MN) arrays bypass the skin's stratum corneum barrier to deliver drugs directly into the viable tissue. The skin disposition of three types of MNs-dissolvable, degradable and hydrogel-forming, fabricated usin...
Microneedle (MN) arrays bypass the skin's stratum corneum barrier to deliver drugs directly into the viable tissue. The skin disposition of three types of MNs-dissolvable, degradable and hydrogel-forming, fabricated using different polymers-have been evaluated post-treatment with examples of these MN arrays and then examined by confocal Raman spectroscopy and stimulated Raman scattering (SRS) microscopy. The presence of the polymers was assessed from their characteristic Raman signals. SRS image mosaics were acquired to survey and visualise larger areas of the skin surface. After MN insertion, the skin's spectrum was acquired using confocal Raman spectroscopy at the surface, and at nominal depths of 50 µm, 100 µm, and 150 µm. For dissolvable and degradable MNs, Raman signals from the constituent polymers were detectable in the skin. However, the polymer used to form the hydrogel MNs was not detectable under the experimental conditions used. SRS confirmed that the MN arrays penetrated the skin in a reasonably uniform manner. In summary, polymeric MN insertion into the skin has been visualised using confocal Raman spectroscopy and SRS microscopy. Together, these techniques have the potential to shed light on the spatial and temporal skin disposition of the constituent MN polymers used.
First-in-line 3D-printed intravaginal ring for nonhormonal contraception.
Howard SA, Bhutta MS, Janusziewicz R … +4 more , Trujillo AP, Cohen AL, Doncel GF, Benhabbour SR
Drug Deliv Transl Res · 2026 Jan · PMID 41526592 · Publisher ↗
With nearly half of all pregnancies occurring unintended, effective and acceptable contraceptive options remain a global necessity. Though contraceptives with extended durations of action reduce the need for strict daily...
With nearly half of all pregnancies occurring unintended, effective and acceptable contraceptive options remain a global necessity. Though contraceptives with extended durations of action reduce the need for strict daily adherence, thus enhancing compliance and reliability, only one of these methods - the copper intrauterine device (IUD) - prevents pregnancy without administering exogenous hormones. Herein, we demonstrate co-delivery of two nonhormonal contraceptive agents, lactic acid (LA) and glycerol monolaurate (GML), using a next-generation 3D-printed intravaginal ring (IVR). Through alterations in ring properties and drug loading, a range of LA and GML release rates were achieved in vitro, demonstrating the flexibility of the platform technology. Rings elicited sustained release of LA and GML at target release rates over 30 days or longer. Additionally, these studies explored how drugs with different physiochemical properties interact within the IVR matrix and further elucidated IVR drug loading and release mechanisms.
Self-assemblies from prodrugs composed of antimicrobial peptides: a revolution in local lung cancer treatment, with microbiota as a main actor.
Ladaycia A, Lemaire L, Pailhoriès H … +6 more , Lautram N, Franconi F, Pigeon P, Jaouen G, Passirani C, Lepeltier E
Drug Deliv Transl Res · 2026 Jan · PMID 41501309 · Publisher ↗
Human microbiota is now recognized as a fundamental organ of the body. In its healthy state, it fulfills essential local and systemic functions, whereas dysbiosis disrupts these roles and can contribute to disease. Altho...
Human microbiota is now recognized as a fundamental organ of the body. In its healthy state, it fulfills essential local and systemic functions, whereas dysbiosis disrupts these roles and can contribute to disease. Although numerous studies have examined the relationship between microbiota and cancer, often revealing conflicting mechanisms and outcomes, this work has focused almost exclusively on the gut, leaving the lung microbiota largely unexplored. In this project, a ferrocifen compound was selected as an anticancer agent for lung cancer therapy. We found that lung microbiota actively degraded the ferrocifen. To prevent this degradation, the antibacterial peptide buforin II was synthesized, purified, and characterized. After confirming its antimicrobial activity, it was covalently conjugated to the ferrocifen, yielding an amphiphilic bioconjugate. This prodrug was subsequently formulated into self-assembled structures to enhance ferrocifen solubility and bioavailability. The resulting self-assemblies were evaluated in an orthotopic murine model of lung cancer and administered via nebulization to assess their therapeutic efficacy. A significant reduction in tumor progression and an improved predicted survival in mice were obtained. Together, these findings highlight the capacity of the lung microbiota to interfere with anticancer therapies and underscore the importance of considering this flora when designing treatment strategies for lung cancer.
Engineering access to the brain: nanotechnologies at the interface of delivery, neurology, and immunotherapy.
Merkel OM, Hu SH, Fornaguera C
Drug Deliv Transl Res · 2026 Mar · PMID 41495334 · Publisher ↗
Abstract loading — click title to view on PubMed.
Biomimetic platelet-membrane camouflaged ivermectin nanocrystals for tumor homing and breast cancer management.
Sheir MM, El-Habashy SE, Sheta E … +2 more , Nasra MMA, Abdallah OY
Drug Deliv Transl Res · 2026 Jan · PMID 41495333 · Publisher ↗
Leveraging the intrinsic platelet-cancer cell crosstalk through platelet membrane-coated nanosystems offers a promising avenue for targeted drug delivery, particularly against triple-negative breast cancer, the most aggr...
Leveraging the intrinsic platelet-cancer cell crosstalk through platelet membrane-coated nanosystems offers a promising avenue for targeted drug delivery, particularly against triple-negative breast cancer, the most aggressive highly metastatic breast cancer subtype. In parallel, repurposing the antiparasitic ivermectin (Ivm) for anticancer applications is hindered by poor solubility and high toxicity, restricting its parenteral administration. In this study, ivermectin nanocrystals (Ivm-NC) were first developed to enhance drug solubility and systemic delivery. Afterwards, platelet-membrane was employed for realizing platelet-mimetic-camouflaged PMV/Ivm-NC for active-targeted tumor homing, immune evasion and higher biocompatibility. The innovative PMV/Ivm-NC presented optimum particle-size and zeta-potential, while exhibiting a sustained release pattern. Successful coating and retention of platelet membrane proteins was confirmed by SDS-PAGE profiling and immunocytochemistry for the platelet-membrane-protein P-selectin. In vitro studies for PMV/Ivm-NC demonstrated higher selective-cytotoxicity (IC 2.89 ± 0.38 µg/mL) and anti-migratory potential on MDA-MB-231 cells, and cytocompatibility on normal human fibroblasts vs. uncoated Ivm-NC. In 4T1-tumor-bearing BALB/c mice, PMV-functionalization fostered preferential tumor-homing and reduced off-target distribution, compared to uncoated-NC. In addition, PMV/Ivm-NC secured pronounced tumor-growth inhibition, down-regulation of oncogenic markers (VEGF and cyclin D1), upregulation of pro-apoptotic Bax and caspase-3, and enhanced immune-infiltration of CD4 and CD8 T-cells, suggesting Ivm-induced immunogenic cell death. Histological evaluation confirmed higher tumor-necrosis and lower mitotic-count, as well as a notable lung-antimetastatic activity. Serum biochemistry and histopathology confirmed favorable biocompatibility. Together, our findings highlight PMV/Ivm-NC as a promising biomimetic-camouflaged nanoplatform for harnessing Ivm repurposed anticancer immunotherapy and reducing possible toxicity with selective, active targeting of triple negative breast cancer.
Intraoperative drug delivery to hindbrain tumours via an injectable hydrogel is well tolerated and confers survival benefit against atypical teratoid/rhabdoid xenografts.
Moloney C, McCrorie P, ElSherbeny A … +24 more , Porter H, Bastiancich C, Slika H, Shahani A, Derin E, Velarde E, Miller J, Theodore J, Varshney K, Ruchika FNU, Bayraktutan H, Oz UC, Collier P, Paine SML, Handley P, Dredge K, Wicher G, Grundy RG, Brem H, Forsberg-Nilsson K, Smith SJ, Tyler B, Alexander C, Rahman R
Drug Deliv Transl Res · 2026 Jul · PMID 41484490 · Full text
Intraoperatively applied local drug delivery systems (LDDS) offer a means of overcoming blood-brain barrier (BBB) impermeability. However, there is a paucity of LDDS development for paediatric tumours arising in the post...
Intraoperatively applied local drug delivery systems (LDDS) offer a means of overcoming blood-brain barrier (BBB) impermeability. However, there is a paucity of LDDS development for paediatric tumours arising in the posterior fossa. Here we demonstrate applicability of an LDDS against medulloblastoma group 3 (G3 MB) and atypical teratoid/rhabdoid tumours (AT/RT), neoplasms associated with poor prognoses. A poly(ethyleneglycol)-poly(caprolactone)-poly(ethyleneglycol) (PECE) hydrogel loaded with chemotherapeutics identified as effective against primary G3 MB and AT/RT in vitro, was prepared as an injectable, biodegradable formulation. CHIR99021 (glycogen synthase kinase-3 inhibitor), ribavirin (guanosine analogue) and PG545 (heparanase inhibitor) were chosen based upon an inability to traverse the BBB. The hydrogel alone was well-tolerated, and drug-loaded hydrogel achieved > 1-month therapeutic release. Orthotopic xenograft studies against G3 MB and AT/RT indicated good tolerability to combined CHIR99021 and PG545 or combined CHIR99021 and ribavirin loaded loaded LDDS respectively. Median survival of AT/RT arms receiving XRT alone was comparable to CHIR99021- and ribavirin-loaded LDDS, with long-term survivors observed only in the latter arm, demonstrating a significant survival benefit. LDDS against cerebellar tumours using PECE offers a promising therapeutic alternative and the possibility of circumventing radiation-induced adverse effects for children impacted by these diseases.
Bionic platelet membrane-coated rutin nanoparticles attenuate ulcerative colitis by suppressing platelet-mediated macrophage inflammation.
Zhang R, Mei R, Liang B … +6 more , Zhang X, Zhang T, Luo J, Zhang J, Pan Q, Yan Y
Drug Deliv Transl Res · 2025 Dec · PMID 41454161 · Publisher ↗
Ulcerative colitis (UC) is a chronic, immune-mediated disorder with limited treatment efficacy due to drug resistance. As key immune effectors, Macrophages drive UC pathogenesis: The M1 polarization promoted through P-se...
Ulcerative colitis (UC) is a chronic, immune-mediated disorder with limited treatment efficacy due to drug resistance. As key immune effectors, Macrophages drive UC pathogenesis: The M1 polarization promoted through P-selectin/PSGL-1 binding between platelets and macrophages exacerbates inflammation. Rutin-PEG-PLGA nanoparticles (P@Rut) were engineered by encapsulating rutin in PEG-PLGA cores. Biomimetic platelet membrane nanoparticles (PP@Rut) were synthesized by extracting platelet membranes and coating P@Rut. The blockade of platelet-macrophage interactions by PP@Rut was assessed in vitro and in vivo. The inhibition of macrophage polarization and JNK/STAT1 pathway was evaluated via immunofluorescence (CD86/CD206) and RT-qPCR (IL-1β, TNF-α, TGF-β). Apoptosis was quantified using flow cytometry and TUNEL staining, complemented by Western blot analysis of apoptosis-related proteins(Bcl-xl, Bak, and cleaved-caspase3). Additionally, intestinal barrier integrity was assessed through tight junction protein expression (Occludin, Claudin-1, ZO-1), while therapeutic efficacy was determined via colon length, body weight, disease activity index (DAI) scores, and H&E staining histopathological analysis. PP@Rut significantly shifted macrophage polarization from M1 to M2 through the JNK/STAT1 pathway, suppressed inflammatory response, reduced mucosal epithelial cells apoptosis, and improved intestinal barrier integrity. In DSS-induced mice, PP@Rut demonstrated higher accumulation in inflamed colon versus P@Rut, ameliorating body weight loss, DAI scores, colon shortening, and histopathological injury, including the reduction in inflammatory infiltration and crypt damage. PP@Rut represents a synergistic nanotherapeutic strategy that competitively inhibits platelet-macrophage binding to reprogram polarization, suppress inflammation, and restore barrier function in UC.
Preparation of Tanshinone IIA and glycyrrhetinic acid emulsion and preliminary study on its anti-psoriasis efficacy.
Dong R, Hu D, Qiu R … +1 more , Wang X
Drug Deliv Transl Res · 2026 Jun · PMID 41449306 · Publisher ↗
AIM: The current work highlighted the preparation method of Tanshinone IIA, Glycyrrhetinic acid Emulsion with eutectic (GT-eEmu) and investigated its effectiveness in the internal and external treatment of psoriasis. MAT...
AIM: The current work highlighted the preparation method of Tanshinone IIA, Glycyrrhetinic acid Emulsion with eutectic (GT-eEmu) and investigated its effectiveness in the internal and external treatment of psoriasis. MATERIALS & METHODS: The optimal prescription ratios of the emulsions were screened based on single-factor and orthogonal experiments, in which the appearance, particle size, centrifugal stability, and placement stability of the emulsion were used as indicators. On this basis, the maximum drugs loading was determined and optimized by D-optimal. Then the gloss, consistency, uniformity, spreading, and centrifugal stability of the emulsion gel were used as indicators to screen the best preparation method of the emulsion gel. The gastrointestinal stability of GT-eEmu and the original drug was evaulated by the artificial gastrointestinal fluid test, while the irritation to the the gastrointestinal mucosa was investigated after treatment. In addition, the skin permeability and skin side effects of the preparation were studied. Finally, the therapeutic effects of various preparations on psoriasis in mice were studied based on PASI scores, HE pathological sections and the expression of SOCS1 and STAT3. RESULTS: The best optimized prescription of GT-eEmu was: oil phase 7%, emulsifier 4.5%, and emulsification temperature 60 ℃, where the drug loading of TSN IIA and GA were 0.17 and 0.70 g·L. The best preparation method for GT-eEmu-Gel was to add carbomer 980 with 6% gel matrix to the emulsion prepared by the optimized method, followed by mixing with triethanolamine and adjusting the pH to 6.0-7.0 to prepare a 0.5% carbomer matrix emulsion. The gastrointestinal stability experiment showed that the addition of eutectic ingredients did not cause significant irritation to the gastrointestinal tract, while the good permeability and sustained release of GT-eEmu-Gel were shown by in vitro release assays and the emulsion gel form could further reduce the irritation of eutectic to the skin. Finally, imiquimod-induced psoriasis animal model experiments indicated that GT-eEmu and its gel could reduce the degree of skin lesions and histopathological changes in model mice, and decrease the average expression of SOCS1 and STAT3, which indicated these preparation had therapeutic effects on psoriasis. Additionally, the "internal and external treatment" group had the best effect compared with the oral-only group, while there was a significant difference (P < 0.01) compared with the model group. CONCLUSION: The preparation process of GT-eEmu and GT-eEmu-Gel is stable and quality-controlled, which can improve the oral bioavail ability of both drugs to different degrees and reduce the irritation to the skin. The results showed that they have certain therapeutic effects on psoriasi, which can be safely administered orally and applied externally on the skin. At the same time, compared with the single treatment, the "internal and external combined treatment" method was the most effective, which indicates the concept of "internal and external combined treatment" method has practical significance.
Pharmacokinetic model for drug delivery by Ozurdex.
Bommanahalli Nagaraju K, Dey A, Kompella U … +1 more , Chauhan A
Drug Deliv Transl Res · 2026 Apr · PMID 41437180 · Publisher ↗
Sustained release of drugs by devices such as dexamethasone implant placed in vitreous humor can reduce the frequency of intravitreal injections. The duration over which the device provides therapeutic drug exposure is a...
Sustained release of drugs by devices such as dexamethasone implant placed in vitreous humor can reduce the frequency of intravitreal injections. The duration over which the device provides therapeutic drug exposure is a critical parameter and so models for predicting ocular pharmacokinetics after placing the device in vitreous humor are valuable. This study developed a model using parameters from literature to predict concentrations in aqueous humor, vitreous humor, retina and sclera-choroid after placing Ozurdex in vitreous humor and validated the model using data reported in literature for rabbits and Cynomolgus monkeys. The model is based on ordinary differential equations representing mass balances in vitreous humor, retina, aqueous humor and sclera-choroid. Additionally, a partial differential equation representing mass balance in the lens is included. The model can be simplified to yield explicit expressions for concentration in all tissues. The results are in reasonable agreement with concentrations reported in literature, particularly considering the in vivo data variability and lack of dependence on fitting parameters in the model. The simulation results suggest that the duration of therapeutic concentration in the retina is longer than the drug release duration from the implant because drug diffuses into the lens, creating a depot. The drug depot in the lens eventually releases the drug back into vitreous humor, which increases the total duration over which the concentrations are efficacious. The model can be applied to other sustained release devices placed in vitreous humor or elsewhere in the eye.
Rational design of anticancer multidrug nanosystems and their adaptation for glioblastoma treatment.
Pacheco C, Baltazar F, Costa BM … +1 more , Sarmento B
Drug Deliv Transl Res · 2026 Jul · PMID 41407985 · Publisher ↗
Multidrug nanosystems emerged as an innovation in anticancer therapy, addressing key limitations of conventional mono- and combination therapies, such as poor tumor selectivity, systemic toxicity, low stability and drug...
Multidrug nanosystems emerged as an innovation in anticancer therapy, addressing key limitations of conventional mono- and combination therapies, such as poor tumor selectivity, systemic toxicity, low stability and drug resistance. Following the clinical approval of Vyxeos® in 2018, growing therapeutic interest and advances in nanomedicine have paved the way for a new wave of promising next-generation multidrug nanoparticle candidates. These nanosystems offer the unique ability to co-deliver multiple therapeutic agents, aligning pharmacokinetics, improving tumor targeting, and enabling controlled drug release. By incorporating small molecules, genetic material, peptides, and proteins, multidrug nanosystems can achieve potent anticancer effects that significantly enhance therapeutic outcomes. In glioblastoma context these can play a particularly important role, as treatment is limited by tumor cells resistance, as much as low blood-brain barrier penetration. Here, the design principles underlying anticancer multidrug nanosystems are explored, including concurrent and sequential drug delivery strategies, and highlighting recently proposed advances in drug loading, active targeting, and stimuli-responsive mechanisms. A special focus is placed on how these platforms have been designed to improve or bypass blood-brain barrier penetration, and overcome other glioblastoma resistance mechanism challenges. Besides their therapeutic potential, current challenges, including the need for rational therapeutic combination selection, ensuring biosafety, and balancing potency with cost-effectiveness for clinical translation, are discussed. By summarizing recent advances and addressing the remaining hurdles, this review underscores the transformative potential of multidrug nanosystems in cancer therapy, particularly for the hard-to-treat glioblastoma, and outlines the steps needed to accelerate their path to clinical application.
Topical delivery of Lidocaine using spicules for local anesthesia.
Zhang C, Yang P, Lin X … +6 more , Lai H, Liu Y, Yu S, Liu T, Chen M, Huang Y
Drug Deliv Transl Res · 2025 Dec · PMID 41402578 · Publisher ↗
Topical anesthesia offers a painless alternative to injections but is limited by the low skin permeability of local anesthetics through the stratum corneum, leading to a slow onset. In this study, we introduce a novel sp...
Topical anesthesia offers a painless alternative to injections but is limited by the low skin permeability of local anesthetics through the stratum corneum, leading to a slow onset. In this study, we introduce a novel spicule-assisted topical delivery system using Sponge Haliclona sp. spicules (SHS) combined with Carbomer gel to enhance the transdermal absorption of lidocaine hydrochloride (LH). SHS act as dispersed microneedles, creating numerous microchannels that significantly improve skin permeability. In vitro, SHS increased total skin absorption of LH nearly tenfold (78.45 ± 6.96%) and accelerated drug penetration into deeper skin layers (97.5% in dermis and receptor compartments). In vivo, SHS-LH treatment achieved a maximum anesthetic effect within 10 min, markedly faster and stronger than conventional topical application. A pilot clinical trial confirmed that the SHS-Carbomer gel system halved the onset time of lidocaine and significantly prolonged its anesthetic effect. These findings demonstrate that the SHS-based dispersed microneedle system provides a rapid, safe, and needle-free alternative for local anesthesia, offering a substantial improvement over conventional topical formulations.
Functional and therapeutic effects of Glabrescione B delivery by liposomes on Hedgehog-dependent tumors.
Infante P, Daniele R, Bottero M … +19 more , Longo M, Bufalieri F, Lospinoso Severini L, Pesce C, Fragassi A, Gabbia D, Navacci S, Basili I, Adabbo G, Cammarone S, Cianfoni G, Ghirga F, Mori M, De Martin S, Mancuso M, Caliceti P, Pazzaglia S, Salmaso S, Di Marcotullio L
Drug Deliv Transl Res · 2026 Jul · PMID 41402577 · Full text
Aberrant Hedgehog (HH) signaling pathway is responsible of tumorigenesis of medulloblastoma (MB) and basal cell carcinoma (BCC), two aggressive malignancies with limited therapeutic options. Targeting Gli1, the final and...
Aberrant Hedgehog (HH) signaling pathway is responsible of tumorigenesis of medulloblastoma (MB) and basal cell carcinoma (BCC), two aggressive malignancies with limited therapeutic options. Targeting Gli1, the final and powerful effector of HH signaling, emerged as a valuable strategy for the treatment of HH-dependent tumors. Among Gli1 inhibitors, Glabrescione B (GlaB), is a small molecule that directly inhibits Gli1/DNA interaction, which showed promising pre-clinical results. However, poor solubility limits its clinical translation. To overcome this issue, here we develop a liposomal formulation of GlaB (Lipo/GlaB) with optimized composition to enhance drug loading, controlled release, storage stability and pharmacokinetic performance. Among various formulations, liposomes composed of EPC and cholesterol (95:5 mol/mol%) achieves high GlaB loading efficiency and stability upon lyophilization. Lipo/GlaB inhibits Gli1 transcriptional activity more potently than free GlaB and significantly reduces the expression of HH target genes. Notably, Lipo/GlaB remarkably reduces the tumor growth in HH-driven MB and BCC in in vitro and in vivo models, correlating with decreased HH signaling. Further, pharmacokinetic studies in mice revealed improved plasma disposition, higher AUC, and slower elimination for Lipo/GlaB compared to the free drug. These findings support the therapeutic value of Lipo/GlaB as a selective and potent strategy for targeting HH-dependent cancers, offering improved biopharmaceutical properties and in vivo efficacy compared to non-formulated GlaB.
Adenosine and guanosine-based oligonucleotides-loaded PLGA nanoparticles attenuates progression of surgically induced osteoarthritis.
Kim Y, Han J, Park JY … +1 more , Han S
Drug Deliv Transl Res · 2025 Dec · PMID 41398520 · Publisher ↗
Osteoarthritis (OA) is a chronic degenerative joint disease that lacks effective therapies to halt its progression. While endogenous purinergic signaling-particularly via adenosine-shows promise for reducing inflammation...
Osteoarthritis (OA) is a chronic degenerative joint disease that lacks effective therapies to halt its progression. While endogenous purinergic signaling-particularly via adenosine-shows promise for reducing inflammation, it is limited by short half-life and off-target effects. To address these limitations, we developed an optimal anti-inflammatory adenosine-guanosine-based oligonucleotide encapsulated in poly(lactic-co-glycolic) acid (PLGA)-based nanoparticles (NanoOligo) to enhance in vivo stability and investigated its impact on surgically induced OA models and the underlying mechanisms responsible for its anabolic effects. A large oligonucleotide library (482 unique 10- to 20-mer sequences) was screened in RAW264.7 macrophages under LPS-induced inflammation to identify the most potent candidate, which was then encapsulated into PLGA nanoparticles using a microfluidic system. NanoOligo significantly protected against cartilage degeneration and alleviated pain behaviors in the rat ACLT + pMx model following intra-articular administration. In IL-1β-treated chondrocytes, it markedly suppressed inflammatory cytokines (TNFα, IL-6) and catabolic proteases (MMP-3, MMP-13, ADAMTS5). Mechanistically, NanoOligo's anti-catabolic effects were dependent on A1R and A2AR, leading to activation of the PKA-CREB axis and suppression of p38 MAPK signaling, which in turn reduced oxidative stress and cellular senescence via upregulation of the Sirt1-Nrf2-HO-1 antioxidant pathway. Collectively, these findings support joint-localized purinergic modulation as a potential therapeutic target for OA treatment, aligning structural protection with improvements in pain-related behaviors.
Voriconazole nanosuspension-loaded ocular bilayer dissolving microneedle patch for the management of fungal keratitis.
Gowda BHJ, Pandya AK, Gade S … +7 more , Duncan R, Paredes AJ, Ahmed MG, Tian Y, Donnelly RF, Thakur RRS, Vora LK
Drug Deliv Transl Res · 2026 Apr · PMID 41364403 · Full text
Fungal keratitis (FK), caused by fungi like Aspergillus, Fusarium, and Candida, accounts for 20-60% of microbial keratitis cases and over 1 million visual impairments annually. Voriconazole (VOR) is effective against FK,...
Fungal keratitis (FK), caused by fungi like Aspergillus, Fusarium, and Candida, accounts for 20-60% of microbial keratitis cases and over 1 million visual impairments annually. Voriconazole (VOR) is effective against FK, but its eye drop formulations suffer from poor bioavailability, while intrastromal injections are invasive and carry risks. This study aimed to address these challenges by formulating a VOR nanosuspension (NS) and fabricating an ocular bilayer dissolving microneedle array patch (dMAP) incorporating the VOR NS for localized drug delivery to the cornea. The VOR NS was prepared using an aqueous media milling method with polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) as stabilizer and cryoprotectant, resulting in stable nanosized particles with a mean size of 270.11 ± 5.82 nm and a PDI of 0.217 ± 0.019. The formulation demonstrated a 1.71-fold increase in saturation solubility and a high drug content (72.5%). Both VOR NS and free VOR were incorporated into the MAP tips using a two-layer casting method. The VOR NS-loaded bilayer dMAP exhibited higher drug content (118.84 ± 20.67 µg) compared to the free VOR-loaded bilayer dMAP (83.08 ± 2.69 µg). Additionally, they demonstrated superior mechanical strength, greater insertion depth (~ 390 μm), and faster tip dissolution in excised porcine corneal tissue (~ 5 min) compared to the free VOR-loaded bilayer dMAP. Ex vivo studies showed that the VOR NS-loaded bilayer dMAP deposited 47.38 ± 8.08 µg of drug into the porcine cornea, 2.31 times more than the free VOR-loaded bilayer dMAP (20.43 ± 6.11 µg), closely approximating the clinical dose used in VOR intrastromal injections (50 µg/0.1 mL). Furthermore, the disc diffusion assay revealed that VOR NS and VOR NS-loaded bilayer dMAP had greater antifungal activity against Candida albicans and Aspergillus fumigatus compared to free VOR and free VOR-loaded bilayer dMAP. Biocompatibility was confirmed through a human corneal epithelial cell viability assay, and ocular irritation potential was evaluated using the HET-CAM assay, revealing a safe and non-irritant profile. Thus, this innovative NS-MAP hybrid system offers efficient drug delivery with minimal invasiveness and could potentially improve therapeutic outcomes in the management of FK.
Formulation and characterization of exenatide-loaded PLGA microspheres prepared by coacervation.
White C, Schwendeman SP
Drug Deliv Transl Res · 2025 Dec · PMID 41364402 · Publisher ↗
Bydureon is a once-weekly injection of poly(lactide-co-glycolide) (PLGA) microspheres containing exenatide acetate, a synthetic analog of the GLP-1 receptor agonist exendin-4. These microspheres are formulated by coacerv...
Bydureon is a once-weekly injection of poly(lactide-co-glycolide) (PLGA) microspheres containing exenatide acetate, a synthetic analog of the GLP-1 receptor agonist exendin-4. These microspheres are formulated by coacervation (i.e., phase separation), using a single-emulsion method. There remains a knowledge gap between how formulation variables affect product attributes and performance. We aimed to bridge this gap by evaluating the effect of formulation variables on encapsulating exenatide in PLGA microspheres at similar compositions to Bydureon. We first screened process variables without peptide to establish stability windows during coacervation, i.e., conditions that produced high yields of well-formed microspheres. We introduced exenatide during coacervation as a function of PLGA concentration, DCM (dichloromethane): water and DCM: Si oil (polydimethylsiloxane) volume ratios, hold time between Si oil addition and heptane bath immersion, and other manufacturing conditions. We evaluated the formulation yield, residual solvent content, encapsulation efficiency, and 24-h release. A PLGA concentration of 6% w/w was selected because of its wide range of stable formulations with varying DCM: Si oil phase volume ratios. The hold time between Si oil addition and heptane immersion was set at 1 min, although microspheres were stable between a range of 10 s to 2 min. The resultant formulations displayed elevated yields of > 50%, and a low in-vitro 24-h burst release of 2-6%. These formulations exhibited continuous release profiles of predominantly parent and glycolic acid acylated peptide for over 56 days in vitro, as expected by the commercial product. The framework of conditions and their effects on the formulations was established for loading exenatide in PLGA microspheres with desirable release characteristics. These results are useful for both microencapsulation of generic and new peptides in PLGA microspheres by coacervation.
Oromucosal films for peptide delivery: formulation strategies using permeation enhancers and polymers.
Karki S, Malhotra S, Ijaz M … +3 more , O'Cearbhaill ED, Nielsen LH, Brayden DJ
Drug Deliv Transl Res · 2026 Jul · PMID 41354997 · Publisher ↗
Buccal and sublingual mucosae offer highly vascularized, patient-acceptable routes for systemic peptide delivery, providing a promising alternative to peptide injections and conventional oral peptide dosage forms that su...
Buccal and sublingual mucosae offer highly vascularized, patient-acceptable routes for systemic peptide delivery, providing a promising alternative to peptide injections and conventional oral peptide dosage forms that suffer from enzymatic degradation, limited permeability, and hepatic first-pass metabolism. Despite these advantages, achieving consistent peptide bioavailability from oromucosal dosage forms remain challenging due to salivary washout, enzymatic instability, and the compact, lipid-rich epithelial structure. This review provides a comprehensive overview of formulation strategies developed to overcome these barriers, with an emphasis on the use of permeation enhancers (PEs), mucoadhesive polymers, and multilayer film architectures. Advances in nanoparticle-integrated films are highlighted for their potential to improve peptide stability and mucosal permeation. The review concludes by addressing patient compliance, translational potential, and regulatory perspectives that shape the clinical advancement of peptide-loaded oromucosal films.
Nanocarrier-based intranasal drug delivery for enhanced neurological disorders treatment.
Morim E, Sarmento B, Pacheco C
Drug Deliv Transl Res · 2026 Mar · PMID 41345369 · Publisher ↗
The blood-brain barrier (BBB) represents a major obstacle in the treatment of neurological disorders. While it plays a crucial role in protecting the central nervous system (CNS) from harmful xenobiotics, it also limits...
The blood-brain barrier (BBB) represents a major obstacle in the treatment of neurological disorders. While it plays a crucial role in protecting the central nervous system (CNS) from harmful xenobiotics, it also limits the entry of drugs already in systemic circulation. Intranasal drug delivery has emerged as an interesting, non-invasive strategy to bypass the BBB by exploiting the anatomical connections provided by the olfactory and trigeminal nerves, allowing direct transport from the nasal cavity to the brain. Nevertheless, drugs administered via this route face several challenges, including enzymatic degradation, mucociliary clearance and limited residence time on the nasal mucosa. This review examines the underlying mechanisms of nose-to-brain drug transport and details how recent advances in nanocarrier-based delivery systems, including lipid-based, polymeric-based, protein-based, and inorganic nanoparticles, can be engineered to enhance drug delivery to the brain. Recent preclinical advances demonstrate improved brain targeting, protection from degradation, and controlled release profiles. Finally, we summarize the current clinical progress and provide our perspective on the steps needed for successful clinical translation, emphasizing the importance of optimizing nanosystem performance across both the nasal cavity and brain compartments.
Precision engineering of anti-atherosclerotic herbal nanomedicine: from machine learning-aided active components screening to optimized metal-phenolic network codelivery.
Chen Y, Lu M, Zhang L … +9 more , Chang E, Zhu Q, Xu Q, Gao Z, Pan D, Shen C, Liu Q, Zuo Z, Jiang C
Drug Deliv Transl Res · 2025 Dec · PMID 41345368 · Publisher ↗
Atherosclerosis (AS), a chronic inflammatory disease linked to oxidative stress and lipid imbalance, remains a major cardiovascular threat. Traditional herbs Salvia miltiorrhiza and Carthamus tinctorius exhibit multi-tar...
Atherosclerosis (AS), a chronic inflammatory disease linked to oxidative stress and lipid imbalance, remains a major cardiovascular threat. Traditional herbs Salvia miltiorrhiza and Carthamus tinctorius exhibit multi-target anti-AS potential, yet their compositional complexity limits clinical translation. This study aimed to systematically identify core anti-AS components from these herbs and enhance their anti-AS efficacy via machine learning-aided screening and nanotechnology-driven codelivery. We initially pioneered a machine learning-aided hybrid strategy integrating network pharmacology and quantitative activity relationship (QSAR) modeling to identify four core anti-AS polyphenols (i.e., salvianic acid A, salvianolic acid B, protocatechuic acid, and hydroxysafflor yellow A). Subsequently, a quaternary metal-phenolic network (SSPH-MPN) was engineered for plaque-targeted codelivery, optimized via the median-effect principle for achieving a synergistic effect based on ROS scavenging efficacy. The optimized SSPH-MPN was characterized by a series of studies, including molecular dynamics simulations, UV, DLS, TEM, FTIR, XPS, and ICP-MS. The anti-AS effect of the optimized SSPH-MPN was evaluated by monitoring oxidative status (ROS levels, antioxidant enzymes SOD, GSH-Px, MDA, T-AOC), inflammatory markers (IL-1β, IL-6, TNF-α), lipid metabolism (DiI-oxLDL uptake, cholesterol efflux, blood lipid levels, lipid accumulation), and plaque areas. The results demonstrated that the optimized SSPH-MPN showed great efficiency in inhibiting lipid uptake and accumulation, and mediating cholesterol efflux in RAW 264.7 cells, and exhibited improved lipid metabolism, attenuated oxidative stress and inflammation, thus acquired diminished plaque area in apoE mice. Furthermore, biocompatibility was assessed through hemolysis, cytotoxicity assays, and in vivo safety studies, confirming its suitability as a safe therapeutic agent. In conclusion, this work not only identified four anti-AS polyphenols from traditional herbs but also established an MPN-based co-delivery system for synergistic anti-AS therapy, providing a comprehensive paradigm from drug discovery to formulation development.
Smart nanocarriers in triple-negative breast cancer: recent advances in targeting and translational application.
Mishra A, Gole VL, Ojha S
Drug Deliv Transl Res · 2025 Dec · PMID 41343014 · Publisher ↗
Breast cancer remains one of the most prevalent causes of cancer-related mortality worldwide. Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that has a poor prognosis and limited therap...
Breast cancer remains one of the most prevalent causes of cancer-related mortality worldwide. Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that has a poor prognosis and limited therapeutic options. Smart nanocarriers have been developed through significant advancements in nanotechnology over the past few years. To increase therapeutic effectiveness while reducing systemic toxicity, recent developments in nanotechnology have led to the creation of smart nanocarriers-nanosystems designed to carry drugs in a targeted, stimulus-responsive manner. Liposomes, dendrimers, micelles, carbon nanotubes, and polymeric nanoparticles are among the most common types of smart nanocarriers discussed in this study. Their design principles and functional features characterize the many forms of smart nanocarriers. Targeting techniques specific to breast cancer are highlighted, with a particular focus on active targeting via ligands and tumor microenvironment-responsive systems applicable to TNBC. By examining the integration of biodegradable materials, green synthesis methods, and alignment with the global Sustainable Development Goals (SDGs), the study also underscores the crucial role of sustainability in nanomedicine. Significant advancements have been made, but several biological, regulatory, and therapeutic issues still hinder the practical application of nanomedicine in treating TNBC. This review highlights key translational roadblocks and proposes strategic solutions to bridge the gap between the bench and the bedside.
Novel crystalline solid dispersions to improve the oral bioavailability and anti-liver cancer effect of Sorafenib.
Zhang Y, Wang Y, Gong B … +3 more , Liu W, Wang J, Hu C
Drug Deliv Transl Res · 2025 Dec · PMID 41335364 · Publisher ↗
This study investigates the interrelationships among drug loading, steric hindrance (S), defined as the spatial constraints imposed by the crystallized polymer network that physically restrict drug crystal growth, effect...
This study investigates the interrelationships among drug loading, steric hindrance (S), defined as the spatial constraints imposed by the crystallized polymer network that physically restrict drug crystal growth, effective glass transition temperature (T), and drug particle size in crystalline solid dispersion (CSD) systems. Furthermore, we examine how CSD formulations enhance dissolution rates, oral bioavailability, and anti-liver cancer efficacy through comprehensive in vitro and in vivo studies. SOR-P188-CSD with different drug loadings were synthesized via spray drying, utilizing Sorafenib (SOR) as the model drug and poloxamer 188 (P188) as the carrier. The association between S/T, drug particle size, and dissolution behavior of CSDs was investigated by probing the crystalline domain (particle size), crystallization kinetics, and interaction dynamics within the CSD matrices. Notably, the particle size of SOR within SOR-P188-CSD exhibited a significant reduction compared to the pure drug. Analysis of crystallization kinetics unveiled a two-step crystallization mechanism for SOR-P188-CSD, where P188 crystallization preceded that of SOR. Intriguingly, an intermolecular interaction between SOR and P188 was observed, exerting an inhibitory effect on the crystallization kinetics of both components. This inhibitory effect escalated concomitantly with increasing drug loading. Within the SOR-P188-CSD system, P188 within formulations featuring low drug loading orchestrated a reduction in drug particle size by modulating the transverse and longitudinal growth rates of SOR, with S serving as the primary influencing factor. Conversely, in formulations with high drug loading, T of CSD interacted with temperature to regulate crystal nucleation and growth rates, thereby reducing drug particle size, with T emerging as the principal influencing factor. Subsequent in vitro and in vivo dissolution studies demonstrated a marked enhancement in the dissolution rate and bioavailability of drugs encapsulated within SOR-P188-CSD formulations compared to the active pharmaceutical ingredient (API). In the nude mouse liver cancer xenograft model, SOR-P188-CSD can significantly inhibit tumor growth by suppressing the expression of angiogenesis related factors (CD31, CD34, VEGF), tumor proliferation related factors (Ki67), and iron death related protein (GPX4). Collectively, our findings underscore the pivotal role of S/T in modulating drug particle size within CSD matrices through distinct mechanisms. Furthermore, our study underscores the potential of P188-mediated CSD formulations in augmenting the dissolution rate and bioavailability of poorly soluble drugs by minimizing drug particle size and sustaining drug supersaturation, thereby enhancing the efficacy of sorafenib in treating liver cancer.
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