Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
A design of experiments study of nasal spray deposition in the alberta idealized nasal inlet.
Felding MS, Cubbin C, Moser C … +2 more , Ajalloueian F, Nielsen LH
Drug Deliv Transl Res · 2026 May · PMID 42091791 · Publisher ↗
Intranasal administration of drugs possesses numerous advantages such as easy and direct application, rapid onset of action and reduced risk of systemic adverse effects. The nasal cavity consists of several regions and e...
Intranasal administration of drugs possesses numerous advantages such as easy and direct application, rapid onset of action and reduced risk of systemic adverse effects. The nasal cavity consists of several regions and especially the respiratory region, known as the turbinates, is considered favorable for drug uptake. Current Food and Drug Administration (FDA) guidelines for in vitro testing of nasal spray formulations recommend characterization of emitted dose, plume geometry, spray pattern, and particle size distribution. However, recommendations or guidelines for assessing regional deposition within the nasal cavity remain lacking. In this study, we used the Alberta Idealized Nasal Inlet for in vitro testing and a design of experiments (DoE) approach to test the regional deposition of a commercially available nasal spray Otrivin. We show that three main parameters (airflow, angle of administration and temperature) play vital roles in the deposition pattern. Furthermore, we uncovered significant effects of administration angle and temperature, as well as combined interactions between airflow and angle, and temperature and airflow. Our results demonstrate the need for introducing a physiologically relevant temperature when conducting in vitro studies, and that combined interactions are vital to investigate and understand for assessing regional deposition of nasal spray formulations in vitro.
Transdermal ropivacaine delivery via hydrogel-forming microneedles: A pain-free alternative for local anaesthesia.
Miatmoko A, Anjani QK, Octavia RT … +7 more , Porfiryeva N, Annuryanti F, Kim GY, Heo JY, Yoon G, Choi A, Donnelly RF
Drug Deliv Transl Res · 2026 May · PMID 42089928 · Publisher ↗
Surgical procedures in critical care settings are often associated with prolonged postoperative pain, which remains a significant clinical challenge. Conventional analgesic strategies typically rely on injection-based de...
Surgical procedures in critical care settings are often associated with prolonged postoperative pain, which remains a significant clinical challenge. Conventional analgesic strategies typically rely on injection-based delivery, which is invasive, requires trained personnel, and carries risks such as infection and tissue damage. To address these limitations, this study developed a minimally invasive transdermal delivery system for the local anaesthetic ropivacaine (ROP) using hydrogel-forming microneedles (HFMNs) combined with drug reservoir tablets. Two HFMN formulations were prepared using Gantrez S-97 (MN1) and PVA-PVP (MN2), each paired with reservoirs fabricated by direct compression (DCT) or lyophilisation (LYO). Insertion capability study demonstrated that MN2 exhibited superior skin penetration compared with MN1. In vitro permeation studies showed that MN2-DCT achieved the highest transdermal delivery of ROP (> 12 mg across dermatomed porcine skin). However, when both permeated and deposited drug (within skin and HFMNs) were considered, LYO reservoirs paired with either MN1 or MN2 resulted in higher total drug delivery over 24 h. This is attributed to the porous structure of LYO tablets, which enhances fluid uptake and rapid dissolution. The retained drug within the skin and HFMN matrix may serve as a depot for sustained release. In vivo evaluation in a postoperative pain mouse model demonstrated that MN2-LYO provided rapid and sustained analgesia, achieving > 50% maximum possible effect (%MPE) within 1 h and maintaining efficacy for up to 72 h, whereas MN1-LYO showed limited analgesic response. Furthermore, both MN1-LYO and MN2-LYO significantly reduced inflammatory cytokines (IL-6 and TNF-α), with the greatest reduction observed for MN2-LYO (~ 50% decrease compared with negative control and subcutaneous ROP groups). Overall, these findings highlight the potential of HFMN-based delivery systems combined with LYO reservoirs as a minimally invasive, patient-friendly alternative to injectable anaesthetics for prolonged postoperative pain management.
Repurposing insulin for Alzheimer's disease treatment: intranasal delivery of a thermoresponsive nanocarrier-based insulin formulation to the brain.
Khan TTS, Wong CYJ, Sheikh Z … +13 more , Fathi A, Maleknia S, Oveissi F, Abrams T, Knox W, van der Hoven J, Antonito A, Murray M, Svolos M, Suman J, Tietz O, Ong HX, Traini D
Drug Deliv Transl Res · 2026 May · PMID 42086977 · Publisher ↗
The Intranasal route provides an effective pathway for insulin delivery to the brain compared to oral/subcutaneous routes as it provides direct access to the brain, bypassing the restrictive blood-brain barrier (BBB), wh...
The Intranasal route provides an effective pathway for insulin delivery to the brain compared to oral/subcutaneous routes as it provides direct access to the brain, bypassing the restrictive blood-brain barrier (BBB), while minimizing systemic exposure. The present study investigated the potential of a thermoresponsive polymer, PNPHO, as a nanocarrier for brain-targeted insulin delivery through the intranasal route, with the aim of repurposing insulin for Alzheimer's disease treatment. Insulin-loaded nanoparticles (NP) were formulated using an advanced crossflow mixing technology with lower (F1) and higher (F2) PNPHO concentrations and characterised in vitro for size, zeta potential, encapsulation efficiencies, stability, drug deposition, and transport and in vivo for biodistribution. Both F1 and F2 NP demonstrated particle sizes ranging from 35.9 to 49.8 nm with low polydispersity index (< 0.3), negative surface charges, high encapsulation efficiencies (> 99%), and conserved structural integrity post 4 weeks of stability study. NP demonstrated significantly greater in vitro nasal deposition compared to insulin alone. Notably, the PNPHO nanocarrier protected insulin from enzymatic degradation, overcoming a key barrier associated with protein/peptide delivery. In vitro drug transport studies showed an initial delay in NP transport across nasal cells due to PNPHO-mucoadhesive properties, followed by increased transport. Significantly enhanced time-dependent NP transport across the BBB cells compared to insulin alone (p < 0.0001) confirmed NP's ability to cross the BBB. In vivo, NP demonstrated prolonged nasal retention and higher brain: serum ratio in mice, suggesting sustained drug release and improved brain delivery compared to insulin alone. Collectively, the study highlight the potential of PNPHO as a promising nanocarrier for achieving targeted and efficient intranasal delivery of insulin to the brain.
Engineered ATP-loaded extracellular vesicles: a dual-functional strategy for improving myocardial infarction therapy.
Ansari FJ, Behroozi J, Chamanara M … +9 more , Shahrezaee M, Shakerimoghaddam A, Mousavi SH, Amanzadeh A, Shokrgozar MA, Tafti HA, Ghorbani M, Greening DW, Heidari R
Drug Deliv Transl Res · 2026 May · PMID 42086976 · Publisher ↗
Myocardial infarction (MI) represents a major component of cardiovascular disease, primarily due to severe energy depletion in ischemic tissue. Extracellular vesicles (EVs) have recently emerged as promising cell-free na...
Myocardial infarction (MI) represents a major component of cardiovascular disease, primarily due to severe energy depletion in ischemic tissue. Extracellular vesicles (EVs) have recently emerged as promising cell-free nanocarriers capable of targeted delivery and intercellular communication. Leveraging these advantages, engineered EVs were investigated in this study as a direct ATP-delivery platform to cardiomyocytes. EVs were functionalized with an anti-myosin antibody to form targeted extracellular vesicles (T-EVs) and subsequently loaded with ATP, generating T-ATP-EVs for selective energy transfer to damaged myocardium. We study viability and apoptosis of ischemia cells by alamar Blue and flowcytometry (annexin-PI) under hypoxic condition in vitro also we use cardiac function, infarct size, and the expression of troponin and α-actin four weeks after MI on MI rat model in vivo for assessment cardiac repair. The results indicate that, compared with no treatment, the use of T-ATP-EVs enhances the viability of hypoxic cells by 46% and reduces apoptosis by 40%. In the animal study, T-ATP-EVs group increase 27% left ventricular ejection fraction (LVEF) also infarct size decrese 28% compared with control group. Additionally, the expression levels of troponin and α-actin increased approximately two-fold when we use T-ATP-EVs in vivo. In this study, T-ATP-EVs were investigated as a strategy to deliver ATP directly to cardiomyocytes and heart tissue . The system described here enhances cardiomyocyte survival and targeting damaged heart tissue which making a significant advancement in the treatment of MI.
Dual role of ascorbyl Palmitate as coagel and adjuvant in experimental antivenom development.
Maslovski FM, Brignone SG, Barrientos B … +10 more , Hernández DR, Alonso MDR, Lopez GL, Ojeda GA, Peyrano F, González AM, Palma SD, Leiva LC, Belkys M, Fusco LS
Drug Deliv Transl Res · 2026 May · PMID 42084804 · Publisher ↗
An ideal vaccine adjuvant should be biocompatible, enable antigen storage and controlled release, and effectively stimulate the immune system. In this study, we evaluated the dual functionality of ascorbyl palmitate (ASC...
An ideal vaccine adjuvant should be biocompatible, enable antigen storage and controlled release, and effectively stimulate the immune system. In this study, we evaluated the dual functionality of ascorbyl palmitate (ASC16): as an adjuvant additive in its dispersed state (120 µM), and as a coagel formed at low temperatures and high ASC16 concentrations (Coa-ASC16), for use in the antivenom development. Coa-ASC16 was prepared by mixing ASC16 with polyethylene glycol 400 (PEG400) and solubilising the mixture at 64 °C for 2 min; subsequently, the formulation was allowed to cool to 40 °C and whole Crotalus durissus terrificus venom, which naturally contains a complex mixture of proteins, was incorporated for 10 s, including major toxins such as crotoxin, serine proteinases, L-amino acid oxidase, and phosphodiesterases. To produce experimental antivenom, mice were immunized with Coa-ASC16 or Freund's adjuvant, with or without the addition of dispersed ASC16. The physicochemical analyses showed that the Coa-ASC16 exhibited a semi-crystalline, viscoelastic structure capable of effectively encapsulating and releasing proteins. The addition of dispersed ASC16 enhanced the immune response induced by both adjuvants (Freund's and Coa-ASC16), yielding up to a 1.2-fold increase in venom-specific IgG titres and an approximately 2.7-fold increase in IgG antibody avidity. ASC16-based formulations were associated with reduced local adverse reactions compared with Freund's adjuvant-based formulations. In conclusion, we propose an alternative ASC16-based formulation obtained at low temperatures that preserves key physicochemical properties and shows minimal impact at the inoculation site. Moreover, the incorporation of dispersed ASC16 as an additive enhances the humoral immune response. Taken together, our results obtained in a murine model position ASC16 as a promising adjuvant, demonstrating reduced local reactogenicity compared with Freund's adjuvant.
Tabletting of single-screw hot melt extruded itraconazole: HPMC-AS amorphous solid dispersion by 3D printing and direct compression.
Milliken RL, Quinten T, Andersen SK … +1 more , Lamprou DA
Drug Deliv Transl Res · 2026 May · PMID 42081178 · Publisher ↗
This study investigated the development of high drug loading amorphous solid dispersions (ASDs) of itraconazole (ITZ) using single screw hot melt extrusion (HME) for fused deposition modelling (FDM) 3D printing (3DP). IT...
This study investigated the development of high drug loading amorphous solid dispersions (ASDs) of itraconazole (ITZ) using single screw hot melt extrusion (HME) for fused deposition modelling (FDM) 3D printing (3DP). ITZ ASDs containing 20-22% w/w ITZ were prepared with Hydroxypropyl methylcellulose acetate succinate, medium grade, medium particle (HPMCAS-MMP) and processed into filaments for 3DP, while a conventional direct compression ASD was produced as a benchmark to assess the influence of manufacturing method on drug release. While both dosage forms were based on the same ASD system, the final tablet compositions differed due to the requirements of each manufacturing method. Solid-state characterisation using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) confirmed the amorphous nature of the formulations. Dissolution studies were conducted in phosphate buffer saline (PBS, pH 7.4). The direct compressed ASD tablets showed rapid drug release (~ 63% in 30 min) while much slower release was observed for the 3D printed tablets. At 30 min F1 (10% triethyl citrate (TEC)) released only 3% and F2 (12.5% TEC) released 6%. This behaviour may be attributed to the printed tablet's dense structure, buoyancy, and formation of a viscous hydrogel barrier at the surface. This study shows that single screw HME can be used to produce ITZ ASDs for both 3DP and conventional tabletting, while also demonstrating that the dense microstructure of 3D printed tablets limits their ability to achieve an immediate release profile. Further optimisation of formulation and tablet design, such as infill will be needed to improve release performance. These findings provide a basis for future formulation and design strategies to enhance the performance of 3D printed dosage forms.
Cellulose and its potential applications in skin biology; a comprehensive review.
Hameed A, Haider A, Wahedi HM
Drug Deliv Transl Res · 2026 May · PMID 42081177 · Publisher ↗
Cellulose is the most abundant natural biopolymer obtained from plants, animals, and microbes. Cellulose is porous, biocompatible, biodegradable, noncytotoxic, and can retain water for a longer period. Therefore, cellulo...
Cellulose is the most abundant natural biopolymer obtained from plants, animals, and microbes. Cellulose is porous, biocompatible, biodegradable, noncytotoxic, and can retain water for a longer period. Therefore, cellulose has various applications in the medical, cosmetic, paper, and food industries. The current review summarizes the recent progress related to the application of cellulose in skin biology. Cellulose is preferable for skin biology applications due to its porosity, and hygroscopic nature that enables it to mimic the extracellular matrix (ECM) of native skin. Cellulose can be modified by combining with other biopolymers to make a functional cellulose composite. Researchers have developed various cellulose composites that are successfully used as wound dressing agents, scaffolds for skin tissue engineering, and vehicles for drug delivery like anticancer or other hydrophobic drugs. Cellulose-based facial masks act as a carrier for active agents like anti-aging, anti-wrinkle, and anti-acne substances. Cellulose can also be used as a stabilizer in the preparation of emulsion-based creams and other cosmetic products. It is concluded that cellulose is a suitable biopolymer in the global marketplace for skin applications, but further advancements should be made to maximize its clinical use.
Exploitation of cholesterol-dependent cytolysins for targeted biosensing and therapeutic systems.
Abanum HO, Watt E, Ho EA
Drug Deliv Transl Res · 2026 May · PMID 42071090 · Publisher ↗
Cholesterol-dependent cytolysins (CDCs) represent a unique and structurally conserved family of pore-forming toxins secreted by Gram-positive bacterial pathogens. These exotoxins significantly contribute to the virulence...
Cholesterol-dependent cytolysins (CDCs) represent a unique and structurally conserved family of pore-forming toxins secreted by Gram-positive bacterial pathogens. These exotoxins significantly contribute to the virulence and pathogenicity of many CDC-expressing organisms. CDCs selectively recognize and bind cholesterol-rich membranes in host cells and undergo subsequent conformational changes leading to pore formation. Beyond their role as virulence factors, their unique membrane-targeting and pore-forming mechanisms have enabled promising avenues in precision biosensing and targeted therapeutic delivery. Recent advances in nanotechnology and biotechnology have enabled diverse and pivotal biomedical applications of CDCs, which encompass their exploitation as potential bacterial vaccine candidates, ligands for targeted drug delivery, biosensors for pathogen detection, and CDC-responsive nanocarriers for targeted therapeutic delivery. This review explores these emerging roles while highlighting critical factors for the design and evaluation of CDC-responsive platforms, as well as strategies for characterizing their interactions with biological systems. While several preclinical models have demonstrated promising in vitro and in vivo data, the clinical translation of CDC-associated therapies remains hindered by challenges which affect their widespread biomedical application. Understanding the biological mechanisms and molecular interactions of CDCs, along with the effective optimization of the physicochemical properties of CDC-targeted nanomaterials, holds great prospect in overcoming these challenges. Future research focusing on enhanced understanding of CDC physiological interactions and developing innovative CDC-responsive nanoplatforms for targeted delivery offers valuable prospects in advancing this field and may ultimately enable the successful clinical translation of CDC-based therapies. Despite current challenges in ongoing research, the strategic exploitation of CDCs holds significant potential in the advancement of targeted biosensing and therapeutic innovations.
A comprehensive review of thermal ablation technologies for transdermal drug delivery: mechanisms, commercial products, and future smart systems.
Murtaza M, Khan SA, Khan H … +1 more , Hossain SKS
Drug Deliv Transl Res · 2026 May · PMID 42065859 · Publisher ↗
The skin is the body's largest organ and is considered as a protective barrier which acts as a highly impermeable region of the human body. But in recent times, it is recognized as a specialized organ that aids in the de...
The skin is the body's largest organ and is considered as a protective barrier which acts as a highly impermeable region of the human body. But in recent times, it is recognized as a specialized organ that aids in the delivery of a wide range of drug molecules into the skin (intradermal drug delivery) and across the skin into systemic circulation (transdermal drug delivery, TDD). Transdermal administration remains an active research and development area as an alternative route for long- acting drug delivery. It avoids major drawbacks of conventional oral (gastrointestinal side effects, low drug bioavailability, and need for multiple dosing) or parenteral routes (invasiveness, pain, and psychological stress and bio-hazardous waste generated from needles), thereby increasing patient appeal and compliance. The bioavailability of a drug administered transdermally can be improved by several penetration enhancement techniques, which are broadly classified into chemical and physical techniques. Application of the mentioned techniques together with efforts of various scientific and innovative companies had made TDD a multibillion-dollar market and this has led to a growing market with a steady pipeline of new transdermal products receiving regulatory approval. Out of various techniques, thermal therapeutic methods including chemical heating, laser ablation, thermoporation, radiofrequency and photothermal therapy are the top listed emerging techniques. This review article mainly discussed about these thermal ablation techniques with their available commercial products along with advantages and disadvantages. This review also presented anatomy of the skin, penetration pathways across the skin, affecting factors and different generations and mechanisms of TDD. Briefly, this article discussed basics, mechanism, challenges, and future research and development directions of thermal-based TDDS.
Finding the sweet spot between complexation and cytosolic release with different molecular weight branched polyethyleneimine polymers for mRNA delivery.
Zhang H, Xiao J, Li W … +3 more , Li Q, De Smedt SC, Remaut K
Drug Deliv Transl Res · 2026 Jul · PMID 42062705 · Publisher ↗
Messenger RNA (mRNA) is a promising therapeutic for genetic defects, gene editing and vaccines. The success of mRNA therapies largely depends on the optimal delivery vehicles. Although lipid nanoparticles are the leading...
Messenger RNA (mRNA) is a promising therapeutic for genetic defects, gene editing and vaccines. The success of mRNA therapies largely depends on the optimal delivery vehicles. Although lipid nanoparticles are the leading option, some polymers exhibited attractive properties in mRNA delivery. In this study, branched polyethylene-imine (PEI) with molecular weight (Mw) of 1.8 kDa, 10 kDa and 25 kDa were explored for mRNA delivery. The complexation, dissociation and stability of bPEI/mRNA polyplexes were examined by gel electrophoresis. In vitro cellular uptake and transfection efficiency were evaluated in human cancer cell lines by using fluorescently labeled mRNA and reporter mRNA encoding enhanced green fluorescence protein. An oligonucleotide dequenching assay was used to visualize the endosomal escape of polyplexes. The mRNA full complexation started from N/P ratio 5, independent of the Mw of PEI polymers. In SKOV-3 cells, 10 kDa PEI exhibited the most promising transfection efficiency. While 1.8 kDa bPEI/mRNA polyplexes failed to escape from endosomal compartments, 25 kDa bPEI/mRNA polyplexes did endosomal escape, but less mRNA dissociation in the cytosol. In HeLa cells, cellular uptake and transfection efficiency increased through increasing either the N/P ratio or Mw of bPEI. However, the delivery efficiency of bPEI as an mRNA carrier remains relatively low and depends on balancing the appropriate Mw and N/P ratio for each specific cell type. Since cellular uptake was consistently high, the limiting factors for transfection efficiency are most likely endosomal escape and the intracellular release of functional mRNA, both of which appear to be strongly cell‑type dependent.
uPAR-targeted stealth small-sized mesoporous silica nanoparticles for pancreatic cancer therapy.
Pontón I, Núñez S, Semino C … +1 more , Sánchez-García D
Drug Deliv Transl Res · 2026 Apr · PMID 42062704 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stroma and aberrant tumor-associated vasculature, which impede nanoparticle (NP) penetration and accumulation, thereby reducing therapeutic eff...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stroma and aberrant tumor-associated vasculature, which impede nanoparticle (NP) penetration and accumulation, thereby reducing therapeutic efficacy. To overcome these barriers, small, selective NPs with prolonged circulation times are essential for effective tumor tissue penetration. In this study, mesoporous silica nanoparticles (MSNs) with a diameter of 45 nm were synthesized and coated with an albumin corona using a novel pH-sensitive "click" acetal linker. The albumin corona acts as a pH-responsive gatekeeper and scaffold, decorated with two distinct peptides: U11 and a CD47-derived "minimal peptide." The U11 peptide enables active targeting of PDAC cells, increasing NP uptake by 1.6- and 2.2-fold in MIA PaCa-2 and PANC-1 cells, respectively. The CD47-mimicry peptide promotes immune evasion, reducing macrophage uptake in RAW 264.7 cells by 2.3-fold compared to uncoated MSNs. The NPs were loaded with a camptothecin (CPT) gemcitabine (GEM) conjugate. The cytotoxicity of this pH-sensitive nanocarrier was evaluated in vitro against PANC-1 and MIA PaCa-2 pancreatic cancer cell lines.
Translatability of a miniature pig model to predict subcutaneous clinical injection times with a high-volume auto-injector and recombinant human hyaluronidase.
Connor RJ, Nekoroski T, Kang DW
Drug Deliv Transl Res · 2026 Apr · PMID 42060065 · Publisher ↗
Miniature pigs are an established preclinical model for subcutaneous (SC) drug administration; however, research on the direct translatability of this model is limited. This post hoc analysis of preclinical and clinical...
Miniature pigs are an established preclinical model for subcutaneous (SC) drug administration; however, research on the direct translatability of this model is limited. This post hoc analysis of preclinical and clinical data assessed the translatability of performance characteristics of a high-volume auto-injector (HVAI) and SC injection site outcomes from the miniature pig model to humans. An HVAI was developed to subcutaneously administer 10 mL of an antibody solution at a targeted delivery time of ~ 30 s. These rapid, high-volume injections were facilitated by co-administration with recombinant human hyaluronidase PH20. The HVAI was assessed in previous preclinical studies in miniature pigs and in a Phase I clinical trial using the same devices (syringe pump and HVAI), test solution, and injection hardware, facilitating direct comparison between injection outcomes. Injection duration and injection site outcomes (swelling, induration, erythema, back-leakage) were measured in all studies. Injection force measurements with the syringe pump in pigs versus humans allowed for the calculation of a scaling factor to model injection duration in humans (90.8%) which was used to estimate an injection time of 27.5 s with this specific HVAI configuration. Observed injection duration between the two species were similar and not statistically different (30.0 s vs 27.9 s; p = 0.17). Swelling and induration were more significant in pigs than in humans (p < 0.01), while erythema scores tended to be higher in humans than in pigs (p < 0.05). Collectively, the miniature pig is a translatable model for subcutaneous injection that can generate useful predictions of injection times in human studies and de-risk clinical trials.
Propellant-free intrawound antibiotic foam for intraoperative antimicrobial prophylaxis.
Karavasili C, Connolly ID, Park S … +9 more , Boyce H, Chang C, Guevara A, Morimoto J, Fabian N, Jimenez M, Gershanok GS, Shankar GM, Traverso G
Drug Deliv Transl Res · 2026 Jul · PMID 42050315 · Publisher ↗
Intrawound vancomycin powder is the most widely used intraoperative prophylactic intervention against surgical site infections (SSIs). However, applying raw drug powder to irregular or small surgical cavities can result...
Intrawound vancomycin powder is the most widely used intraoperative prophylactic intervention against surgical site infections (SSIs). However, applying raw drug powder to irregular or small surgical cavities can result in uneven wound coverage, drug precipitation, and airborne drug particles. To address these issues, we developed a surfactant-based aqueous foam specifically for spine surgery, where deep incisions and instrumentation heighten SSI risks. A rat model of spinal implant-associated Staphylococcus aureus infection was developed to assess the antimicrobial efficacy of intrawound vancomycin foam. The compatibility of the blank foam and the antimicrobial efficacy of the vancomycin foam were assessed in vivo in Sprague Dawley rats. Biocompatibility was evaluated by applying the foam, dispensed from a propellant-free pump device to the dorsal spine wound bed. The antimicrobial efficacy of the vancomycin foam was evaluated through exposure of the dorsal spine of the animals, foreign body implantation and S. aureus inoculation, with comparisons made to vancomycin powder-treated and untreated groups. Using a propellant-free pump device delivers the foam easily, ensuring uniform coverage and drug retention without leaving any solid residues. The foam formulation significantly increases vancomycin solubility compared to water alone. In a rat model of spinal implant-associated Staphylococcus aureus infection, the vancomycin foam demonstrated antimicrobial efficacy comparable to the vancomycin powder, with no observed soft tissue damage or systemic toxicity. Here, we have demonstrated that propellant-free aqueous foams can be an effective and simple alternative to intrawound vancomycin powder for preventing SSIs in spine surgery.
Computational insights into drug hygroscopicity by coupling machine learning and molecular simulation.
Yin X, Wang N, Zhong H … +1 more , Ouyang D
Drug Deliv Transl Res · 2026 Apr · PMID 42050314 · Publisher ↗
Hygroscopicity is one of the critical material attributes (CMAs) of active pharmaceutical ingredients (APIs), and excessive hygroscopicity can adversely affect drug manufacturability, stability, and even therapeutic effi...
Hygroscopicity is one of the critical material attributes (CMAs) of active pharmaceutical ingredients (APIs), and excessive hygroscopicity can adversely affect drug manufacturability, stability, and even therapeutic efficacy. Traditional experimental methods for measuring hygroscopicity are time- and resource-consuming, limiting their suitability for the growing demands of preformulation developability screening. Therefore, developing robust, high-throughput computational approaches to identify highly hygroscopic compounds is of great significance for drug screening, formulation design, and risk management. Here, we propose an integrated computational strategy that combines machine learning (ML) and molecular simulations for rapid prediction of drug hygroscopicity and mechanistic elucidation. A dataset comprising dynamic vapor sorption (DVS) curves for 607 drugs was first curated, based on which 8 ML algorithms representing different modeling principles were compared. Among them, Tabular Prior-data Fitted Networks (TabPFN) achieved the best performance, with an R of 0.701 ± 0.075 for regression of moisture-induced weight change (%), and accuracies of 0.741 ± 0.047 and 0.872 ± 0.029 for four-class and binary classification. SHapley Additive exPlanations (SHAP) analysis identified molecular surface area, polarity, and electrostatic descriptors as key factors influencing hygroscopicity. Building upon this insight, molecular dynamics and quantum chemical simulations further revealed that polar functional groups, hydrogen bonding, and surface conformations govern water-molecule interactions, consistent with the ML-derived insights. Overall, the effective combination of AI-driven predictions and physics-based mechanistic insights underscores the potential of this approach for preformulation developability screening and optimization, offering a promising avenue to reduce R&D costs and enhance drug development efficiency.
Cyclodextrin-based MOFs for oral delivery of fingolimod with enhanced pharmacokinetics.
Terekhova I, Garibyan A, Kalyagina T … +3 more , Delyagina E, Sapozhnikova T, Ivanov S
Drug Deliv Transl Res · 2026 Apr · PMID 42050313 · Publisher ↗
This study is aimed to improve the pharmacologically important properties of fingolimod – an immunomodulatory drug for multiple sclerosis treatment. Cyclodextrin-based metal-organic frameworks (CD-MOFs) were considered a...
This study is aimed to improve the pharmacologically important properties of fingolimod – an immunomodulatory drug for multiple sclerosis treatment. Cyclodextrin-based metal-organic frameworks (CD-MOFs) were considered as advanced biocompatible delivery systems, which are able to increase the aqueous solubility, dissolution rate and pharmacokinetics of lipophilic fingolimod. CD-MOFs synthesized on the basis of K+ cations and native α-, β- and γ-cyclodextrins differ in structure and properties. In this work, the influence of surface area, pore dimensions and particle size of CD-MOFs on their capability to fingolimod encapsulation was analyzed for the first time. It was shown that loading of fingolimod into γCD-MOF is more effective compared with αCD-MOF and βCD-MOF. Adsorption of fingolimod on all CD-MOFs under study is a physical process, mechanism of which depends on the CD-MOF porosity. Adsorption of fingolimod on βCD-MOF possessing low surface area is well described by the Langmuir model, whereas the Freundlich model better simulates the fingolimod adsorption on αCD-MOF and γCD-MOF having highly developed surface area. Crystallization of fingolimod in αCD-MOF displaying higher surface area and pore radius was detected; while the drug fully integrates into βCD-MOF and γCD-MOF, causing the disappearance of the drug crystalline phase. Loading in CD-MOF increases the thermal stability of fingolimod. Moreover, in vitro release study showed that dissolution rate of fingolimod loaded into CD-MOFs is considerably increased in phosphate buffer (pH = 6.8). The in vivo experiments showed that bioavailability of orally administrated fingolimod can be improved via encapsulation in γCD-MOF. The obtained results confirm the feasibility of CD-MOFs in design of novel dosage forms of fingolimod for oral administration.
Soft nanoparticles for chrysin delivery: an evidence mapping of nanocarrier strategies and biological applications.
da Silva ML, Araujo de Morais Trindade G, Martins de Carvalho Ragassi W … +4 more , Sari MHM, Reolon JB, Pontarolo R, Ferreira LM
Drug Deliv Transl Res · 2026 Apr · PMID 42045770 · Publisher ↗
Chrysin, a naturally occurring flavonoid found in honey, propolis, and various medicinal plants, exhibits a wide spectrum of promising pharmacological activities, including potent antioxidant, anti-inflammatory, neuropro...
Chrysin, a naturally occurring flavonoid found in honey, propolis, and various medicinal plants, exhibits a wide spectrum of promising pharmacological activities, including potent antioxidant, anti-inflammatory, neuroprotective, and anticancer properties. These therapeutic potentials are, however, severely constrained by their inherent physicochemical challenges, primarily their pronounced hydrophobicity, low stability under physiological conditions, and poor oral bioavailability, which limit their clinical translation. To overcome these barriers, nanoencapsulation has emerged as a promising strategy. This scoping review maps the existing scientific literature to synthesize evidence on how encapsulating chrysin within soft nanocarriers, such as lipid, polymeric, and protein-based nanoparticles, influences its bioavailability and therapeutic efficacy. Following PRISMA-ScR guidelines, 74 studies were included from three major databases: PubMed, Scopus, and Web of Science. The findings demonstrate that nanoformulations consistently enhance chrysin's solubility, stability, and pharmacokinetic profile, resulting in significantly greater biological effects in preclinical models across diverse applications, most notably in oncology and neuroprotection. These systems enable targeted delivery, controlled release, and improved biodistribution, such as facilitating blood-brain barrier penetration. Despite compelling preclinical evidence, the review identifies a critical translational gap, with a complete absence of clinical trials and a predominance of in vitro studies. This synthesis consolidates the current knowledge landscape and highlights the transformative potential of nanotechnology for chrysin delivery. Future research is needed to address safety, scalability, and rigorous in vivo validation to translate this promising research into real-world treatments for patients.
Synergistic role of monoacyl phospholipids and precipitation inhibitor in ternary solid dispersions: a case study of Aripiprazole.
Uparikar M, Debaje S, Guleria K … +2 more , Shaikh KA, Sangamwar AT
Drug Deliv Transl Res · 2026 Apr · PMID 42032392 · Publisher ↗
The use of phospholipids in solid dispersions represents a promising strategy for overcoming the solubility barriers of BCS Class II compounds; however, the impact of monoacyl phospholipids (MAPC) on supersaturation main...
The use of phospholipids in solid dispersions represents a promising strategy for overcoming the solubility barriers of BCS Class II compounds; however, the impact of monoacyl phospholipids (MAPC) on supersaturation maintenance requires systematic optimization. This study investigated the biopharmaceutical performance of MAPC-based binary and ternary solid dispersions, using aripiprazole as a low-solubility model drug. Binary dispersions prepared by solvent evaporation induced only partial amorphization, the integration of a precipitation inhibitor (hydroxypropyl methylcellulose phthalate, HPMCP-L55) in ternary systems proved critical, yielding fully amorphous formulations with physical stability exceeding 90 days. In vitro characterization demonstrated that the ternary dispersion enabled an ~ 85-fold increase in apparent solubility and a superior dissolution profile compared to the crystalline drug and binary dispersions. Importantly, this increase in apparent solubility was accompanied by a significant but non-proportional increase in steady-state flux (~ 4-fold) across the Permeapad® barrier, highlighting the distinction between apparent solubility enhancement and the molecularly dissolved drug fraction that governs membrane transport. Pharmacokinetic evaluation in rats further validated the platform, revealing a 6.3-fold improvement in oral bioavailability (AUC) along with rapid absorption onset. Overall, the combination of MAPC and polymeric precipitation inhibitors provides a robust strategy for stabilizing amorphous drugs, while the integrated dissolution–permeation behavior offers a mechanistically relevant predictor of in vivo performance, as supported by an exploratory IVIVC (R² = 0.9527).
Bioactive co-assembly of PSA/diT-VES nanomicelles orchestrates macrophage reprogramming for acute lung injury therapy.
Cao R, Zhou R, Wang C … +4 more , Shen M, Yu J, Xu H, Guo Z
Drug Deliv Transl Res · 2026 Apr · PMID 42032391 · Publisher ↗
Acute lung injury (ALI) is characterized by uncontrolled inflammation and oxidative stress, driven largely by macrophage dysregulation. Despite their anti-inflammatory potential, flavonoids like quercetin (Qu) are limite...
Acute lung injury (ALI) is characterized by uncontrolled inflammation and oxidative stress, driven largely by macrophage dysregulation. Despite their anti-inflammatory potential, flavonoids like quercetin (Qu) are limited by poor solubility and systemic toxicity. To address these challenges, this study developed a "bioactive co-assembly" nanomicelle platform (Qu@PSA-VES/diT-VES) based on polysialic acid (PSA) and a novel dimerized taurine-vitamin E succinate (diT-VES). Molecular docking simulations demonstrated that quercetin (Qu) exhibits an exceptionally high binding affinity for the VES hydrophobic core. Furthermore, the incorporation of diT-VES significantly enhanced the colloidal stability of the micelles through strengthened non-covalent interactions, effectively preventing disassembly during physiological circulation. Hydrophobic interactions and hydrogen bonding were identified as the primary driving forces for micellar stability. The carrier leverages PSA to specifically target the overexpressed Siglec-1 receptor on the surface of inflammatory macrophages, thereby mediating receptor-dependent endocytosis. Within the acidic and enzyme-enriched lysosomal environment, the micelles undergo pH/enzyme dual-responsive dissociation, facilitating the escape of the drug from the lysosomal barrier and its subsequent diffusion into the cytoplasm for pharmacological action. Additionally, the carrier components VES and taurine provide antioxidant and mitochondrial protection, respectively, synergizing with Qu to significantly induce the reprogramming of M1 macrophages toward the M2 phenotype in vitro. In a murine ALI model, the system demonstrated superior lung-targeting ability, significantly reducing the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in bronchoalveolar lavage fluid and alleviating pulmonary edema and neutrophil infiltration. Experimental results indicated that under a lethal ALI challenge, the 72-h survival rate of mice in the treatment group was significantly increased from 16.7% to 83.3%, while maintaining excellent in vivo biocompatibility. This integrated "targeting-stabilization-synergy" nanoplatform provides a promising translational strategy for the treatment of macrophage-driven inflammatory disorders.
Silica based nanocarriers for combination immunotherapy targeting the tumor immune microenvironment.
Shamim S, Singh AP, Sharma H … +3 more , Gohri S, Taumar D, Chaudhary V
Drug Deliv Transl Res · 2026 Apr · PMID 42029811 · Publisher ↗
Modern oncology has been transformed by cancer immunotherapy, but it has not yet consistently delivered clinical benefits due to complex immune evasion within the tumor microenvironment. It is also becoming apparent that...
Modern oncology has been transformed by cancer immunotherapy, but it has not yet consistently delivered clinical benefits due to complex immune evasion within the tumor microenvironment. It is also becoming apparent that single therapy or immunotherapy is no longer adequate to overcome the multifactorial webs of immunosuppression in most solid tumours, and that rational combination approaches are required. Nanotechnology’s use in delivery mechanisms has emerged as a promising approach to enhance therapeutic precision, bioavailability, and immunomodulation. Notably, nanocarriers consisting of mesoporous surface-functionalized silica nanoparticles are especially beneficial, due to a high drug-loading capacity, a programmable pore architecture, structural stability, and a versatile surface chemistry. This review critically examines the design and immunological application of silica nanocarriers in cancer immunotherapy. Tumor immune evasion mechanisms and silica platforms in antigen-presenting cells targeting, tumor-associated macrophage reprogramming, localized immune checkpoint regulation, and T-cell stimulation are mentioned. The translational issues, design, and future prospects of silica-enabled immunonanomedicine are also brought to the forefront to provide a balanced, forward-looking perspective on their potential for reprogramming the immune microenvironment.
High-strength silk fibroin microneedles for transdermal colchicine delivery: a dose-response analysis demonstrating superior efficacy over oral administration.
Chen J, Qiu G, Jiang N … +2 more , Guo B, Qiu Y
Drug Deliv Transl Res · 2026 Apr · PMID 42029810 · Publisher ↗
Oral colchicine remains a first-line therapy for acute gout arthritis. However, its clinical utility is limited by an extremely narrow therapeutic window and the frequent onset of dose-limiting gastrointestinal toxicity....
Oral colchicine remains a first-line therapy for acute gout arthritis. However, its clinical utility is limited by an extremely narrow therapeutic window and the frequent onset of dose-limiting gastrointestinal toxicity. To overcome these challenges, we developed high-strength silk fibroin separable microneedles (HSF SMNs) for transdermal colchicine delivery. The microneedles were fabricated from regenerated silk fibroin pre-modified with methanol vapor to enhance mechanical properties. Fourier-transform infrared spectroscopy and mechanical tests showed that treating the silk fibroin solution for 30 min induced substantial β-sheet formation, yielding HSF SMNs with a fracture force of 3.01 N per needle. In vitro permeation studies demonstrated that colchicine-loaded HSF SMNs exhibited a significantly higher transdermal flux compared to an aqueous solution. Notably, the system maintained 84.3% of its initial transdermal flux at 12 h after backing layer separation, indicating robust sustained-release capability. In a rat model of acute gouty arthritis, transdermal administration of HSF SMNs at low, medium, and high doses effectively suppressed paw swelling and reduced serum levels of IL-1β and TNF-α in an administered dose-dependent manner. Importantly, the therapeutic efficacy was superior to that achieved via oral gavage. To our knowledge, this work provides the first systematic dose-response analysis for transdermal colchicine delivered via microneedles, offering a promising non-oral alternative and supporting further development of this strategy.
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