Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
Oleyl-hyaluronate nanoparticles for enhanced peroral bioavailability of encapsulated Coenzyme Q10.
Juhaščik M, Fiala F, Čožíková D … +7 more , Vágnerová H, Kulhánek J, Kocurková A, Šimek M, Stránská A, Kubala L, Ondreáš F
Drug Deliv Transl Res · 2026 Apr · PMID 41946825 · Publisher ↗
Hyaluronic acid (HA) is a biocompatible, mucosal-interacting polysaccharide that offers unique advantages for oral drug delivery. Chemical modification with hydrophobic groups transforms HA into an amphiphilic polymer ca...
Hyaluronic acid (HA) is a biocompatible, mucosal-interacting polysaccharide that offers unique advantages for oral drug delivery. Chemical modification with hydrophobic groups transforms HA into an amphiphilic polymer capable of self-assembly and encapsulation of poorly soluble compounds. In this work, we developed an oral delivery system based on oleyl-hyaluronate (O-HA) for coenzyme Q10 (CoQ10), a lipophilic antioxidant with limited solubility and low bioavailability. The coenzyme Q10-loaded oleyl-hyaluronate nanoparticles (O-HAQ10) were prepared using a multistep solvent evaporation method, achieving a high CoQ10 loading of up to 13.8 g/L and an encapsulation efficiency typically exceeding 90%. Crucially, this platform achieved an exceptionally high drug loading capacity, substantially minimizing the surfactant burden typically required to stabilize highly lipophilic payloads. The nanoparticles exhibited nanoscale dimensions (200-300 nm), as confirmed by dynamic light scattering (DLS) and scanning electron microscopy (SEM). Comprehensive in vitro evaluation confirmed robust cytocompatibility with the Caco-2 human intestinal epithelial cell line. Furthermore, studies on porcine intestine demonstrated significantly enhanced mucosal accumulation compared to commercial liposomal and oil-based formulations, even following simulated gastric exposure. In vivo pharmacokinetic evaluation in mice confirmed a 72% increase in systemic bioavailability relative to the clinical gold-standard oil-based control. These findings highlight the potential of hydrophobically modified HA as a highly efficient, versatile platform for the peroral delivery of poorly soluble bioactives.
Repurposing felodipine via hyaluronic acid-coated cetylosomes (HCCs) for parenteral active targeting of cancer: Box-Behnken statistical optimization, in vitro characterization, and in vivo studies.
El-Dahmy RM, Eltabeeb MA, Fayez SM … +4 more , El-Emam SZ, Adl NME, Saber MM, Fahmy AM
Drug Deliv Transl Res · 2026 Apr · PMID 41941056 · Publisher ↗
Felodipine (FEL), an antihypertensive drug, is being repurposed as an anticancer drug. It has low oral bioavailability due to its extensive metabolism in the liver and poor water solubility. This study aimed to develop h...
Felodipine (FEL), an antihypertensive drug, is being repurposed as an anticancer drug. It has low oral bioavailability due to its extensive metabolism in the liver and poor water solubility. This study aimed to develop hyaluronic acid-coated cetylosomes (HCCs) for parenteral delivery of FEL to boost its solubility and anticancer efficacy. FEL-HCCs were prepared by the thin-film hydration technique based on Box-Behnken design. Amounts of cetyl alcohol, Brij 97, and hyaluronic acid were the independent factors. The optimized HCC (OHCC) formula which showed the highest desirability value (0.626), was composed of 100 mg Brij 97, 32.44 mg CA, and 10 mg HA. It showed the minimum vesicle size (156.72 nm) and polydispersity index (0.134), and the maximum entrapment efficiency% (72.04%) and zeta potential (-30.58 mV). After lyophilization and sterilization of the OHCC formula, it showed a 2.01-fold enhancement in FEL release compared to the market tablet, with no significant difference in release before and after lyophilization or sterilization. The sterilized OHCC was stable for six months. The OHCC showed an enhanced cytotoxicity against MCF-7 cells with 6.61-fold compared to pure FEL powder. Additionally, the OHCC potentiated the antiproliferative effect of doxorubicin, as evidenced by a raised Bax/Bcl-2 ratio and caspase 9 content, and suppressed VEGF levels. In vivo, the OHCC markedly reduced tumor growth, particularly in combination with doxorubicin. The histopathological investigation supported the apoptotic and necrotic death of cancer cells. These findings suggest that HCCs represent a promising nanocarrier system for the targeted parenteral delivery of FEL in cancer therapy.
Nanoemulsion-based colistin for pulmonary delivery: Enhanced antibacterial efficacy against Acinetobacter baumannii.
Martínez-Guitián M, Sanjurjo L, Vázquez-Ucha JC … +4 more , Muras A, Beceiro A, Crecente-Campo J, Alonso MJ
Drug Deliv Transl Res · 2026 Jul · PMID 41912855 · Full text
Infections caused by Acinetobacter baumannii, which frequently result in pneumonia and/or bacteraemia, represent a significant clinical challenge. Colistin, an antimicrobial peptide used as a last-resort therapy due to i...
Infections caused by Acinetobacter baumannii, which frequently result in pneumonia and/or bacteraemia, represent a significant clinical challenge. Colistin, an antimicrobial peptide used as a last-resort therapy due to its high toxicity, is employed to treat severe infections, i.e. those caused by A. baumannii. The aim of this study was to develop a colistin-loaded nanoformulation (COL-NE) capable of targeting infected cells in the lung, thereby enhancing antibacterial efficacy while reducing toxicity. After screening multiple formulations, an optimized colistin nanoemulsion (COL-NE) was developed, exhibiting a particle size of 180 nm and a 1-4-fold reduction in MIC against A. baumannii compared to free colistin. The nanoemulsion also displayed significant antibiofilm activity, enhanced cellular penetration, and a 27-45% reduction in in vitro toxicity relative to colistin. Notably, following intratracheal administration, COL-NE improved the elimination of intracellular bacteria in macrophages through passive targeting while maintaining activity against extracellular bacteria. In a murine pneumonia model, COL-NE reduced lung bacterial burden by 2 log₁₀ CFU/mL compared with untreated controls and by 1.25 log₁₀ CFU/mL relative to colistin-treated mice. These findings highlight the potential of colistin-loaded nanoemulsions as a promising therapeutic strategy against A. baumannii infections, enhancing antibacterial efficacy while mitigating colistin-associated toxicity.
Treatment of myocardial infarction via implantation of electroactive alginate/gelatin cardiac patch seeded with mesenchymal stem cells in a rat model.
Behzadi E, Baheiraei N, Naderi N … +1 more , Nemati F
Drug Deliv Transl Res · 2026 Mar · PMID 41903101 · Publisher ↗
Myocardial infarction (MI) is a leading cause of mortality around the globe. Cardiac patches offer a promising tissue engineering approach to facilitate the natural regeneration of damaged cardiac tissue. In this researc...
Myocardial infarction (MI) is a leading cause of mortality around the globe. Cardiac patches offer a promising tissue engineering approach to facilitate the natural regeneration of damaged cardiac tissue. In this research, electroactive cardiac patches composed of alginate-gelatin (Alg-Gel) were fabricated using a freeze-drying technique. The scaffolds were subsequently coated with varying concentrations of reduced graphene oxide (rGO) to improve cardiac performance. The samples were thoroughly characterized in terms of their physicochemical, morphological, and biological properties, including morphology, cell viability, and gene expression. Notably, an rGO concentration of 0.3% w/v significantly improved the viability of bone marrow-derived mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs), while upregulating the expression of Connexin 43 (Conx43), tryptophan transporter 2 (TrpT-2), and actinin 4 (Actn4), all of which are critical for cardiac cell function. To evaluate therapeutic efficacy in vivo, Alg-Gel-rGO scaffolds seeded with BMSCs were implanted into the infarcted area of a rat model of MI. Echocardiographic, histological, and immunohistochemical analyses demonstrated that the prepared patches improved cardiac function, reduced scar thickness, and promoted angiogenesis, thereby supporting cardiac tissue repair. These findings suggest that Alg-Gel-rGO scaffolds hold significant potential for regenerating damaged myocardial tissue and enhancing post-MI recovery, representing a viable strategy in cardiac tissue engineering.
Nail tattooing: a novel and minimally invasive technique for enhancing drug penetration through the nail.
Bendicho-Lavilla C, Díaz-Tomé V, Seoane-Viaño I … +2 more , de-Monte-Vidal V, Otero-Espinar FJ
Drug Deliv Transl Res · 2026 Mar · PMID 41888505 · Publisher ↗
Onychomycosis, a prevalent fungal infection, and psoriasis, a chronic immune disorder affecting the nail plate, present therapeutic challenges due to the limited efficacy of current treatments, often leading to prolonged...
Onychomycosis, a prevalent fungal infection, and psoriasis, a chronic immune disorder affecting the nail plate, present therapeutic challenges due to the limited efficacy of current treatments, often leading to prolonged therapy and a high relapse rate. The highly cross-linked keratin network of the nail plate acts as a barrier, impeding effective drug delivery. This pioneering study explores a novel approach using a tattoo device to enhance drug penetration through the nail. Ciclopirox olamine and clobetasol lacquers were selected as the model formulations. Drug permeation tests conducted on non-treated, filed (mechanically abraded), and tattooed nails demonstrated significantly higher drug permeation in tattooed nails, suggesting the potential of this delivery method. Nail tattooing offers a simple method to enhance topical therapy, allowing treatment initiation in the clinic and continuation at home.
Recent advances in interstitial fluid dynamics for diagnostic, targeted drug delivery and precision medicine applications.
Somandi K, Kulati H, Holman DE … +4 more , Abrahams AI, Ngoepe MP, Keyster M, Choonara YE
Drug Deliv Transl Res · 2026 Mar · PMID 41888504 · Publisher ↗
Interstitial fluid (ISF), the extracellular fluid surrounding tissue cells, has emerged as a promising biofluid for biomarker detection and localized physiological monitoring. Although its clinical use remains limited co...
Interstitial fluid (ISF), the extracellular fluid surrounding tissue cells, has emerged as a promising biofluid for biomarker detection and localized physiological monitoring. Although its clinical use remains limited compared with blood or urine, advances in minimally invasive extraction technologies have expanded research interest in its diagnostic and therapeutic potential. ISF shares biochemical similarities with blood but is more accessible through minimally invasive techniques, offers localized biomarker concentrations, and avoids clotting issues. Recent research has demonstrated that ISF contains a rich profile of biomolecules, including proteins, nucleic acids, metabolites, and cytokines, that are valuable for diagnosing and managing a variety of conditions such as infections, metabolic disorders, cancers, and neurological diseases. Advances in microneedle (MN) technology, wearable biosensors, and minimally invasive extraction methods have enabled the efficient sampling and analysis of ISF, bringing its clinical applications closer to reality. Beyond diagnostics, ISF is now being leveraged in therapeutic applications, particularly in precision medicine and drug delivery. Novel delivery strategies such as MNs, convection-enhanced delivery (CED), electroosmotic flow, and fiber-optic theranostics use ISF as both a conduit and a target environment, especially for conditions like solid tumors, where interstitial fluid pressure (IFP) plays a critical role in treatment efficacy. Simulated ISF models are also being developed to facilitate preclinical drug testing and improve translational success. This review emphasizes the mechanistic physiology of ISF from both human and preclinical/animal models, including its pressure regulation, transport dynamics, and simulated/computational modelling, as the foundation for next-generation drug delivery design. While diagnostic and sampling technologies are summarized for context, the review primarily explores how ISF dynamics guide targeted therapy and precision medicine. Overall, ISF offers a dynamic and responsive medium for next-generation medical applications, combining real-time physiological insight with localized therapeutic action. Furthermore, current research and technological advancements, emphasizing the transformative potential of ISF to bridge diagnostics, personalized therapy, as well as drug development and targeted delivery are reviewed herein.
Intra-articular dual-targeted hydrogel co-delivering diacerein nanoparticles and ketorolac for modulating neuroimmune interplay and cartilage degeneration in osteoarthritis.
Heikal LA, Abdel Nasser MG, El-Mezayen NS … +3 more , Farid RM, Etman MA, Elkamary YM
Drug Deliv Transl Res · 2026 Mar · PMID 41874937 · Publisher ↗
Osteoarthritis (OA) is a multifactorial joint disease characterized by cartilage degradation, chronic inflammation, and persistent pain, yet current treatments provide only symptomatic relief without altering disease pro...
Osteoarthritis (OA) is a multifactorial joint disease characterized by cartilage degradation, chronic inflammation, and persistent pain, yet current treatments provide only symptomatic relief without altering disease progression. This study aimed to develop and evaluate an intra-articular co-delivery system of diacerein (DC) using solid lipid nanoparticles (SLN) and ketorolac (KT) incorporated into a hydrogel matrix (DC-SLN gel) for synergistic cartilage protection and pain relief. SLN were optimized for particle size and polydispersity index by central composite design. In addition to zeta potential, entrapment efficiency, DSC, TEM, and stability assessment. The hydrogel composed of xanthan gum and sodium hyaluronate was characterized for rheological and in vitro release studies. In vitro release studies confirmed sustained DC release for prolonged chondroprotection and rapid KT release for acute analgesia. Therapeutic efficacy was evaluated in MIA-induced OA rats through behavioral assays, histological scoring, biochemical markers, and molecular analyses of inflammatory and chondrogenic pathways. DC-SLN/KT.gel demonstrated superior outcomes compared to free drugs or single-drug formulations. It significantly reduced pain behaviors, suppressed NF-κB, IL-1β, CCL2, and Substance P, and lowered CD68⁺ macrophage infiltration. Concurrently, it preserved collagen II, inhibited MMP-13, and upregulated SOX-9 and miR-140, restoring cartilage homeostasis. In conclusion, embedding SLN within an injectable hydrogel enabled targeted, site-specific, and sustained intra-articular drug delivery, reducing systemic exposure while enhancing efficacy. These results demonstrate the DC-SLN gel as a promising translational platform that unites targeted pain management with disease-modifying potential for advanced OA therapy.
Preparation and evaluation of citalopram novasomal vesicles as a transdermal analgesic drug delivery.
Haftan F, Morteza-Semnani K, Akbari J … +3 more , Seyedabadi M, Ghasemi M, Saeedi M
Drug Deliv Transl Res · 2026 Mar · PMID 41874936 · Publisher ↗
The objective of this study was to enhance the transdermal delivery of citalopram HBr (CTP) by incorporating it into novasomes (Citalosomes) prepared via probe sonication. Previous studies have shown limited transdermal...
The objective of this study was to enhance the transdermal delivery of citalopram HBr (CTP) by incorporating it into novasomes (Citalosomes) prepared via probe sonication. Previous studies have shown limited transdermal absorption and short-term therapeutic effects of conventional citalopram formulations, representing a research gap that this study aims to address. The influence of cholesterol-to-surfactant ratio and oleic acid content on formulation characteristics was investigated. Particle size, zeta potential, and entrapment efficiency (EE%) were assessed using dynamic light scattering (DLS) and UV-spectrophotometry, respectively. Results showed that increasing cholesterol concentration enhanced vesicle rigidity and structural characteristics but reduced EE%. Meanwhile, optimizing the oleic acid to surfactant ratio improved membrane fluidity and significantly increased encapsulation efficiency. The optimized novasomal vesicle formulation (Citalosome 2) exhibited a vesicle size of 282.66 ± 5.85 nm, PDI 0.228 ± 0.028, zeta potential of 9.1 ± 0.26 mV, and EE% of 36.42 ± 2.09. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and differential scanning calorimetry (DSC) analysis confirmed the presence of the drug in an amorphous state without any chemical interaction within the formulation. Transmission electron microscopy (TEM) images demonstrated spherical morphology and suitable dispersion of vesicles. In vitro skin permeation studies using a carbopol-based gel indicated higher transdermal absorption of the drug from Citalosome 2 gel compared to plain CTP gel (p < 0.05). The Citalosome system also showed a sustained release profile over 24 h. Cytotoxicity evaluation on HFF cells confirmed low toxicity (> 88% viability). Furthermore, in vivo analgesic and anti-inflammatory assessments (hot-plate, formalin, and paw edema tests) using the same carbopol-based gel revealed prolonged and improved antinociceptive and anti-inflammatory responses of Citalosome 2 gel compared to control formulations (p < 0.05). Histological analysis demonstrated decrease in inflammation following topical application. These findings suggest that Citalosome 2 may serve as a promising vesicular carrier for transdermal citalopram delivery, with the potential to improve its analgesic efficacy.
Formulation considerations in enhancing olfactory mucosal deposition for nose-to-brain drug delivery.
DSouza AA, Kahan M, Yang A … +3 more , Padmakumar S, Bleier BS, Amiji MM
Drug Deliv Transl Res · 2026 Mar · PMID 41865231 · Publisher ↗
Nose-to-brain (N2B) drug delivery offers a promising alternative to circumvent the blood-brain barrier and deliver therapeutic agents directly to the central nervous system. Among the intranasal pathways, targeting the o...
Nose-to-brain (N2B) drug delivery offers a promising alternative to circumvent the blood-brain barrier and deliver therapeutic agents directly to the central nervous system. Among the intranasal pathways, targeting the olfactory mucosa is particularly attractive due to its direct anatomical and functional connection to the brain. However, effective deposition and retention of drug-loaded formulations in the olfactory region remain significant challenges, owing to complex nasal anatomy, mucociliary clearance, and limited surface area. This review critically examines the physiological and anatomical barriers to olfactory targeting and highlights recent advances in nanoparticle-based strategies designed to enhance mucosal deposition and transport. Various formulation approaches-including mucoadhesive polymers, surface-functionalized nanocarriers, and stimuli-responsive systems-are discussed alongside innovative delivery devices and administration techniques tailored for olfactory mucosal delivery. In vitro, ex vivo, and in vivo models used to evaluate these strategies are reviewed, as are safety, regulatory, and translational considerations. Finally, the review explores emerging technologies such as patient-specific delivery platforms and smart nanoparticles, offering a forward-looking perspective on the future of N2B therapeutics for neurological disorders.
Iloprost-loaded inhalable Nano into Micro (NiM) formulations for treating hyper-inflammation in a pre-clinical model of cystic fibrosis airway epithelial cells.
Carbone A, Soccio P, Craparo EF … +11 more , Vitullo P, Bonsignore S, Tondo P, Scialabba C, Sajid N, Jahani S, Drago SE, Di Gioia S, Lacedonia D, Cavallaro G, Conese M
Drug Deliv Transl Res · 2026 Mar · PMID 41865230 · Publisher ↗
To address the hyper-inflammation associated with cystic fibrosis (CF) lung disease, we evaluated the efficacy of inhalable Nano into Micro (NiM) formulations carrying a repurposed anti-inflammatory agent, i.e. Iloprost...
To address the hyper-inflammation associated with cystic fibrosis (CF) lung disease, we evaluated the efficacy of inhalable Nano into Micro (NiM) formulations carrying a repurposed anti-inflammatory agent, i.e. Iloprost (ILO), a prostacyclin analogue. Nasal epithelial brushings were obtained from 15 individuals with CF bearing at least one F508del mutation. The isolated cells were expanded using the conditional reprogramming culture method and subsequently differentiated into a mucociliary epithelium at air-liquid interface (ALI) cultures capable of producing endogenous mucus. ALI cultures were exposed to lipopolysaccharide (LPS), either alone or in combination with NiM formulations - entrapping pegylated or non-pegylated nanoparticles - carrying ILO (named NiM-PEG-ILO and NiM-ILO, respectively). The treatment with NiM-PEG-ILO significantly reduced mRNA levels of the pro-inflammatory cytokines TNF-α, IL-6, IL-8, and IL-1β compared to LPS stimulation alone. Furthermore, a marked downregulation of miR-145, miR-146a, and miR-17 levels was observed relative to the LPS-only group. Cytofluorimetry analysis carried out by using NiM samples entrapping fluorescent pegylated and unpegylated nanoparticles loaded with ILO showed that both nanoparticles NiM formulations were internalized by cells in a concentration-dependent manner. Our results demonstrate that inhalable NiM-based formulations delivery system loaded with ILO can efficiently attenuate inflammation in a pre-clinical model of human airway epithelium.
Rectal nanoparticulate-hydrogel delivering budesonide to reduce enterohepatic drug metabolism and clearance.
Zhang RX, Lu W, Yan X … +8 more , Deng X, Wan R, Song Z, Liang J, Wang XT, Cao T, Chen Y, Tam PKH
Drug Deliv Transl Res · 2026 Mar · PMID 41862670 · Publisher ↗
Precise dosing is critical for effective therapeutics, yet extensive enterohepatic metabolism poses a major barrier to many orally administered small-molecule drugs. Budesonide, a potent corticosteroid for treating enter...
Precise dosing is critical for effective therapeutics, yet extensive enterohepatic metabolism poses a major barrier to many orally administered small-molecule drugs. Budesonide, a potent corticosteroid for treating enterohepatic inflammation, undergoes significant first-pass metabolism by cytochrome P450 3A abundantly expressed in the liver and intestine, resulting in variable efficacy and unpredictable toxicity. Rectal drug delivery offers an alternative route that can reduce first-pass metabolism. This work aimed to alter enterohepatic metabolism and clearance of budesonide using a rectal nanoparticles-hydrogel system for localized drug delivery. Budesonide was encapsulated into nanostructured lipid carrier (BD-LNP), which were then entrapped in a dynamic boronate ester crosslinked hydrogel (BD-LNP@Hydrogel). The hydrogel network exhibited thermal and mechanical stability, maintaining a drug depot post-injection, while BD-LNP was released in a controlled manner upon hydrogel degradation in simulated colonic fluid. BD-LNP@Hydrogel achieved a permeability coefficient > 1 × 10 cm·s across human intestinal epithelial monolayers, indicating completed absorption of budesonide. Compared to BD-LNP alone, BD-LNP@Hydrogel provided 4.3-fold higher nanoparticle exposure in the colonic lumen, enhancing intestinal uptake into deeper mucosal layer (e.g., lamina propria) over time. Pharmacokinetic analysis in mice revealed that rectal BD-LNP@Hydrogel markedly reduced formation of the budesonide metabolite 16α-hydroxyprednisolone compared to the oral route. Physiologically-based pharmacokinetic modeling confirmed preferential pharmacokinetics for rectal BD-LNP@Hydrogel over oral delivery, including up to 7.3-fold higher absorption rate constant, superior intestinal transport, and significantly reduced enterohepatic clearance of 16α-hydroxyprednisolone. These findings highlight the potential of nanoparticles-hydrogel systems for rectal delivery of drugs with extensive metabolism and provide mechanistic insight into achieving therapeutic precision via rectal delivery.
Endoplasmic reticulum stress induced autophagy alters cellular processing of cationic lipid delivered siRNAs.
Splichal RC, Chan C, Walton SP
Drug Deliv Transl Res · 2026 Mar · PMID 41843022 · Publisher ↗
siRNA therapeutics have achieved increased clinical success in the past decade. To achieve a therapeutic effect, siRNAs must enter the cytoplasm of the target cells. Thus, their function typically relies on proper endocy...
siRNA therapeutics have achieved increased clinical success in the past decade. To achieve a therapeutic effect, siRNAs must enter the cytoplasm of the target cells. Thus, their function typically relies on proper endocytosis and trafficking. Endoplasmic reticulum (ER) stress is associated with diseases that are being studied for treatment with siRNAs (cancer, amyloids, mutations, etc.) and common comorbidities (obesity, smoking, hypertension, etc.). ER stress results in activation of the Unfolded Protein Response (UPR), which initiates changes in cellular function that include disruption to endosomal vesicle trafficking and processing. We used the N-glycosylation inhibitor, tunicamycin, to induce ER stress in HeLa cells during transfection with siRNAs targeting EGFP. Our results showed that ER stress resulted in an increased accumulation of siRNA but a reduction in silencing of the siRNA target (EGFP). Further, we used 3-methyladenine (autophagy inhibitor) and bafilomycin A1 (inhibits endosome maturation) to show that autophagy plays a role in increasing siRNA accumulation. Finally, we showed that the additional accumulated siRNA in ER-stressed cells remained functional, was retained in cells for longer, and prolonged silencing. Our results will inform the design of siRNA delivery vehicles and dosing schedules, by ensuring that disease complications, specifically ER stress/UPR activation, are considered.
Ink to innovation: Pioneering printing technologies for next-generation drug delivery systems.
Ghazi NF, Taresco V, Jacob PL … +3 more , Monkgogi T, Burley JC, Bebawy G
Drug Deliv Transl Res · 2026 Mar · PMID 41840190 · Publisher ↗
Inkjet printing has emerged as a revolutionary technology in pharmaceutical manufacturing, offering unprecedented precision in the deposition of active pharmaceutical ingredients (APIs) and excipients. Its ability to acc...
Inkjet printing has emerged as a revolutionary technology in pharmaceutical manufacturing, offering unprecedented precision in the deposition of active pharmaceutical ingredients (APIs) and excipients. Its ability to accurately dispense nano- to picolitre volumes without direct contact with the substrate enables the development of complex and highly uniform dosage forms. This technology is uniquely positioned to overcome many limitations of conventional manufacturing processes, especially in the development of personalised and controlled-release formulations. In this review, we provide a comprehensive analysis of the principles, mechanisms, and advancements in inkjet printing technology for pharmaceutical applications. The review covers an overview of the fundamentals of inkjet printing, including drop-on-demand systems, thermal and piezoelectric printing modalities, and the critical parameters that govern droplet formation. We then examine its diverse applications, ranging from studying drugs in solid states to the production of novel formulations and personalised dosage forms. In addition, the integration of inkjet printing with advanced analytical tools is discussed, which has improved quality control and enabled high-throughput screening of drug formulations. Challenges related to ink formulation and process reproducibility are also critically evaluated, providing insights into current limitations and potential strategies for overcoming them. Finally, inkjet printing represents a transformative approach in pharmaceutical formulation development, offering scalability, flexibility, and the potential for on-demand manufacturing of patient-specific therapies. As research continues to refine inkjet printing processes and overcome existing technical challenges, this technology is poised to significantly enhance drug delivery performance and accelerate the transition toward personalised medicine. This review underscores the critical role of inkjet printing in redefining pharmaceutical technology and highlights its promising future in advancing next-generation drug delivery systems.
Ginkgolide B-cyclodextrin inclusion complexes: an encapsulation strategy for improved solubility and aerosol inhalation therapy in bronchial asthma.
Wang Y, Wei M, Zhang Y … +8 more , Liu Y, Bi X, Fan X, Gou J, He H, Tang X, Zhang Y, Yin T
Drug Deliv Transl Res · 2026 Mar · PMID 41826785 · Publisher ↗
Bronchial asthma represents a long-term inflammatory reaction in the airways, marked by the accumulation of eosinophils. Ginkgolide B (GB), derived from ginkgo biloba, serves as a potent natural antagonist of platelet ac...
Bronchial asthma represents a long-term inflammatory reaction in the airways, marked by the accumulation of eosinophils. Ginkgolide B (GB), derived from ginkgo biloba, serves as a potent natural antagonist of platelet activating factor (PAF). It can greatly reduce the production and release of eosinophils while minimizing the infiltration of other inflammatory cells in the airways, thus contributing to the management of bronchial asthma. However, due to its low bioavailability caused by poor water solubility and inherent bitter taste, it's hard for Ginkgolide B to meet the standards required for effective treatment of asthma. In this study, we developed two cyclodextrin derivatives of Ginkgolide B, namely GB-SBE-β-CD and GB-HP-γ-CD, for the therapy of bronchial asthma through aerosol inhalation. Both SBE-β-CD and HP-γ-CD effectively capsulated the Ginkgolide B. Molecular docking analysis revealed the spatial structure of GB-SBE-β-CD and GB-HP-γ-CD, highlighting hydrogen bonding as the primary driving force behind their formation. In vitro cell assays demonstrated that both Ginkgolide B and Ginkgolide B-cyclodextrin inclusion compounds exhibited good safety and potent anti-inflammatory activity. In addition, inhalation of aerosolized GB-SBE-β-CD and GB-HP-γ-CD markedly alleviated the symptoms of OVA-induced asthma in BALB/c mice, lowering infiltration of inflammatory cells, and significantly contributing to asthma treatment. The current findings suggest that the inhalation of Ginkgolide B-cyclodextrin represents a safe and promising option for managing bronchial asthma.
Advancement in therapeutic application of quantum dots in amyotrophic lateral sclerosis: current opportunities and challenges.
Bakshi V, Pathak B, Majie A … +10 more , Ghosh A, Gupta A, Jain N, Pandey M, Nair AB, Jacob S, Mazumder PM, Sharma N, Kumari N, Gorain B
Drug Deliv Transl Res · 2026 Mar · PMID 41817655 · Publisher ↗
Despite advancements in healthcare settings in developed countries, the early detection and higher mortality rate associated with amyotrophic lateral sclerosis (ALS), a fatal motor neuronal disorder, remain challenging....
Despite advancements in healthcare settings in developed countries, the early detection and higher mortality rate associated with amyotrophic lateral sclerosis (ALS), a fatal motor neuronal disorder, remain challenging. Recently, quantum dots (QDs) have emerged as a promising nanocarrier in the prognosis and treatment of ALS owing to their unique multifunctional properties. QDs, through their photoluminescence properties upon excitation, can facilitate the identification and real-time monitoring of disease biomarkers. They also act as a nanocarrier for the targeted delivery of therapeutics, avoiding accumulation at the non-targeted sites and minimising toxicity. QDs can be fabricated to conjugate with protein biomarkers linked to ALS, such as specific proteins, nucleic acids, or genetic variants, for the diagnosis of the disease. Such fabrication could lead to enhanced identification and diagnostic patterns of ALS, thereby contributing to improved therapeutic intervention strategies. Furthermore, these tiny structures could be applied in combined biosensor formats to identify ALS-associated biomarkers in body fluids, which would be a highly sensitive diagnostic system. Subsequently, comprehensive multiomics techniques have demonstrated improved identification of newer protein targets associated with neurological complications. Overall, QDs can be explored as a potential tool to identify biomarkers relevant to ALS, diagnose the disease at its early stages, and track the effectiveness of the treatment. The integration of QD with omic-based strategies and network analysis can potentially catalyse a breakthrough in the management of ALS. Therefore, this review aims to explore the application of QDs in ALS diagnosis and management, advancements in research, clinical trials, and patents.
Development of EL/PLGA nanoparticles for oral delivery of methotrexate with enhanced bioavailability and reduced toxicity.
Wu X, Zhang Q, Zeng X … +4 more , Qian P, Gao X, Jiang D, Chen H
Drug Deliv Transl Res · 2026 Mar · PMID 41814058 · Publisher ↗
For rheumatoid arthritis (RA), low-dose methotrexate (MTX) is first-line therapy but limited by gastrointestinal irritation, low bioavailability, and systemic toxicity. Herein, EL/PLGA nanoparticles loaded with MTX (MTX@...
For rheumatoid arthritis (RA), low-dose methotrexate (MTX) is first-line therapy but limited by gastrointestinal irritation, low bioavailability, and systemic toxicity. Herein, EL/PLGA nanoparticles loaded with MTX (MTX@EL/PLGA NPs) were prepared via double emulsion solvent evaporation method and evaluated in vitro and in vivo. Optimized NPs had uniform morphology with particle size of (140.3 ± 2.01) nm and zeta potential of (-30.53 ± 1.79) mV. Compared with free MTX, MTX@EL/PLGA NPs exhibited pH-responsive release in vitro, which minimized drug leakage in simulated gastric fluid and achieved efficient release in simulated intestinal fluid. In vivo, these NPs increased relative bioavailability by 195.07% with sustained plasma concentrations, accompanied with mitigated MTX-induced gastrointestinal damage and hematotoxicity without liver/kidney impairment. This study demonstrated that MTX@EL/PLGA NPs improved oral bioavailability and safety of MTX, a promising oral nano-delivery system for rheumatoid arthritis therapy.
Overcoming the oral delivery challenges of venetoclax: advancing a clinically improved Bcl-2 inhibitor.
Hegishte Y, Joyce P, Prestidge C … +1 more , Bremmell K
Drug Deliv Transl Res · 2026 Mar · PMID 41806106 · Publisher ↗
The Bcl-2 inhibitor, Venetoclax, is a notable example of a therapeutic emerging from modern drug development pipelines with structural and physiochemical properties sitting beyond Lipinski's "Rule of 5". The classificati...
The Bcl-2 inhibitor, Venetoclax, is a notable example of a therapeutic emerging from modern drug development pipelines with structural and physiochemical properties sitting beyond Lipinski's "Rule of 5". The classification of VTX as a biopharmaceutical classification system (BCS) Class IV compound aligns with its observed low solubility and permeability in the gastrointestinal tract. Its inherent "brick-dust" properties further limit solubility in lipid delivery vehicles, collectively constraining its maximum potential for oral absorption. With a low fasted oral bioavailability (< 5%) and a fivefold positive food effect, a clinical dose of 600 mg is required daily and is prescribed to patients with a meal to ensure therapeutic efficacy. The impact of critical formulation design parameters on the performance of previously reported formulation strategies such as amorphous solid dispersions, nanocrystals and lipid-based systems will be examined. Mechanistic insight into how bio-enabling strategies improve oral absorption of VTX is provided, including enhanced solubility in lipid vehicles, improved solubilisation upon dispersion, mitigation of the gastrointestinal pH gradient, reduced particle size, amorphous state enhanced-solubility and reduced metabolism. Potential alternative formulation strategies such as inorganic vehicles or advanced lipid-based systems are reviewed, with their capability to enhance VTX's bioavailability whilst reducing the high clinical dose and dependence on food for optimal absorption. Key silica and polymer selection is necessary for loading VTX mesoporous silica nanoparticles and polymeric nanoparticles. Novel formulation avenues, including solidified self-emulsifying systems, supersaturated self-emulsifying systems, solid-lipid nanoparticles, and nanostructured lipid-carriers, are also explored. Systematic in vitro and in vivo investigations of these formulations can provide essential in vitro-in-vivo correlation insights. Integration of lipid formulation-specific parameters into a physiologically based pharmacokinetics model can facilitate improved clinical translation of lipid-based VTX formulations. ARTICLE HIGHLIGHTS: Venetoclax can benefit from reformulation using novel bio-enabling strategies for enhanced oral absorption Rational formulation design can beneficially affect the performance of bio-enabling systems Use of advanced lipid-based formulations and/or inorganic vehicles, can enhance pharmacokinetics and reduce limitations of the current clinical use of venetoclax Combining advanced formulation science and modelling is key for clinical success of venetoclax-based lipid formulations.
Clinical translation and landscape of copper nanoparticles.
Hadiwinata RD, Zhang R, Barmin RA … +3 more , Kiessling F, Lammers T, Pallares RM
Drug Deliv Transl Res · 2026 Mar · PMID 41795057 · Publisher ↗
Although the medical use of copper dates back millennia and medicines based on copper nanoparticles have been employed for over a century, their benefits are still often questioned. Over the past three decades, advances...
Although the medical use of copper dates back millennia and medicines based on copper nanoparticles have been employed for over a century, their benefits are still often questioned. Over the past three decades, advances in nanotechnology have renewed interest in copper-based nanoformulations for healthcare. While most preclinical studies have focused on systemically administered copper nanomedicines for a broad range of therapeutic purposes, clinical trials remain scarce and are primarily centered on topical applications, where long-term off-target accumulation can be minimized to mitigate safety concerns. Despite exhibiting only moderate antiseptic activity compared with other inorganic nanomaterials, copper nanoparticles demonstrate significant wound healing potential through complex mechanisms involving angiogenesis promotion and stabilization of extracellular skin proteins. In this work, we discuss the current landscape of copper nanoparticles (and related microparticulate structures), and we thoroughly analyze the characteristics that have enabled their translation and use in clinical settings.
A multi-compartment pulsatile drug delivery system for sequential release: in vitro and in vivo evaluation.
Yoo SD, An Y, Kim G … +2 more , Shin BS, Shin S
Drug Deliv Transl Res · 2026 Mar · PMID 41774404 · Publisher ↗
This study presents an innovative, structurally engineered, pulsatile oral drug delivery platform that enables programmable, sequential drug release by integrating a structurally engineered three-dimensional (3D)-printed...
This study presents an innovative, structurally engineered, pulsatile oral drug delivery platform that enables programmable, sequential drug release by integrating a structurally engineered three-dimensional (3D)-printed capsular device with conventional immediate-release (IR) tablets. Unlike coating-based or multilayer systems, which suffer from complex manufacturing and inconsistent release profiles, the multi-compartment capsule provides precise and reproducible control over the release timing through simple structural modifications. Each compartment accommodated intact IR tablets, allowing immediate release from the open-window sections and delayed release from the barrier-enclosed compartments. The lag time (T) before drug release can be predictably tuned by adjusting the barrier wall thickness. The system was optimized for esomeprazole and naproxen, for which gastroprotection requires temporally separated exposure. The in vitro dissolution displayed immediate release of esomeprazole and delayed release of naproxen with T of 11.33 ± 1.37 h. Both immediate absorption of esomeprazole and delayed absorption of naproxen were observed following oral administration in beagle dogs. The time to maximum plasma concentration (T) of esomeprazole was 0.67 ± 0.67 h, whereas the T of naproxen was 9.83 ± 2.40 h with a T of 4.75 ± 1.17 h. These findings demonstrate that this modular 3D-printed platform, combined with conventional tablets, provides controlled and sequential drug delivery, thereby supporting patient-tailored therapeutic regimens.
Nano-antimicrobial peptides (Nano-AMPs) to combat resistant gram-negative bacteria.
Saleem N, Kumar N, El-Omar E … +2 more , Willcox M, Jiang XT
Drug Deliv Transl Res · 2026 Mar · PMID 41772350 · Publisher ↗
The emergence of antimicrobial resistance (AMR) poses a critical threat to public health worldwide, making conventional antibiotics ineffective against multidrug-resistant (MDR) pathogens. This literature review examines...
The emergence of antimicrobial resistance (AMR) poses a critical threat to public health worldwide, making conventional antibiotics ineffective against multidrug-resistant (MDR) pathogens. This literature review examines the potential therapeutic applications of nano-antimicrobial peptides (Nano-AMPs), with a focus on multidrug-resistant pathogens prioritized by the World Health Organisation (WHO). Antimicrobial peptides (AMPs) are essential components of the innate immune system with broad-spectrum bactericidal and immunomodulatory properties, and have emerged as promising alternatives to conventional antibiotics because of their unique mechanisms of action (e.g., membrane disruption, pore formation, and immunomodulation). Currently, the clinical translation of AMPs is hindered by several challenges, including enzymatic and non-enzymatic degradation, poor bioavailability, and biocompatibility issues, as well as local and systemic adverse events. To address these concerns, recent advancements in nanocarrier delivery systems offer novel solutions, enabling selected and targeted drug delivery, enhanced bioavailability, and controlled and sustained AMP release. Lipid-based nanocarriers (e.g., liposomes), polymeric and other nanocarrier systems improve peptide solubility and limit off-target events, while inorganic carriers like gold, silver, and silica nanoparticles facilitate functionalization and synergism to combat MDR Gram-negative infections. Despite promising findings, challenges such as production, long-term efficacy and safety, and regulatory approval persist. Therefore, interdisciplinary efforts, such as advanced machine learning methods alongside conventional pharmacological approaches, may be needed to optimize nanocarrier designs and validate clinical efficacy and safety in preclinical and clinical trials. This review critically analyses the latest evidence on different nanocarriers and their synergistic effects, highlighting their transformative potential to combat AMR, thereby offering insights to develop next-generation antibiotics, particularly against Gram-negative pathogens.
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