Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
Assessment of AAV/polyketal chimeric nanoparticles for ocular gene transduction using an animal model.
Castro BFM, Lugin M, Guerra MCA … +5 more , Dias MF, Lee RT, Silva-Cunha A, Kwon YJ, Fialho SL
Drug Deliv Transl Res · 2026 Apr · PMID 41120778 · Publisher ↗
Gene therapy has made significant progress in ophthalmology in recent years, particularly through adeno-associated virus (AAV)-mediated delivery. Despite well-known advantages of AAV vectors, their restricted cargo capac...
Gene therapy has made significant progress in ophthalmology in recent years, particularly through adeno-associated virus (AAV)-mediated delivery. Despite well-known advantages of AAV vectors, their restricted cargo capacity, immunogenicity, and the presence of neutralizing antibodies against commonly used serotypes limit their use and efficacy. To address these limitations, we developed viral/nonviral chimeric nanoparticles (ChNPs) consisting of AAV2 vectors encapsulated by a polyketal acid-degradable polymeric shell and further functionalized with hyaluronic acid (HA). Additionally, a scrambled siRNA was incorporated into the polymeric shell to enable a multimodal therapeutic approach. In vitro safety, transduction efficiency and siRNA internalization of ChNPSs was investigated in retinal cells followed by an in vivo safety assessment for intravitreal delivery in rats. Characterization of ChNPs confirmed successful functionalization with HA, which resulted in improved size and uniformity as well as enhanced transduction efficiency in retinal cells when compared to HA-free ChNPs. Moreover, HA coating improved biocompatibility by maintaining retinal cells' viability when incubated with ChNPs and allowed efficient siRNA internalization. A comprehensive in vivo assessment demonstrated that both HA-conjugated and HA-free ChNPs preserved retinal function, integrity, and morphology. Furthermore, the intraocular pressure and retinal thickness was not affected by ChNPs, confirming their safety for intravitreal delivery. Therefore, ChNPs coated with HA represent a promising alternative to overcome challenges with the most widely employed AAV vector in ocular gene delivery. Our findings support the potential for intravitreal administration of ChNPs and in multimodal gene expression/silencing strategies.
Ex vivo validation of osteogenic efficacy in a bioceramic dual drug-delivery system.
Rodrigues MA, Grenho L, Araújo R … +5 more , Borges JP, Fernandes MH, Gomes PS, Santos JD, Lopes MA
Drug Deliv Transl Res · 2026 Jun · PMID 41118110 · Publisher ↗
Alendronate (ALN) is widely employed against skeletal disorders, but its low oral bioavailability and prolonged skeletal retention necessitate high systemic doses that carry significant risk. The research team previously...
Alendronate (ALN) is widely employed against skeletal disorders, but its low oral bioavailability and prolonged skeletal retention necessitate high systemic doses that carry significant risk. The research team previously developed a novel bioceramic drug-delivery system (DDS) that sequentially releases gentamicin during the first two weeks post-implantation (with reported therapeutic concentrations released daily) and ALN thereafter to be used as a bone substitute. The main objective of this study was to validate the DDS's osteogenic capacity ex vivo, once gentamicin had been depleted and only ALN was released.Before ex vivo testing, there was a need to confirm, via in vitro biological assessment, if the release profile of ALN achieved the therapeutic values needed. For that purpose, human bone-marrow stromal cells (hBMSCs) were exposed to ALN concentrations between 10⁻⁴ and 10⁻¹¹ M for 20 days. Concentrations from 10⁻⁶ to 10⁻¹⁰ M enhanced metabolic activity, alkaline-phosphatase activity, matrix mineralisation (Alizarin Red, von Kossa), and early- to mid-stage osteogenic gene expression (RUNX2, SP7, COL1A1, ALP, BMP-2), while late marker BGLAP remained suppressed, indicating ongoing differentiation. Having confirmed that the ALN release profile of the DDS met the therapeutic need, the DDS was then validated, as an osteogenic bone substitute system, in the ex vivo model.For validation of the DDS, embryonic chick femurs were cultured ex vivo for 11 days with DDS preconditioned by release assay at day 17-representing the alendronate release phase, only. Treated femurs exhibited a significant increase in bone volume fraction, accompanied by enhanced deposition of a collagen-rich extracellular matrix and a more highly organized trabecular network, while total femoral volume remained constant. Histological staining and polarized-light microscopy further revealed that the extracellular matrix in the sample group was denser, more mature and organized than in controls.These findings verify that the sequential DDS releases ALN at osteogenically effective concentrations precisely when antibiotic coverage ends, affirming its capacity to couple early infection control with subsequent, localised stimulation of bone formation while avoiding systemic exposure.
Correction: Toward a harmonized regulatory framework for 3D-printed pharmaceutical products: the role of critical feedstock materials and process parameters.
Alzhrani R, Fitaihi RA, Majrashi MA … +2 more , Zhang Y, Maniruzzaman M
Drug Deliv Transl Res · 2025 Dec · PMID 41116067 · Full text
Abstract loading — click title to view on PubMed.
Strategic lipid nanoparticle design dictates retinal delivery post inner limiting membrane disruption.
De Clerck K, De Coster E, Paoletti L … +3 more , De Smedt S, Remaut K, Peynshaert K
Drug Deliv Transl Res · 2026 Jun · PMID 41116066 · Publisher ↗
The interest in lipid nanoparticle (LNP)-mediated mRNA delivery significantly accelerated in the aftermath of the clinical success of mRNA-based COVID-19 vaccines. Validated as an effective and scalable platform, LNPs ar...
The interest in lipid nanoparticle (LNP)-mediated mRNA delivery significantly accelerated in the aftermath of the clinical success of mRNA-based COVID-19 vaccines. Validated as an effective and scalable platform, LNPs are now considered a cornerstone technology for the development of next-generation nucleic acid therapeutics. Recently, mRNA therapy entered the field of retinal gene therapy where it could treat retinal disorders contributing to the global numbers of vision impairment and blindness. While an historically driven focus on targeting outer retinal cells was initially in place, a shift toward delivery to the inner retina via intravitreal injection is ongoing. Yet, successful delivery is cumbersome since many nanocarriers are trapped at the inner limiting membrane (ILM). Therefore, this study enlightens the role of the ILM barrier with due consideration how fine-tuning LNP design impacts delivery after ILM disruption. For a standard LNP composition, we showed that ILM disruption is resulting in remarkable amounts of mRNA expression as opposed to an intact ILM. Based on an in-depth in vitro screening, the standard DSPC helper lipid was switched to DOPE to enhance expression levels and the percentage of PEGylation was adjusted to define LNP size. Despite the negative impact of elevated PEGylation on transfection efficiency in vitro, a significant boost in transfected retinal cells was noticed in an ex vivo setting due to improved penetration in the retina. In conclusion, we demonstrated that strategic design of LNP composition can boost LNP delivery beyond the ILM barrier and drive mRNA-LNP therapy to the retina forward.
Localized co-delivery of in-situ hydrogel containing ibrutinib-PLGA-PEG-folate nanoparticle and octreotide microsphere to glioblastoma.
Morshedi B, Esfandyari-Manesh M, Ghahremani MH … +2 more , Fatahi Y, Dinarvand R
Drug Deliv Transl Res · 2026 Jun · PMID 41116065 · Publisher ↗
Glioblastoma (GBM), a grade IV astrocytoma, is defined by its rapid proliferation, strong infiltrative nature, resistance to chemotherapy, and tendency to recur quickly, even after surgery and standard treatments. We hyp...
Glioblastoma (GBM), a grade IV astrocytoma, is defined by its rapid proliferation, strong infiltrative nature, resistance to chemotherapy, and tendency to recur quickly, even after surgery and standard treatments. We hypothesize that the localized delivery of ibrutinib loaded in PLGA-PEG-folate nanoparticles (IBT-PPF-NPs) and Octreotide PLGA microparticles (OCT-PLGA-MPs) loaded GelMA hydrogel into GBM tumors represents a promising approach, as it can achieve a high local drug concentration in the tumor site and increase the efficacy of treatment.The OCT-PLGA-MPs were prepared and incorporated with IBT-PPF-NPs in GelMA-alginate hydrogel. The in-situ hydrogel was developed using GelMA combined with different alginate concentrations, and its swelling behavior, degradation rate, and mechanical and morphological characteristics were investigated. The efficiency of Octreotide entrapment in PLGA microparticle was 55.0% ± 0.7 with 5.0% ± 0.03 drug loading. The particle size of the OCT-PLGA-MPs was 103 μm ± 5.6. Octreotide exhibited a gradual release profile from the microparticles (MPs), with approximately 5.2% released within the first 24 h and up to 71% released over 84 days. The embedding of OCT-PLGA-MPs within the hydrogel and IBT-PPF-NPs effectively controls the initial burst release typically observed with NPs and MPs. The structure of the GelMA was verified through 1H NMR analysis. The selected hydrogel demonstrated an elastic modulus of 18.45 kPa, consistent with the mechanical properties of brain tissue. MTT assay results revealed that IBT-PPF-NPs inhibit the growth of glioma cells in a dose-dependent manner, while Octreotide alone exhibited no cytotoxic effect on glioma cells. The MTT results also indicate an additive effect between the combination of the two treatments. An in vivo study was performed to evaluate the effectiveness of intratumoral injection of hydrogel in inhibiting tumor growth by MRI imaging. Then the collected brain tumors were evaluated by H&E and IHC staining analysis. The hydrogel containing IBT-PPF-NPs and OCT-PLGA-MPs effectively suppressed tumor growth in the in vivo study. The IHC results revealed a significant increase in caspase-3 levels and a decrease in the Ki-67 marker in glioma tumor cells by ibrutinib. On the other hand, Octreotide notably reduced CD31 expression, inhibiting angiogenesis and effectively suppressing both tumor growth and glioma cell proliferation in the in vivo study. It holds potential as a valuable approach for post-resection management of GBM, preceding standard chemo-radiation therapy.
Preliminary study on targeted therapy of breast cancer using tumor cell membrane-coated dual-loaded liposomes based on chemo-photothermal synergistic effects.
Wang Y, Pang S, Lu Y … +4 more , Guo X, Li C, Chen M, Ren X
Drug Deliv Transl Res · 2026 Jun · PMID 41116064 · Publisher ↗
Addressing the clinical challenges of lacking effective therapeutic targets and the high recurrence rate in triple-negative breast cancer (TNBC), this study innovatively constructed a targeted nanoplatform (CM@DOX-GO NPs...
Addressing the clinical challenges of lacking effective therapeutic targets and the high recurrence rate in triple-negative breast cancer (TNBC), this study innovatively constructed a targeted nanoplatform (CM@DOX-GO NPs) based on the synergistic combination of photothermal therapy (PTT) and chemotherapy. This platform achieves a breakthrough integration of spatiotemporally coordinated PTT-chemotherapy and precise targeting by co-loading the highly efficient photothermal agent, monolayer graphene oxide (GO), and the chemotherapeutic drug doxorubicin hydrochloride (DOX) into core-shell structured liposomes, followed by biomimetic modification with tumor cell membranes (derived from MDA-MB-231 cells). Serving as a novel near-infrared (NIR) photosensitizer, GO exhibits a unique photothermal effect that not only directly induces tumor cell death but also enhances cellular membrane permeability through hyperthermia, thereby promoting the intertumoral penetration and targeted release of DOX. Experimental results confirmed that the tumor cell membrane-camouflaged nanoparticles exhibit significantly enhanced homologous targeting capability compared to conventional formulations. Their optimized systemic circulation characteristics and specific fluorescence enrichment within the tumor region collectively validate the effectiveness of the biomimetic strategy. Under NIR irradiation, this system leverages the spatiotemporally coordinated mechanism of PTT-chemotherapy, substantially improving tumor cell eradication efficiency while simultaneously reducing systemic toxicity through precise energy control. This innovative design successfully overcomes the limitations inherent in conventional PTT, such as uneven energy distribution and low bioavailability of photosensitizers, offering a promising new strategy for highly efficient and low-toxicity TNBC treatment.
Rapid dissolving microneedle patch integrated with benidipine-loaded nanotransfersomes for transdermal drug delivery: optimization, characterizations, and preclinical bioavailability assessment.
Al-Japairai K, Almurisi SH, Alheibshy F … +2 more , Abdul-Halim N, Mahmood S
Drug Deliv Transl Res · 2026 May · PMID 41094229 · Full text
Benidipine hydrochloride (BEN) is widely prescribed for managing hypertension; however, its clinical efficacy is limited by poor oral bioavailability. This study introduces an innovative delivery approach, incorporating...
Benidipine hydrochloride (BEN) is widely prescribed for managing hypertension; however, its clinical efficacy is limited by poor oral bioavailability. This study introduces an innovative delivery approach, incorporating BEN-loaded nanotransfersomes (BEN-TF) into a rapid dissolving microneedles (DMNs) patch for transdermal administration. The nanotransfersomal formulation was optimised via a Box-Behnken design following preparation using a thin-film hydration method. The optimised formulation exhibited favourable characteristics, including a vesicle size of 124.9 ± 1.49 nm, high entrapment efficiency (98.12 ± 0.18%), and transdermal flux of 9.74 ± 0.53 μg/cm/hr. DSC, ATR-FTIR, and XRD analyses confirmed the amorphous state of BEN. Imaging via FESEM and HRTEM demonstrated spherical, uniform nanosized vesicles. Confocal microscopy revealed deep skin penetration. The integration of BEN-TF into DMNs (BEN-TF-DMNs) resulted in efficient skin insertion, rapid dissolution, and good mechanical strength. Ex-vivo results indicated superior permeation compared to BEN-TF or BEN-DMNs alone, while the in-vivo study confirmed improved bioavailability versus both oral tablets and BEN-DMNs. This hybrid delivery platform offers a promising strategy for improving the systemic delivery of BEN.
Electron paramagnetic resonance (EPR) meets drug delivery and biomaterials: a magnetic love story.
Gallez B
Drug Deliv Transl Res · 2026 Jul · PMID 41094228 · Full text
This narrative review underscores the powerful role of Electron Paramagnetic Resonance (EPR), also known as Electron Spin Resonance (ESR), in characterizing drug delivery systems (DDSs). Using drugs or probes tagged with...
This narrative review underscores the powerful role of Electron Paramagnetic Resonance (EPR), also known as Electron Spin Resonance (ESR), in characterizing drug delivery systems (DDSs). Using drugs or probes tagged with spin labels, EPR provides detailed insights into structural and dynamic properties, as well as the molecular microenvironment (including micro-viscosity, micro-polarity, and micro-pH) and enables real-time monitoring of drug release and degradation processes both in vitro and in vivo. In nanomedicine research, EPR can also serve as a quantitative tool to track the fate of DDSs doped with iron oxide particles that are used in theranostics. Beyond DDS characterization, EPR has contributed substantially to elucidating radical mechanisms within material matrices, notably in bone cements and dental resins used for restorative applications. Moreover, incorporating paramagnetic compounds into DDSs or biomaterials has broadened the scope of EPR applications, enabling precise measurements of oxygen and nitric oxide levels in complex biological environments. The incorporation of oxygen sensors into biocompatible matrices has also enabled the development of implantable resonators for measuring oxygen at substantial tissue depths. Incorporating oxygen sensors into cell therapy implantable devices or grafted tissues can serve as an indicator of both oxygenation and vascularization.
Engineering a nifurtimox nanosuspension: toward improved pharmaceutical attributes.
Magi MS, Lopez-Vidal L, García MC … +2 more , Palma SD, Jimenez-Kairuz AF
Drug Deliv Transl Res · 2026 Jun · PMID 41083754 · Publisher ↗
Nifurtimox (NFX) is one of the two approved drugs for the treatment of Chagas disease, a neglected parasitic infection caused by Trypanosoma cruzi. Classified as a biopharmaceutics classification system class II/IV drug,...
Nifurtimox (NFX) is one of the two approved drugs for the treatment of Chagas disease, a neglected parasitic infection caused by Trypanosoma cruzi. Classified as a biopharmaceutics classification system class II/IV drug, NFX exhibits poor aqueous solubility, which significantly limits its dissolution rate and results in erratic bioavailability. This study aimed to develop and characterize a novel nanosuspension of NFX (NFX-NS), composed of drug nanocrystals (NFX-NCs), as a strategy to enhance drug solubility and dissolution, while also enabling administration to pediatric patients. NFX-NS was prepared using a top-down, organic solvent-free wet milling approach, followed by lyophilization to obtain the solid-state formulation. A physicochemical characterization, solubility testing of NFX-NCs, and dissolution studies of NFX-NS were conducted, alongside in vitro biological evaluation. The resulting NFX-NS exhibited a particle size of approximately 200 nm, with a polydispersity index below 0.2 and demonstrated stability for at least 120 days. NFX retained its crystalline structure post-processing, with no significant changes in its physicochemical properties, indicating minimal interaction with the stabilizer. The aqueous solubility of NFX-NCs was enhanced tenfold compared to that of the raw drug, and a substantial improvement in the dissolution rate was observed. In vitro assays revealed significantly increased anti-T. cruzi activity for NFX-NCs, along with improved biocompatibility in human endothelial cells. These findings highlight the potential of NFX-NS as the first NCs-based formulation of NFX, offering a promising therapeutic alternative for pediatric use and addressing the solubility-related challenges associated with the drug.
Nanoemulsion as a promising drug delivery strategy for effective eradication of Helicobacter pylori: current insights.
Saha M, Gupta A, Kunkalienkar S … +8 more , Dhas N, Shetty S, Gupta A, Mutalik S, Krishnadas N, Chandrashekar R, Narasimhaswamy N, Moorkoth S
Drug Deliv Transl Res · 2026 Jan · PMID 41083753 · Full text
Helicobacter pylori (H. pylori) have infected about 50% of the world's population and is a leading cause of gastrointestinal diseases, including gastritis, peptic ulcer, and stomach cancer. Current treatment regimens oft...
Helicobacter pylori (H. pylori) have infected about 50% of the world's population and is a leading cause of gastrointestinal diseases, including gastritis, peptic ulcer, and stomach cancer. Current treatment regimens often fail to completely eradicate the bacteria due to the failure of antibiotics to penetrate into stomach's inner mucosa, where the bacteria reside. Additional factors such as the ability of the organism to neutralize the stomach's acidic environment and biofilm formation further contribute to treatment failure leading to antibiotic resistance. These challenges underscore the urgent need for new treatment options and strategies to combat H. pylori effectively. The current review delivers an overview of the pathophysiology of H. pylori, the limitations of the current regimens, and the potential of nanoemulsion as a smart carrier addressing the limitations associated with H. pylori treatment. The nanoemulsion offers specific advantages like mucoadhesion potential, targeted delivery, controlled release, and co-delivery options that ultimately results in an enhancement of bioavailability of the antibiotics to H. pylori, which resides in the inner walls of the stomach mucosa. Further, the ability of nanoemulsions to encapsulate the drug molecules helps in protecting the antibiotics from the stomach acidity facilitating drug stability. In conclusion, the review highlights the importance of tapping this unexplored potential of nanoemulsion as a promising drug delivery option for the treatment of H. pylori infection.
From simulation to application: enhancing preclinical evaluation of dissolvable microarray patches through PBPK modelling.
Railic M, de Witte WEA, Schaller S … +6 more , Agboola ST, Sartawi Z, Faisal W, Elkhashab M, Crean A, Vucen S
Drug Deliv Transl Res · 2026 May · PMID 41073847 · Full text
Dissolvable microarray patches (MAP) represent a promising drug delivery platform; however, the absence of standardised protocols for their preclinical evaluation poses a significant barrier to regulatory approval and cl...
Dissolvable microarray patches (MAP) represent a promising drug delivery platform; however, the absence of standardised protocols for their preclinical evaluation poses a significant barrier to regulatory approval and clinical translation. Physiologically Based Pharmacokinetic (PBPK) modelling is a powerful tool for predicting drug kinetics following MAP application, addressing key challenges associated with in vitro and in vivo studies such as experimental variability, complex study design, and data extrapolating across different populations. However, adapting PBPK models for dissolvable MAP is inherently complex due to the interplay between microneedle geometry, drug release kinetics, and skin physiology. In this study, an existing dermal PBPK model in MoBi was optimised for dissolvable MAP by incorporating microneedle geometry and in vitro release profiles of MAP formulations containing the antihistamines loratadine (LOR) and chlorpheniramine maleate (CPM), as well as the antifungal drug itraconazole (ITZ). Model refinement involved systematically optimising input parameters related to skin thickness and drug-skin diffusion, partitioning and binding, to enhance predictive accuracy. Validation was performed using in vitro permeation testing with porcine skin for CPM and LOR MAP, alongside in vivo preclinical studies in pigs for ITZ MAP. The optimised model demonstrated robust predictive performance across the diverse drug molecules and experimental conditions investigated, highlighting its value as a powerful tool to accelerate preclinical MAP development.
Synergistic effect of Aloe Vera hydrogels with imatinib for pH-responsive drug release in breast cancer treatment.
Khan AH, Shehzad A, Pirela P … +6 more , Atalaia M, Ruivinho B, Rashan L, Miran W, Duarte SOD, Fonte P
Drug Deliv Transl Res · 2026 Jun · PMID 41065988 · Publisher ↗
Imatinib (IM) efficacy as a cancer drug is limited by pharmacokinetic drug resistance developed during systemic circulation before reaching the target site.Hydrogels have attracted attention because of their characterist...
Imatinib (IM) efficacy as a cancer drug is limited by pharmacokinetic drug resistance developed during systemic circulation before reaching the target site.Hydrogels have attracted attention because of their characteristic physiochemical and biochemical properties, flexibility, and the ability to release drugs directly at target sites causing cancer mitigation. The current study aims at developing Aloe Vera (AV) hydrogels for the efficient and targeted delivery of IM into cancer cells and studying its synergistic effect. Incorporating Aloe Vera into the previously studied Sodium Alginate (SA)/PolyVinyl Alcohol (PVA) hydrogels and loading with IM is expected to reach a pH-responsive release efficiency, enhanced biochemical properties and increased cancer cell cytotoxicity. The hydrogels, SA/PVA and SA/PVA/AV were characterized (FT-IR, SEM) and investigated for their physiochemical properties. The presence of AV and IM were confirmed by the increase in the intensity of band from 3000 to 3500 cm, while an increase in the pore size was observed upon the loading of IM. The final formulation, SA/PVA/AV hydrogels displayed increased pore size which leveraged their swelling, degradation, encapsulation, and release properties by 400%, 100%, 56%, and 94%, respectively. The in vitro analysis on breast cancer cells showed that the SA/PVA/AV hydrogels loaded with IM worked synergistically to significantly reduce the cancer cell viability to 40%, surpassing the efficacy of the SA/PVA/AV hydrogel and IM treatments alone. This study highlights the promising potential for the use of AV in the development of a drug delivery system (DDS) for targeting and improving therapeutic outcomes in cancer treatment.
Exploring the impact of various zwitterionic surface modifications on the mucus diffusion and membrane permeability of lipid-based nanocarriers.
Spennacchio A, Richter LM, Stengel D … +5 more , Hermann M, Lopedota AA, Lopalco A, Denora N, Bernkop-Schnürch A
Drug Deliv Transl Res · 2026 Jun · PMID 41065987 · Full text
This study investigates the effect of structural differences among six zwitterionic surfactants on the performance of lipid-based nanoemulsions. Nanoemulsions were prepared using a standardized formulation approach to mi...
This study investigates the effect of structural differences among six zwitterionic surfactants on the performance of lipid-based nanoemulsions. Nanoemulsions were prepared using a standardized formulation approach to minimize compositional variability, thereby isolating the influence of surfactant type. The headgroups of the zwitterionic surfactants, phosphorylcholine, carnitine, amine oxide, betaine, and sulfobetaine, were evaluated for their impact on key parameters including physical stability, cytotoxicity, mucus diffusion, and cellular uptake within the overall surfactant structure. Results revealed significant variations in nanoemulsion performance depending on the zwitterionic surfactant structure. Formulations containing the surfactant cocamidopropyl hydroxysultaine exhibited moderate cytotoxicity but demonstrated superior diffusion through porcine mucus and enhanced uptake by human cells. In contrast, n-dodecylphosphocholine-based nanoemulsions showed excellent stability across all tested biorelevant media coupled with low cytotoxicity. Lipid-based nanocarriers formulated with lauryldimethylamine oxide combined good stability in biorelevant media with high mucus diffusion and moderate cellular uptake. Lauryl betaine-based systems displayed low hemolytic and moderate cytotoxic activities, but showed limited mucus penetration and cellular uptake. This study elucidates critical differences among various zwitterionic surfactants and highlights their suitability for liquid pharmaceutical formulations in the nanoscale range.
Photothermal and pH-stimuli-responsive mesoporous silica nanoparticles drug delivery system for targeting the tumor cells.
Chen Q, Wu Z, Ji Y … +7 more , Zheng X, Liu C, Zhou C, Shan X, Sheng J, Ren Q, Wei K
Drug Deliv Transl Res · 2026 May · PMID 41065986 · Publisher ↗
To improve the precision of cancer therapy, multi-stimuli responsiveness and targeted, controllable drug release are essential components. In this study, we designed an intelligent drug delivery system that integrates ch...
To improve the precision of cancer therapy, multi-stimuli responsiveness and targeted, controllable drug release are essential components. In this study, we designed an intelligent drug delivery system that integrates chemotherapy and photothermal therapy with pH- and photothermal-sensitive controlled drug release capabilities. This system encapsulates CuS nanoparticles and a model drug Metformin (Met) within Mesoporous Silica Nanoparticles (MSN), which are subsequently coated with a thin layer of Polydopamine (PDA) to enhance multiple photothermal conversion functions. Met, widely recognized for its role in treating type 2 diabetes, has been shown to possess anti-tumor properties. Consequently, it was chosen as the model drug encapsulated within the mesoporous silica nanoparticles. Our investigation about the drug release behavior demonstrated that the PDA coating on MSN not only mitigates the initial burst release of metformin but also facilitates sustained, pH- and thermally-responsive release at pH 6.5, achieving a cumulative release of 67.1% by the tenth day. Furthermore, the PDA modification significantly improves the photothermal conversion performance and stability of CuS@MSN. The photothermal conversion efficiency (PCE) of CuS@MSN and CuS@MSN@PDA (CMP) were measured at 42.7% and 59.9%, respectively. Additionally, on the 28th day post-tumor resection, the met@CMP group exhibited an 80% lower tumor recurrence rate compared to the met group alone. This research highlights the substantial potential of intelligent CMP nanoparticles for multi-stimuli responsive, precise chemo-photothermal synergistic therapy in cancer treatment.
Impact of sodium caprate dosed as a mini-tablet or suspension on insulin delivery and mucosa histomorphology.
Fredholt F, Heade J, Rantanen J … +2 more , Rønholt S, Nielsen HM
Drug Deliv Transl Res · 2026 Jun · PMID 41062878 · Full text
Oral administration of solid dosage forms for delivery of therapeutic peptides is highly desired. Preclinical investigations on co-administration with permeation enhancers (PEs) to enable sufficient oral bioavailabilitie...
Oral administration of solid dosage forms for delivery of therapeutic peptides is highly desired. Preclinical investigations on co-administration with permeation enhancers (PEs) to enable sufficient oral bioavailabilities are, however, predominantly done using liquid formulations despite the commercial end-goal being a solid dosage form. Given the amounts needed of PE, this will typically result in a compacted tablet with high amounts of the PE of choice. The aim of this study was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of insulin after co-formulation with a fixed dose of sodium caprate (C10) in solid dosage forms versus liquid dosage forms. PK/PD parameters in rats were evaluated after dosing mini-tablets and liquid formulations with different amounts of insulin and 26 mg/kg C10 after intestinal administration. Absorption of insulin was dose-dependent in the presence of the PE for both types of dosage forms, which was also reflected in the blood glucose levels. A significant absorption enhancing effect of C10 was found when dosing a 75 IU/kg insulin mini-tablet, resulting in a 26-fold increase in bioavailability. The effect of C10 on the rat intestinal tissue was investigated by histomorphological assessment evaluating erosion and villi height. Effects caused by the C10 mini-tablets and the liquid formulations were similar and shown to be transient. Overall, the findings in this study suggest that mini-tablets can be used to assess peptide bioavailability and the effect of PEs in rats as a preclinical model, and PK data may be nominally different from those obtained with liquid formulations.
A virtual factory for topical formulations based on molecular modeling and drug-polymer interaction studies.
Modh H, Benetti AA, Badruddoza AZ … +5 more , Yan J, Panczyk T, Shah J, Pastorin G, Wacker MG
Drug Deliv Transl Res · 2026 Jun · PMID 41044466 · Publisher ↗
Topical drug delivery offers a cost-effective and non-invasive alternative to systemic drug administration but faces challenges due to the skin's barrier properties and the complex rheology of semisolid formulations. Thi...
Topical drug delivery offers a cost-effective and non-invasive alternative to systemic drug administration but faces challenges due to the skin's barrier properties and the complex rheology of semisolid formulations. This necessitates a deeper understanding of the interplay between formulation components and their impact on drug release and therapeutic efficacy. Emulsifying two-component polymer system, supplied as ready-to-use liquid dispersions of oil and surfactant, is increasingly used to simplify manufacturing processes. However, their interaction with active pharmaceutical ingredients (APIs) can unpredictably alter formulation properties. This study investigates how the model APIs (bupivacaine, lidocaine, and atenolol) influence key formulation properties, such as rheology, drug release, and manufacturing efficiency. A systematic, dose-dependent reduction in viscosity was observed with increasing API concentration, an effect attributed to the disruption of the polymer network via electrostatic interactions. This effect remained consistent across different amine classes and was successfully fitted using an exponential function. While formulation pH did not significantly affect viscosity, lower pH values accelerated drug release, highlighting the interplay between gel microstructure, drug-polymer interactions, and release kinetics within this polymer system. Molecular modeling revealed preferential localization of ionized APIs at the polymer-oil interface, while unionized APIs adsorbed onto the oil surface. Detachment force simulations further quantified these interactions. Ex-vivo skin permeation studies confirmed the influence of viscosity on drug permeation, with lower viscosity gels exhibiting faster permeation rates. Finally, in a novel molecule-to-manufacturing approach, these multi-scale insights were integrated into a "Virtual Factory" model. This model successfully predicted the impact of API concentration on manufacturing parameters, offering a valuable tool to optimize equipment selection, process parameters, and energy consumption. This work provides a comprehensive framework for the rational design of topical systems, connecting molecular interactions to final manufacturing outcomes.
Advanced lipid-based niosomes for enhanced transdermal delivery of olmesartan medoxomil via intracutaneous drug depot: a novel biomimicry approach.
Fouad SA, Gebril MI, Abd Allah FI … +4 more , Teaima MH, El-Nabarawi M, Elmowafy M, Sarhan OM
Drug Deliv Transl Res · 2026 Jun · PMID 41032162 · Publisher ↗
Olmesartan medoxomil (OMN), a highly selective antihypertensive agent but, with problematic oral delivery due to its low solubility and limited bioavailability. Therefore, biomimetic lipid-based niosomes were adopted as...
Olmesartan medoxomil (OMN), a highly selective antihypertensive agent but, with problematic oral delivery due to its low solubility and limited bioavailability. Therefore, biomimetic lipid-based niosomes were adopted as a novel approach to enhance OMN solubility and boost its transdermal delivery (TD). Initially, conventional niosomes were prepared by thin film hydration method. Formulation parameters were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 300 nm), zeta potential (ZP > ± 25 mV), and polydispersity index (PDI < 0.5). Based on these parameters, OMN-Ns-3 was selected for further modulation. Concomitantly, screening studies of OMN in 9 liquid lipids; clove oil, Maisine CC, Transcutol HP, castor oil, olive oil, Miglyol 812, soybean oil, sesame oil, and cottonseed oil were performed. Among them, the first three showed the highest solubility of OMN; ~16.30 ± 1.80, 25.60 ± 2.20, and 38.35 ± 1.30 mg/mL, respectively. Hence, they were incorporated into OMN-Ns-3 to obtain the modulated niosomal formulation; M/C-OMN-Ns-T. It showed accepted EE 98.70 ± 1.40%, PS 186.30 ± 2.40 nm, ZP -36.20 ± 0.70 mV, and PDI 0.34 ± 0.03. It showed enhanced cumulative amount of OMN permeated; Q 93.72 ± 0.49%, Q 97.56 ± 0.66%, and Q 98.22 ± 1.15%. Ex vivo studies showed significantly enhanced flux (J) compared to conventional niosomes with enhancement ratio values ~ 1.6 at 24/48 h, and 1.5 at 72 h (p < 0.0001). Confocal Laser Scanning Microscopy showed vast distribution and deep localization of fluorescent M/C-OMN-Ns-T, creating in-skin depot for sustained OMN diffusion to the systemic circulation. TEM images showed nanosized, non-aggregated spherical vesicles. Physical stability studies showed no significant changes in EE, PS, ZP, and PDI. M/C-OMN-Ns-T formulated into transdermal patch (TP) showed accepted physicochemical properties including; thickness, folding endurance, surface pH, drug content Q, and Q. In vivo pharmacokinetic studies of TP showed significantly enhanced relative bioavailability ~ 674.04% compared to angiosartan oral tablets (p < 0.0001). It could be concluded that TD of M/C-OMN-Ns-T reflected its superiority over conventional lipid-free niosomes. Our study introduced the potential of liquid lipids as biomimetic fluidizing agents for enhanced TD of conventional nanocarriers. The developed TP could be a competent alternative to conventional oral delivery of OMN.
Publisher Correction: Inhaled biologics for respiratory diseases: clinical potential and emerging technologies.
Shaibie NA, Mohammad Faizal NDF, Buang F … +2 more , Srichana T, Mohd Amin MCI
Drug Deliv Transl Res · 2026 Jan · PMID 41015633 · Full text
Abstract loading — click title to view on PubMed.
Clinically translatable anti-fibrotic nanosuspension for inhaled treatment of idiopathic pulmonary fibrosis.
Lee D, Kong B, Kwak G … +5 more , Kang B, Swaby C, Fanaroff R, Sidhaye V, Suk JS
Drug Deliv Transl Res · 2026 May · PMID 41004077 · Publisher ↗
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by chronic pulmonary fibrosis, irreversible lung function decline, and high mortality rate. Oral nintedanib (NTB) is one of the...
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by chronic pulmonary fibrosis, irreversible lung function decline, and high mortality rate. Oral nintedanib (NTB) is one of the rare anti-fibrotic drugs clinically available for managing the condition but suffers from poor bioavailability and lung delivery efficiency as well as numerous off-target adverse effects. To address these critical limitations, we developed a nanosuspension (NS) formulation of NTB (NTB-NS) for inhaled treatment of IPF. The formulation is composed entirely of FDA-approved materials, including NTB and polysorbate 80, a surfactant approved for respiratory use in a clinic, and can be freeze-dried to a powder form for long-term storage and remote shipping without perturbing the physicochemical properties and drug activity. NTB-NS locally administered via oropharyngeal administration exhibited favorable pharmacokinetics over the standard oral administration of nintedanib esylate (NTB-esy), resulting in comprehensive anti-inflammatory and anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrosis. Notably, locally administered NTB-NS, but not oral NTB-esy, normalized several key lung function parameters in the model despite the use of 60-fold and 3-fold lower dose and dosing frequency, respectively. The findings here may open a new avenue for the treatment of IPF and potentially other fibrotic lung diseases in the clinic.
Correction: Dual phage-incorporated electrospun polyvinyl alcohol-eudragit nanofiber matrix for rapid healing of diabetic wound infected by Pseudomonas aeruginosa and Staphylococcus aureus.
Suchithra KV, Hameed A, Surya S … +2 more , Mahammad S, Arun AB
Drug Deliv Transl Res · 2026 Jan · PMID 40988002 · Publisher ↗
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