Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
Impact of solvent choice during microfluidic manufacture on the in vivo performance of liposomal doxorubicin.
Lindsay S, Holm R, Shah S … +1 more , Perrie Y
Drug Deliv Transl Res · 2026 Mar · PMID 41772349 · Publisher ↗
Microfluidics offers a reproducible approach to liposome manufacture; however, the impact of solvent choice on formulation performance remains underexplored. Here, we investigated whether solvent selection during microfl...
Microfluidics offers a reproducible approach to liposome manufacture; however, the impact of solvent choice on formulation performance remains underexplored. Here, we investigated whether solvent selection during microfluidic manufacturing influences liposome performance by assessing its effect on the drug release and biodistribution of liposomal doxorubicin, using rotary evaporation as a conventional method of comparison. PEGylated liposomes (DSPC:Chol:DSPE-PEG2000, 3:1:1 w/w) were prepared using a staggered herringbone microfluidic mixer, with lipids dissolved in either ethanol or Transcutol, and compared with liposomes produced by rotary evaporation and extrusion. All formulations were actively loaded with doxorubicin via an ammonium sulphate gradient, purified by tangential flow filtration, and characterised for size, polydispersity, and drug loading. The three formulations (two microfluidic (ethanol vs Transcutol) and one rotary evaporation control) were intravenously administered to Sprague-Dawley rats (1 mg/kg), and doxorubicin concentrations in plasma and tissues were quantified using LC-MS. Although solvent choice produced liposomes with broadly comparable physicochemical properties (~ 100-120 nm, PDI < 0.25, encapsulation > 90%), Transcutol-based microfluidic liposomes showed prolonged and higher concentrations of doxorubicin within the plasma and tissue samples compared with liposomes produced by ethanol microfluidics and rotary evaporation. By contrast, the manufacturing method alone (microfluidics using ethanol as the solvent versus rotary evaporation) did not significantly influence biodistribution. These findings highlight solvent selection as an important parameter in microfluidic liposome manufacture, demonstrating that matching standard critical quality attributes and in vitro release behaviour alone may be insufficient to ensure comparable in vivo performance.
Transdermal patches loaded with etoricoxib nanocrystals as a remedy and prophylactic approach against progression of knee osteoarthritis.
Ahmed LM, Hosny OH, Abdelqader ZS … +2 more , Mohamed FA, Elfaham TH
Drug Deliv Transl Res · 2026 Feb · PMID 41741909 · Publisher ↗
Osteoarthritis (OA) is a heterogeneous and multifactorial disorder that affects the entire joint organ. It is a major global public health concern, impacting more than 500 million individuals worldwide. The onset and pro...
Osteoarthritis (OA) is a heterogeneous and multifactorial disorder that affects the entire joint organ. It is a major global public health concern, impacting more than 500 million individuals worldwide. The onset and progression of OA are driven by a complex interplay of factors and modifiable risks such as obesity and joint injury. Consequently, OA imposes a substantial burden on patients' quality of life and on society, owing to increased healthcare expenditures and reduced work productivity. The purpose of this study is to assess the therapeutic efficacy of transdermal patches loaded with etoricoxib nanocrystals (ETX-NCs, previously prepared and evaluated) in the treatment and reduction of osteoarthritis exacerbation. ETX-NCs patches of various polymers were prepared using solvent evaporation technique. The prepared patches were evaluated for drug content, thickness, moisture uptake, folding endurance, in vitro drug release, and skin permeation properties. The prepared patches based on HPMC, CMC Na, and PVA demonstrated uniformity, flexibility, smooth surface morphology and high drug content, along with acceptable physicochemical properties. Among these, the CMC Na based nanocrystal patches exhibited the most prolonged drug release (73.76 ± 2.38%). HPMC and CMC Na based patches showed promising skin penetration of 79.64 ± 1.20 μg/cm and 44.06 ± 2.72 μg/cm, with corresponding flux values of 16.13 ± 0.21 μg/cm/h and 8.08 ± 0.47 μg/cm/h, respectively. Based on in vivo findings, the prepared ETX-NCs patches found to successfully alleviate OA symptoms within short duration (5 days), also protecting against disease progression.
Correction: Preparation, characterisation, and testing of reservoir-based implantable devices loaded with tizanidine and lidocaine.
Picco CJ, Bhalerao MS, Fandino OE … +6 more , Magill ER, Anjani QK, Acheson JG, Donnelly RF, Domínguez-Robles J, Larrañeta E
Drug Deliv Transl Res · 2026 Jun · PMID 41735714 · Full text
Abstract loading — click title to view on PubMed.
Active learning in pharmaceutical 3D printing: a multi-dataset comparison.
Elbadawi M, Kafoor NFA, Li H … +3 more , Protopapa C, Vlachou M, Gaisford S
Drug Deliv Transl Res · 2026 Feb · PMID 41735713 · Publisher ↗
Machine learning (ML) is expected to accelerate the developments of three-dimensional (3D) printed medicines. Despite ML's potential, the need for large datasets can hinder progression, as 3D printing remains an emerging...
Machine learning (ML) is expected to accelerate the developments of three-dimensional (3D) printed medicines. Despite ML's potential, the need for large datasets can hinder progression, as 3D printing remains an emerging pharmaceutical manufacturing technology. This study explores an ML strategy called active learning (AL), which harnesses the benefits of ML whilst applicable with small datasets. AL was tested to predict the printability of three 3D printing datasets: 1437 fused deposition modelling (FDM), 650 vat polymerisation and 297 selective laser sintering (SLS) formulations. The analysis revealed that accuracies of 60% can be achieved when starting with 33 formulations, and subsequent increases in training data size enhances predictive performance. Furthermore, AL was found to achieve 100% predictive accuracy, which is the highest recorded to date for pharmaceutical 3D printing. These initial findings highlight AL's advantages over traditional ML modelling and showcase its potential to accelerate the development of 3D printing medicines. This research also demonstrates the potential of modelling with small datasets, thereby widening ML's application in pharmaceutical research.
Quality by design (QbD)-guided development of PEGylated nanostructured lipid carriers of donepezil for intranasal delivery.
Desai A, Desai N, Vora LK … +1 more , Shah P
Drug Deliv Transl Res · 2026 Feb · PMID 41735712 · Publisher ↗
Neurological disorders (ND) pose a major global health challenge, in large part due to the restrictive nature of the blood-brain barrier (BBB), which prevents most therapeutic agents from reaching the central nervous sys...
Neurological disorders (ND) pose a major global health challenge, in large part due to the restrictive nature of the blood-brain barrier (BBB), which prevents most therapeutic agents from reaching the central nervous system (CNS). Intranasal delivery (IN) offers a non-invasive and patient-friendly route to bypass the BBB via the olfactory and trigeminal pathways, but its success requires advanced nanocarrier systems capable of enhancing drug retention, stability, and controlled release. In this study, a Quality by Design (QbD) framework was applied to systematically develop and optimize 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-PEG)-functionalized nanostructured lipid carriers (NLCs) using Donepezil (DPZ) as a model drug. Through sequential risk assessment, Plackett-Burman screening design (PBD), and Central Composite Design (CCD) optimization, the Critical Formulation Variables (CFVs) and Critical Process Parameters (CPPs) influencing particle size (PS) and entrapment efficiency (%EE) were identified. The optimized DSPE-PEG-NLCs exhibited nanoscale size (133.4 ± 2.91 nm), high %EE (89.5 ± 1.51%), strong mucin binding (84.6 ± 2.68%), and a distinct core-shell morphology. In vitro and ex vivo studies confirmed a biphasic and sustained drug release up to 60 h & 67 h, outperforming uncoated NLCs and conventional formulations. Stability studies demonstrated improved preservation under refrigerated conditions. Beyond DPZ, the QbD-guided strategy presented here provides a generalizable and regulatory-aligned platform for designing IN nanocarriers, paving the way for reproducible, scalable, and translational drug delivery systems targeting a wide range of ND.
Effects of borneol on pharmacokinetics and tissue distribution of tetramethylpyrazine in transdermal patch.
Cui L, Zha L, Mei J … +4 more , Xue R, Wang J, Zhang Z, Ma Y
Drug Deliv Transl Res · 2026 Feb · PMID 41735711 · Publisher ↗
Tetramethylpyrazine (TMP), a potent coronary vasodilator, enhances myocardial perfusion and shows promise for treating cardiovascular disorders. Its clinical utility is limited, however, by the short half-life of convent...
Tetramethylpyrazine (TMP), a potent coronary vasodilator, enhances myocardial perfusion and shows promise for treating cardiovascular disorders. Its clinical utility is limited, however, by the short half-life of conventional tablets and injections, which necessitates frequent dosing. To overcome this drawback, we developed a transdermal patch that co-loadsTMP and borneol (BO-TMP). After optimization, patches containing 3% borneol as a permeation enhancer, exhibiting the highest cumulative penetration amount of TMP (6.80 mg·cm over 24 h) in vitro. Pharmacokinetic profiling revealed that borneol markedly improved TMP exposure. C rose from (1.96 ± 0.27) to (2.88 ± 0.72) mg/L, and AUC expanded from (47.73 ± 6.93) to (73.18 ± 13.86) mg/L*h in plasma; C rose from (12.99 ± 2.28) to (15.33 ± 4.24) mg/L, and AUC expanded from (220.86 ± 53.88) to (374.55 ± 111.84) mg/L*h in skin, C rose from (0.87 ± 0.12) to (6.20 ± 0.84) mg/L, and AUC expanded from (13.08 ± 3.35) to (79.80 ± 16.31) mg/L*h in heart when BO-TMP patches were administrated compared with TMP patches. Tissue distribution studies demonstrated that borneol redirected TMP distribution, shifting the order of tissue abundance from liver > kidney > brain > spleen > heart > lung to liver > kidney > heart > brain > spleen > lung, and thus enriched the drug at its therapeutic site. By selectively heightening cardiac exposure, the BO-TMP patch transform TMP into a cardiovascular-focused therapy, offering a convenient, long-acting dosage from with the potential to enhance efficacy and improve patient outcomes.
Correction to: Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery.
Thakur RRS, Tekko IA, Al-Shammari F … +3 more , Ali AA, McCarthy H, Donnelly RF
Drug Deliv Transl Res · 2026 Feb · PMID 41721024 · Publisher ↗
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Fabrication and characterization evaluation of sustained-release dissolving microneedles with skin soothing function.
Yang Y, Zhang T, Zhang Y … +2 more , Liu L, Meng F
Drug Deliv Transl Res · 2026 Feb · PMID 41721023 · Publisher ↗
In recent years, microneedles (MNs) have drawn significant attention as a new strategy for drug delivery. Especially, dissolving microneedles (DMNs) are the most suitable system for their degradability and low biological...
In recent years, microneedles (MNs) have drawn significant attention as a new strategy for drug delivery. Especially, dissolving microneedles (DMNs) are the most suitable system for their degradability and low biological hazard. However, MNs will inevitably cause skin irritation, which needs to be improved. The goal of this study is to develop soothing and sustained-release DMNs to reduce skin irritation during drug delivery. The MNs were successfully fabricated using biocompatible sodium hyaluronate, resilient hydroxyethyl cellulose, and γ-polyglutamic acid, which possess skin repair functions. An orthogonal experiment was designed and the performance of different DMNs was characterized to explore the optimal formation, including morphology and mechanical performance. We found that the optimal formulation was 13% HA-Na, 7% HEC and 5% γ-PGA at 30℃ for 3 h. The morphology of the DMNs had structural integrity with sharp tips and a uniform array. They could withstand a force of up to 20 N without fracture, demonstrating sufficient mechanical strength for skin penetration. Subsequently, further characterization of the optimal formulation of DMNs was performed, including skin penetration ability, compression resistance, and in vitro/in vivo dissolution behavior. The DMNs successfully penetrated porcine skin and simulated skin models under a force of 2 N. In vivo dissolution in mouse skin was completed within 1 h, supporting their soothing and sustained-release potential. The skin repair function was validated through a skin irritation experiment; the mice treated by DMNs with 5% γ-PGA had no erythema and edema during the whole process and the pinholes were observed to fully disappear in 5 min, indicating rapid skin repair function. Through these tests, our fabricated DMNs possessed soothing and sustained-release properties and skin repair function. To further realize the drug delivery application of the DMNs, some experiments should be conducted in the future, including drug loading and transdermal release performance.
Microbubble-free mechanical sonoporation for MR-guided drug delivery in solid tumours: a proof-of-concept study.
Patrucco D, Capozza M, Garello F … +4 more , Mangia A, Carrera C, Tarso G, Terreno E
Drug Deliv Transl Res · 2026 Feb · PMID 41712162 · Publisher ↗
Ultrasound (US)-mediated drug delivery is a promising strategy for localised, minimally invasive molecular transport, typically relying on microbubble-assisted sonoporation. However, clinical translation is limited by th...
Ultrasound (US)-mediated drug delivery is a promising strategy for localised, minimally invasive molecular transport, typically relying on microbubble-assisted sonoporation. However, clinical translation is limited by the short half-life, cost, and cytotoxicity of exogenous microbubbles. In this proof-of-concept study, we present a microbubble-free, mechanically driven sonoporation approach for intracellular delivery of hydrophilic agents, monitored non-invasively by magnetic resonance imaging (MRI). Using a low-intensity, non-focused ultrasound protocol (1 MHz, MI 0.25, 25% duty cycle, 1 Hz PRF) we achieved efficient intracellular internalisation of the MRI contrast agent Gadoteridol (~ 7 × 10⁹ Gd ions/cell) in vitro while maintaining > 70% cell viability and demonstrating complete membrane resealing within 30 min. Co-delivery with propidium iodide (PI) was confirmed by fluorescence microscopy and MRI, showing cytosolic distribution with negligible passive uptake in non-sonoporated controls. Compared to established permeabilisation methods (electroporation, pinocytosis, hypotonic swelling), microbubble-free sonoporation produced higher uptake with lower oxidative stress. In vivo experiments in K562 tumour-bearing mice showed that intravenous co-administration of Gadoteridol and PI followed by local sonoporation yielded significantly enhanced and prolonged T1 MRI contrast and increased intratumoural accumulation of both agents. These findings establish microbubble-free sonoporation as an effective, controllable technique for intracellular delivery, with the added benefit of MRI-based monitoring. This strategy addresses key limitations of microbubble-based methods and holds strong potential for image-guided therapeutic applications in solid tumors.
PMVE/MA-based microneedle patches for rapid transdermal delivery of vitamin B12: fabrication and evaluation.
Saurabh S, Kumar D, Soni S
Drug Deliv Transl Res · 2026 Feb · PMID 41708905 · Publisher ↗
Vitamin B12 (cyanocobalamin) deficiency is a prevalent global health issue which has been historically treated with oral supplements or intramuscular injections. In case of pernicious anemia, there is poor absorption of...
Vitamin B12 (cyanocobalamin) deficiency is a prevalent global health issue which has been historically treated with oral supplements or intramuscular injections. In case of pernicious anemia, there is poor absorption of Vitamin B12 in the intestine, so injection is a typical treatment option. However, injections are painful and require a trained medical professional, which can often lead to the patient visiting clinics, thereby leading to patient non-compliance. In order to overcome these disadvantages, this research investigates an alternative, minimally invasive, and patient-friendly self-administration option, transdermal delivery via dissolvable microneedle (MN) patch. We fabricate a poly (methyl vinyl ether/maleic acid) (PMVE/MA) based MN patch, a biocompatible material, for the rapid delivery of cyanocobalamin. An in-house developed polydimethylsiloxane (PDMS) mold was used to prepare the MN patch. The MN patches were characterized by optical microscopy and scanning electron microscopy (SEM) to determine MN dimensions and morphology. Mechanical strength and skin penetration ability of the MNs were assessed through a universal testing machine (UTM) and a parafilm layer model. The findings suggest that 20% PMVE/MA formulation offered sufficient mechanical strength for skin penetration and more than 90% insertion efficiency which is total number of holes created by all the MNs. Dissolution of the needles was achieved within 45 s in agarose phantom and within 120 s in porcine skin. In vitro Franz diffusion experiments revealed continuous release, achieving a cumulative release mass of ~ 229 µg of vitamin B12 within 210 min. UV-Vis and FTIR analysis confirmed excellent B12 stability in the MN patch up to 60 days. The reported observations emphasize the advantages and the translational potential of PMVE/MA-based dissolvable MN patch as a safe, effective, and user-friendly system for the transdermal delivery of vitamin B12.
Emerging ophthalmic drug delivery.
Thakur RRS, Vora LK, Herrero-Vanrell R
Drug Deliv Transl Res · 2026 Apr · PMID 41708904 · Publisher ↗
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Comparative analysis of clinically approved lipid nanoparticles for intranasal siRNA delivery against SARS-CoV-2.
Zhang Y, Johansen MD, Ledger S … +9 more , Shipley R, Zhao G, Moles E, Turville S, Thordarson P, Hansbro PM, Kavallaris M, Kelleher AD, Ahlenstiel CL
Drug Deliv Transl Res · 2026 Feb · PMID 41708903 · Publisher ↗
SARS-CoV-2 continues to circulate globally, with persistent hospitalizations, despite a successful global vaccination strategy. We have developed highly conserved, antiviral short interfering (si)RNA and demonstrated in...
SARS-CoV-2 continues to circulate globally, with persistent hospitalizations, despite a successful global vaccination strategy. We have developed highly conserved, antiviral short interfering (si)RNA and demonstrated in vivo antiviral efficacy following intranasal treatment of mice with naked siRNA. To enhance antiviral efficacy and siRNA protection, in this study we investigated the use of LNP packaging to improve delivery and efficacy. We examined three clinically approved lipid nanoparticle (LNP) formulations that mimic the compositions of Alnylam's Onpattro (MC3), Moderna's Spikevax (SM-102), and Pfizer-BioNTech's Comirnaty (ALC-0315) RNA-based therapeutics, to identify the optimal formulation for antiviral siRNA therapeutic respiratory delivery and antiviral efficacy. All LNP formulations assessed showed successful delivery of siRNA to respiratory cells in vitro and provided effective silencing of siRNA targeted SARS-CoV-2 genes. However, the MC3-based LNP-siRNA (MC3 LNP-siRNA) treatment elicited the least off-target immune activation, with no induction of interferon stimulated genes. Additionally, the MC3 LNP-siRNA remained effective when administered 24 h post-infection, significantly reducing viral RNA levels in vitro. Chemical modification of siRNA with 2'‑O‑methyl incorporation further attenuated immune activation, without compromising efficacy. In vivo intranasal delivery of MC3 LNP-siRNA was generally well tolerated, with no adverse effects on body weight or pulmonary function at therapeutic doses, although mild pulmonary leukocyte infiltration was observed at higher or repeated doses. Our study demonstrates that LNP-encapsulated and chemically modified siRNAs can provide an effective and mutation-resilient antiviral strategy. This study compares clinically relevant LNP formulations for siRNA delivery to the respiratory tract, demonstrating that MC3-based LNPs offer a promising platform for safe and effective RNA therapeutic delivery.
Comparative study of thiolated and alkenylated functionalized β-CDs as highly mucopenetrating and mucoadhesive drug delivery systems.
Kosti EM, Huber SD, Mair A … +3 more , Gintsburg D, Bernkop-Schnürch A, Kali G
Drug Deliv Transl Res · 2026 Feb · PMID 41703368 · Publisher ↗
Within this study, thiolated and alkenylated β-cyclodextrins were developed as novel mucoadhesive excipients capable of interacting with mucosal surfaces and prolonging the residence time of incorporated drugs at absorpt...
Within this study, thiolated and alkenylated β-cyclodextrins were developed as novel mucoadhesive excipients capable of interacting with mucosal surfaces and prolonging the residence time of incorporated drugs at absorption sites, thereby potentially enhancing their bioavailability. For this purpose, cysteine-, cysteamine-, allylcarbamate-, and methacrylate-functionalized oligosaccharides were synthesized, and the resulting structures were identified by H NMR spectroscopy, Ellman's and disulfide bond tests, and iodometry. The thiol and double bond content, as well as the stability of these functional groups at 37 °C, over 4 h, were evaluated. Alkenylated β-cyclodextrins showed significantly higher stability in aqueous solution compared to the thiolated products with oxidative sensitivity. Furthermore, the cytotoxicity and rheological, mucodiffusive, and mucoadhesive properties of the derivatives were assessed to elucidate their potential as multifunctional excipients for mucosal drug delivery. The cytotoxicity study confirmed that all derivatives were non-toxic within 4 h of incubation. Rheological measurements showed that β-CD highly modified with allylcarbamate exhibited a 15-fold increase in dynamic viscosity after incubating with intestinal mucus compared to the native β-CD. Regarding mucopenetration, β-CD cysteine was able to penetrate the mucus by more than 3% per 5 cm in 24 h. The results on porcine intestine revealed the superiority of thiolated derivatives in mucoadhesion, with at least 98% of the samples remaining on the intestinal tissue after 3 h of rinsing. For alkenylated β-CD with a similar degree of modification, low mucoadhesiveness was detected, but it was increased significantly with the degree of modification. The current study compares various mucoadhesive approaches and demonstrates that thiolated derivatives are more effective than alkenylated derivatives for mucosal drug delivery, but are less stable in physiological fluids.
Fibroblast-derived small extracellular vesicles loaded with tacrolimus enhances dermal delivery and alleviates cytokine-overdriven skin inflammation.
Nanthakumar P, Law JX, Ng SF
Drug Deliv Transl Res · 2026 Feb · PMID 41703367 · Publisher ↗
Long COVID has been increasingly linked to chronic inflammatory skin conditions driven by cytokine overproduction. Topical tacrolimus, a calcineurin inhibitor, is commonly used to manage such conditions due to its immuno...
Long COVID has been increasingly linked to chronic inflammatory skin conditions driven by cytokine overproduction. Topical tacrolimus, a calcineurin inhibitor, is commonly used to manage such conditions due to its immunosuppressive properties. However, due to poor dermal penetration, tacrolimus oftens produce to suboptimal efficacy and adverse effects such as local irritation and burning sensation. Effective management of chronic inflammatory skin conditions linked to long COVID necessitates targeted, controlled drug delivery into deeper skin layers to modulate excessive cytokine production and attenuate localized inflammation. This study explores fibroblast-derived small extracellular vesicles (sEVs) as a new controlled delivery vehicle for tacrolimus. The sEVs were isolated using sucrose-cushioned density ultracentrifugation and characterized by TEM, NTA, Dot blot, and MicroBCA assay, confirming their successful isolation and purity. Tacrolimus was encapsulated into sEVs via sonication, with successful drug loading confirmed by morphological and physicochemical characterization. The resulting Tac-sEVs exhibited an encapsulation efficiency of 79.19% ± 0.01. Franz diffusion studies revealed a rapid initial release within the first 10 h, followed by sustained higher release over time. Tape-stripping demonstrated significantly deeper dermal penetration of tacrolimus loaded sEVs (Tac-sEVs) compared with commercial tacrolimus ointment and free drug. Both tacrolimus and Tac-sEVs downregulated IFN-γ, GCS-F, IL-2, and IL-4 expression, indicating potent suppression of SARS-CoV-2 spike glycoprotein-induced cytokine overproduction. PKH-26 fluorescence labelling confirmed efficient cellular uptake, while cytotoxicity assays (Alamar Blue, CCK-8) showed high cell viability for both formulations. In summary, these results position Tac-sEVs as a safe and promising therapeutic platform for cytokine-driven inflammatory skin diseases associated with long COVID, meriting further clinical investigation.
Statistical optimization of chitosan-based synthesis strategies to generate albumin nanoparticles.
Martín-Escaño A, Barbuzano C, Rodríguez-Díaz JM … +1 more , Pérez-Herrero E
Drug Deliv Transl Res · 2026 Feb · PMID 41699362 · Publisher ↗
Albumin-based nanoparticles (NPs) are typically synthesized by harsh conditions-based methods that limit their application in clinics and can seriously damage the entrapped drug and even their base material. Despite the...
Albumin-based nanoparticles (NPs) are typically synthesized by harsh conditions-based methods that limit their application in clinics and can seriously damage the entrapped drug and even their base material. Despite the potential of the use of chitosan (CS) as stabilizing agent by adapting the ionic gelation method or by adding CS as a coating to albumin NPs generated by desolvation, the influential factors of these methods have not yet been studied. In this article, these synthesis approaches have been optimized by a 2-step DoE-based methodology (a screening process with fractional designs plus a response surface methodology using central composite designs). The application of the ion gelation method to produce albumin-based NPs generates sizes from 66 to 1017 nm, PDI (polydispersity index) values of 0.3-0.6 and surface charges (ZP) from neutral to positive (> 20 mV). The fitted models of the responses depend on four factors (albumin and CS concentration, CS pH and CS:albumin mass ratio). On the other hand, the modification of the desolvation method using CS as a stabilizing coating generates 37-1305 nm NPs, with PDI between 0.4 and 0.7 and highly positive ZP (20-40 mV). In this case, the approximate models for the responses depend on four main effects (albumin and CS concentration, pH of CS and albumin:EtOH volume ratio). Furthermore, in this work the best combinations of factors and levels that allow minimizing PDI and obtaining the minimum and maximum expected values for mean size and ZP of NPs were determined for both synthesis methods. Focusing on the minimum possible PDI, the predicted values for the ion gelation- and desolvation-based methods are 0.363 and 0.341, respectively, which are achieved with values of [BSA] (mg/ml), [CS] (mg/ml), CS pH and CS:BSA or BSA:EtOH ratios (mL:mL) of {2.3,1.4,2.2,1:7.3} and {10,0.5,1.8,1:1}, respectively. These optimized conditions yield acceptable size and ZP values for the ion gelation-based (27.7 nm; 16.4 mV) and optimal values for the desolvation-based (146.2 nm; 29.5 mV).
Effective topical delivery of minoxidil via chitosan coated nanocapsules to remodel microenvironment of dermal follicle for hair regeneration.
Lee JS, Park TE, Son P … +6 more , Oh H, Lee SB, Kim S, Lee JH, Kim KS, Choi WI
Drug Deliv Transl Res · 2026 Feb · PMID 41688806 · Publisher ↗
Hair loss is a prevalent dermatological disorder that significantly affects quality of life. Among FDA approved treatments, topically applied minoxidil is commonly used. Nevertheless, its low water solubility necessitate...
Hair loss is a prevalent dermatological disorder that significantly affects quality of life. Among FDA approved treatments, topically applied minoxidil is commonly used. Nevertheless, its low water solubility necessitates use of irritating solvents which hinder its clinical administration. Since these solvents usually cause adverse reactions, nanotechnology-based carriers have emerged as promising strategies for topical delivery of minoxidil. Thus, we prepared topical delivery nanocarriers, i.e., chitosan-coated nanocapsules (ChiNCs), to increase percutaneous delivery through intrinsic characteristics of chitosan and to increase encapsulation of minoxidil into the nanocarriers. ChiNCs were prepared through simple nanoprecipitation and encapsulated in high amounts of minoxidil. The minoxidil-loaded ChiNCs (MXD@ChiNCs) were evaluated for their physicochemical characteristics, colloidal stability, release profile, skin penetration, cytotoxicity, proliferation, hair growth via animal, and histological analyses. MXD@ChiNCs were successfully loaded with 50 wt.% of MXD and maintained good stability. Additionally, release profile of MXD from MXD@ChiNCs exhibited sustained release behavior and improved skin penetration. Particularly, ChiNCs showed no cytotoxicity in skin-related cell lines and did not influence cell proliferation. MXD@ChiNCs demonstrated dose-dependent therapeutic efficacy and considerably boosted hair regrowth compared to other MXD formulations, as evidenced by macroscopic and histological results. These observations highlight potential of MXD@ChiNCs as topical delivery system for alopecia.
A novel approach to fat reduction: integrating traditional Chinese medicine with a dissolving MNs.
Wang C, Liu F, Ge J … +6 more , Zhao S, Ma X, Yi S, Ma Z, Zhao Y, Zhuang J
Drug Deliv Transl Res · 2026 Feb · PMID 41678096 · Publisher ↗
Obesity is not only a direct cause of health problems, but is also closely related to the incidence rate of a variety of noncommunicable diseases. Intervention for obesity requires high self-discipline and compliance fro...
Obesity is not only a direct cause of health problems, but is also closely related to the incidence rate of a variety of noncommunicable diseases. Intervention for obesity requires high self-discipline and compliance from individuals, which often makes weight loss less smooth and prone to rebound. In this study, we prepared a dissolving microneedle (MN) loaded with compound traditional Chinese medicine (TCM). The base material was composed of a mixture of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP), which met the requirements of solubility and sufficient mechanical properties. For the drug, we chose the Huatanqushi formula, which has a clear fat-reducing effect in clinical practice and is food and medicine homology. The results showed that the MN can penetrate the stratum corneum, rapidly release drugs in the dermis of the abdominal wall, alleviate the inflammatory state of local adipose tissue, regulate systemic lipid metabolism, and ultimately achieve weight loss. This MN patch is suitable for busy office workers to use conveniently, avoiding the discomfort of oral medication and the drawbacks of a large dosage and long medication time. It can effectively intervene in obesity with a minimal effect on the body.
Pharmacokinetic studies and synergistic antitumor effects of cannabichromene and cannabidiol in drug-resistant breast cancers.
Aare M, Padakanti SC, Bagde A … +4 more , Lazarte JM, Dev S, Lewis C, Singh M
Drug Deliv Transl Res · 2026 Feb · PMID 41670942 · Publisher ↗
Triple-negative breast cancer (TNBC) is highly aggressive with limited treatment options, and resistance to doxorubicin (DOX) further compromises outcomes. Cannabinoids such as cannabichromene (CBC) and cannabidiol (CBD)...
Triple-negative breast cancer (TNBC) is highly aggressive with limited treatment options, and resistance to doxorubicin (DOX) further compromises outcomes. Cannabinoids such as cannabichromene (CBC) and cannabidiol (CBD) possess anticancer properties, but their combined effects in resistant TNBC remain unexplored. This study evaluated the antitumor efficacy of a CBC + CBD combination against DOX-resistant (DOX-RT) TNBC using in vitro, in vivo, and pharmacokinetic models. Cytotoxicity was assessed in DOX-RT MDA-MB-231 cells using 2D and 3D assays, with synergy confirmed by combination index (CI) analysis. Cell cycle and invasion assays were performed. Xenograft studies were conducted in BALB/c nude mice bearing DOX-RT tumors treated intraperitoneally with CBC (10 mg/kg), CBD (20 mg/kg), or CBC + CBD. Pharmacokinetics were evaluated in rats, complemented by GastroPlus™ simulations. CBC + CBD synergistically inhibited cell growth induced G0/G1 arrest, and reduced invasiveness by ~ 55% in a Transwell Matrigel invasion assay. In xenografts, combination therapy reduced tumor volume by two-folds compared to single treatments and fourfolds versus control. Western blotting revealed downregulation of MEK/ERK, PI3K/AKT/mTOR, Cyclin D1, CDK6, SOD2, and NF-κB. Pharmacokinetic studies showed co-administration increased Cmax and AUC without altering Tmax, supported by simulations predicting enhanced jejunal absorption. CBC + CBD co-therapy demonstrates synergistic efficacy against resistant TNBC by inhibiting oncogenic pathways and enhancing systemic exposure. This first study of its kind highlights CBC + CBD as a promising strategy to overcome DOX resistance in TNBC.
A mechanical reprogramming: synergistic tumor microenvironment normalization improves nano-immunotherapy delivery in prostate cancer via multiphysics modeling.
Mirala F, Soltani M
Drug Deliv Transl Res · 2026 Feb · PMID 41665856 · Publisher ↗
There is a poor response of prostate cancer to immunotherapies because of dysfunctions in the tumor microenvironment (TME) characteristics, like abnormal vasculature structure, stiffened stroma, increased interstitial fl...
There is a poor response of prostate cancer to immunotherapies because of dysfunctions in the tumor microenvironment (TME) characteristics, like abnormal vasculature structure, stiffened stroma, increased interstitial fluid pressure (IFP), and regions of hypoxia. However, the existing computational modelings are unable to tackle this issue, as they are based on two-dimensional (2D) geometry that ignores TME properties (like TME biphasic composition) and interaction between cancer and immune cells. To address this knowledge gap, this paper offers a patient-specific multiphysics model for prostate cancer. The proposed model is based on three-dimensional (3D) geometry obtained from magnetic resonance imaging (MRI) and combines three complementary approaches to normalizing the tumor microenvironment: vascular normalization via anti-angiogenic therapy, stromal normalization via extracellular matrix softening, and immune checkpoint blockade. One important new aspect of this work is that new nanoparticle delivery models have been developed for 20-100 nm nanoparticles (NP) delivering immunotherapy agents. These equations explicitly incorporate interactions between the components of the TME and directly account for mechanical stress induced by tumor growth, enabling mathematical modeling of physical TME changes and their subsequent impact on the dynamics of immune cells (such as cytotoxic T cells (CD8 + T cells), regulatory T cells (Treg), and pro-inflammatory macrophages (M1-like)/anti-inflammatory macrophages (M2-like) and cancer cells. This capability is absent in previous models. The other important novelty is that for the first time in a prostate cancer model, factors for vascular and stromal normalization and immunotherapy have been incorporated in a 3D geometry. The parameters of this model have been optimized based on literature and preclinical trial data related to immunology and tumors. The sensitivity analysis has confirmed that all therapeutic factors, optimized vascular function (functional vessel density increases from 43 to 112 cm/cm), reduced stromal solid stress (decrease in shear modulus from 10.4 to 6.1 kPa), as well as a 70% reduction in IFP (from 1471 to 441 Pa), in combination contribute to a 30% increase in accumulation of nanoparticles in the tumor, 60% increase in the ratio of CD8 + /Tregs, a 45% decrease in the ratio of M1/M2 macrophages, a 15% reduction in the tumor hypoxia gradient, and a 40% decrease in the size of the tumor within 50 days. This model can thus provide a clinically applicable tool for predicting the efficacy of nano-immunotherapy in prostate cancer. Experimental confirmation is required to better evaluate NP toxicity.
Computational study of Durysta implant for glaucoma treatment: drug dispersion and aqueous humor flow in the anterior chamber.
Kumar A, Babu AB, Flarence M
Drug Deliv Transl Res · 2026 Feb · PMID 41665855 · Publisher ↗
Glaucoma is a leading cause of irreversible blindness, with current treatment strategies focusing on reducing the intraocular pressure (IOP). The Durysta (bimatoprost) intracameral implant offers a sustained-release alte...
Glaucoma is a leading cause of irreversible blindness, with current treatment strategies focusing on reducing the intraocular pressure (IOP). The Durysta (bimatoprost) intracameral implant offers a sustained-release alternative to conventional eye drops by continuously delivering medication directly into the anterior chamber (AC). This study employs advanced computational modeling using ANSYS Fluent to investigate the interaction between aqueous humor (AH) flow and drug distribution following Durysta implantation. Drug transport is modeled using the unsteady convection diffusion equation, and concentration profiles are analyzed at different times: 10 min, 30 min, 1 h, 1 day, 15 days, 30 days, and 60 days. The results show that AH circulation significantly influences by Durysta implant, with flow-driven mixing facilitating its distribution across ocular tissues. In the early phase, high concentration zones appear near the implant, while long-term simulations demonstrate sustained and uniform drug distribution throughout the AC. These findings advance the understanding of sustained intraocular drug delivery and establish a computational framework to guide the optimization of future implant designs, aiming to improve therapeutic outcomes in glaucoma management.
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