Drug Delivery And Translational Research[JOURNAL]
Sun
200 papers
Development of sustained release injectable phospholipid-based phase transition gel matrixed with Piracetam and cannabidiol loaded nanoemulsion for amelioration of Alzheimer's therapy.
Shahrukh M, Adil M, Hasan N … +1 more , Ahmad FJ
Drug Deliv Transl Res · 2026 Mar · PMID 41299112 · Publisher ↗
Alzheimer's disease (AD) is an incurable neurological disorder and the primary cause of dementia globally, yet therapeutic options remain limited by poor drug efficacy, low patient adherence, and the restrictive blood-br...
Alzheimer's disease (AD) is an incurable neurological disorder and the primary cause of dementia globally, yet therapeutic options remain limited by poor drug efficacy, low patient adherence, and the restrictive blood-brain barrier (BBB), which prevents over 98% of small molecules from reaching the brain. Piracetam (PIRA), a nootropic agent, and cannabidiol (CBD), a neuroprotective compound, have shown potential in addressing AD-related oxidative stress, inflammation, and neurotransmitter imbalance. However, both drugs exhibit short plasma half-lives, requiring frequent dosing that may reduce patient compliance. To address these challenges, we developed a sustained-release phospholipid phase-transition gel (PPTG) depot incorporating a PIRA-CBD nanoemulsion. A combination index study demonstrated potent synergy at a 1:5 CBD: PIRA ratio. Optimization of the nanoemulsion was carried out using a Box-Behnken design, which explored oil concentration (Capryol 90), Smix (Tween 20: Cremophor ELP), and stirring speed as key variables. A mean particle size of 137.8 nm, a PDI of 0.155, and a zeta potential of -7.587 mV were all observed in the formulation that was optimized. Upon subcutaneous injection, the PPTG showed excellent injectability and formed a stable depot in vivo, as confirmed by gamma scintigraphy. In vitro studies revealed sustained release of 90.538 ± 2.62% PIRA and 87.202 ± 2.16% CBD over 96 h, compared to rapid release from the drug solution. This study introduces a novel phospholipid-based phase-transition gel depot incorporating PIRA-CBD nanoemulsion, which provides sustained, targeted brain delivery to enhance therapeutic efficacy and improve patient compliance in Alzheimer's disease management.
Ectoine as a multifunctional molecule: biotechnological production and pharmaceutical applications.
Ferreira P, Ataide JA, Babaie S … +7 more , Vieira ACF, Costa G, Pires PC, Mazzola PG, Veiga F, Ferreira L, Paiva-Santos AC
Drug Deliv Transl Res · 2026 Feb · PMID 41299111 · Publisher ↗
Traditional topical therapies can have considerable side effects, leading to the research for natural and biocompatible alternatives. Ectoine, a natural osmolyte produced by extremophilic microorganisms, possesses an ext...
Traditional topical therapies can have considerable side effects, leading to the research for natural and biocompatible alternatives. Ectoine, a natural osmolyte produced by extremophilic microorganisms, possesses an extraordinary ability to bind water molecules and stabilize membranes, with powerful moisturizing and anti-inflammatory properties, which makes it a multifunctional and valuable molecule for topical applications. Pre-clinical and clinical data confirm that ectoine-based creams increase skin moisture, improve the skin's barrier function, and reduce inflammation, effectively alleviating the symptoms of atopic dermatitis. In addition, ectoine can be used in nasal sprays, providing substantial relief from the symptoms of rhinosinusitis, such as nasal congestion and irritation of the mucous membranes, without the adverse effects associated with the usual decongestants. In ophthalmic formulations, ectoine-containing eye drops moisturize, stabilize the tear film, and relieve irritation and itching, making them a viable option for the ocular symptoms of allergic conjunctivitis and the long-term treatment of dry eye disease. Therefore, ectoine is crucial in developing treatments that improve patients' quality of life by offering a safer alternative to conventional therapies.Briefly, this review aims to explore the topical applications, characteristics, and mechanisms of action of ectoine, focusing on its efficacy and safety in the treatment of atopic dermatitis, rhinosinusitis, rhinitis sicca, dry eye disease, and allergic conjunctivitis. Moreover, biotechnological methods for producing ectoine are outlined, highlighting advances in microbial synthesis and process optimization for more sustainable technology, as well as showing ectoine-containing products and their position on the market.
Comparative review of translational approaches in lipid-based and water-based encapsulation strategies for coenzyme Q10.
Mohamad Sukri N, Abd Rahim N, El Enshasy HA … +6 more , Aman Nor NF, Wan Azelee NI, Md Salleh L, Kamari ZH, Sujani S, Abdul Manas NH
Drug Deliv Transl Res · 2026 Feb · PMID 41284153 · Publisher ↗
The global coenzyme Q10 (CoQ10) market is expanding, driven by the increasing prevalence of chronic diseases, particularly cardiovascular disorders. Forecasts project a compound annual growth rate of 9.68% from 2025 to 2...
The global coenzyme Q10 (CoQ10) market is expanding, driven by the increasing prevalence of chronic diseases, particularly cardiovascular disorders. Forecasts project a compound annual growth rate of 9.68% from 2025 to 2034. Despite its critical role in cellular energy metabolism and antioxidant defense, CoQ10's clinical potential is constrained by poor water solubility and low oral bioavailability. This review delivers a critical and translational comparison of lipid-based and water-based encapsulation strategies, offering novel insights into their mechanistic advantages, formulation challenges, and clinical applicability for enhanced CoQ10 delivery. Lipid-based systems, such as self-emulsifying drug delivery systems (SEDDS), liposomes, and nanoemulsions, improve solubility and gastrointestinal absorption, protect CoQ10 from degradation, and promote lymphatic transport. However, they often require high excipient content and exhibit stability concerns, such as susceptibility to oxidation. Water-based approaches, including β-cyclodextrin complexation, polymeric nanoparticles, solid dispersions, and CoQ10-nicotinamide cocrystals, enhance aqueous solubility and absorption while offering better chemical stability and lower formulation cost. This review highlights the mechanistic differences, benefits, and limitations of each strategy, providing critical insights for the rational design of CoQ10 delivery systems. The findings support formulation optimization to improve therapeutic efficacy and inform manufacturing decisions for clinical and commercial applications. Looking ahead, future directions may include nano-enabled personalized medicine strategies based on individual metabolic profiles and the development of intranasal CoQ10 delivery platforms that leverage nanoscale lipid or water-based carriers for direct nose-to-brain transport in neurological disease therapy.
Combining Leu-enkephalin nanomedicines with enkephalinase inhibitors: a promising painkiller strategy?
Prades L, Hazam H, Gobeaux F … +8 more , Yesylevskyy S, Ramseyer C, Ranieri L, Loukil S, Cailleau C, Sitbon P, Couvreur P, Lepetre-Mouelhi S
Drug Deliv Transl Res · 2026 Jul · PMID 41284152 · Publisher ↗
This study investigates the potential of a novel nanomedicine approach relying on squalene nanoparticles of endogenous enkephalinase inhibitors (EEI) - opiorphin (OPN) and STR-324 - to alleviate pain by potentiating the...
This study investigates the potential of a novel nanomedicine approach relying on squalene nanoparticles of endogenous enkephalinase inhibitors (EEI) - opiorphin (OPN) and STR-324 - to alleviate pain by potentiating the action of enkephalins in vivo, in a model of acute inflammatory pain. A library of squalene-based EEI prodrugs was synthesized. These prodrugs were unable to self-assemble into nanoparticles, in contrast to the other squalenoylated prodrugs, probably due to their high hydrophilicity. By incorporating either squalenic acid (SQ) or enkephalin-squalene (LENK-SQ) prodrug as adjuvants with strong self-assembling properties, we successfully formulated nanoparticles of STR- or OPN-SQ (EEI-SQ NPs) and performed their physicochemical characterization. The analgesic efficacy of these formulations was evaluated in a carrageenan-induced pain model using the Hargreaves test to assess hyperalgesia. Nevertheless, the intravenous administration of EEI-SQ NPs caused systemic toxicity which was investigated through in vitro incubation assays. It was discovered that EEI-SQ bioconjugates exhibited strong interactions with divalent anions in physiological media, leading to nanoparticles aggregation, which was further confirmed in silico by molecular dynamics simulations. EEI-SQ NPs administered subcutaneously successfully enhanced the anti-hyperalgesic effect of LENK-SQ NPs. However, it was considered as not relevant enough regarding the observed local toxicity.
Functional polysaccharide-based bioactive delivery systems for urinary and reproductive system therapeutics.
Lin YW, Rethi L, Pan WY … +2 more , Nguyen HT, Chuang AE
Drug Deliv Transl Res · 2025 Nov · PMID 41254280 · Publisher ↗
Damage to lower genitourinary (GU) organs, which can lead to organ dysfunction and/or infertility, poses a significant threat to individual health and quality of life. Polysaccharide-based delivery systems for biological...
Damage to lower genitourinary (GU) organs, which can lead to organ dysfunction and/or infertility, poses a significant threat to individual health and quality of life. Polysaccharide-based delivery systems for biologically active therapeutics have emerged as promising strategies for regenerative treatment. However, several challenges remain in achieving site-specific delivery with optimal bioactivity, stability, and sustained release for long-term therapeutic efficacy.This review highlights recent advancements in delivery system design, including manufacturing technologies, bioactive loading strategies, and innovative therapeutic applications aimed at enhancing clinical outcomes. We explore how these developments are being applied to regenerative therapies targeting lower GU injuries and dysfunctions.Notably, the integration of smart delivery technologies, tailored biomaterials, and bio responsive platforms has led to the development of more precise, multifunctional, and intelligent systems. Encouraging results have been reported both in clinical applications and preclinical in vivo models. Furthermore, the continuous evolution of biomedical materials, therapeutic agents, and 3D printing techniques, combined with emerging engineering approaches, offers a promising future for the management and repair of lower GU tract disorders.
Formulation and evaluation of probucol-LCA nanoparticles for supressing oxidative stress-related retinal degeneration.
Wagle SR, Brunet A, James R … +10 more , Sen LY, Lorenzo MM, Kovacevic B, Diress M, Foster T, Ionescu CM, Lim P, Carvalho LS, Mooranian A, Al-Salami H
Drug Deliv Transl Res · 2026 Apr · PMID 41254279 · Publisher ↗
Retinal degenerative diseases are a major cause of vision loss worldwide, with oxidative stress being a key pathological driver. This study aimed to develop and evaluate probucol-lithocholic acid (LCA) nanoparticles for...
Retinal degenerative diseases are a major cause of vision loss worldwide, with oxidative stress being a key pathological driver. This study aimed to develop and evaluate probucol-lithocholic acid (LCA) nanoparticles for targeted retinal protection. Nanoparticles were formulated via spray drying of a mixture containing probucol, low-viscosity sodium alginate, polyethylene glycol, and LCA, followed by detailed physicochemical characterization. In vitro studies using human retinal pigment epithelial (ARPE-19) cells exposed to oxidative (H₂O₂) and hyperglycaemic stress demonstrated that the probucol-LCA nanoparticles significantly improved cell viability, reduced reactive oxygen species (ROS), restored glutathione (GSH) levels, and enhanced mitochondrial bioenergetics compared with non-functionalized formulations. In vivo, a single intravitreal injection of the nanoparticles in wild-type and retinal degeneration 1 (rd1) mice confirmed their biocompatibility and safety, showing no adverse effects on retinal structure or function. These findings establish the probucol-LCA nanoparticle system as a safe and effective antioxidant platform for intravitreal delivery. Its demonstrated in vitro efficacy and favourable safety profile highlight its potential for translation into therapeutic interventions for oxidative stress related retinal diseases.
Dual drug co-encapsulation into liposomes and liposome-derived nanosystems for improved synergistic treatment of skin diseases.
Rodrigues S, Veiga F, Paiva-Santos AC … +1 more , Pires PC
Drug Deliv Transl Res · 2026 Feb · PMID 41247420 · Publisher ↗
Skin disorders impact nearly one-third of the global population, and represent the fourth most common cause of human diseases. However, delivering drugs into and through the skin is a significant challenge due to its low...
Skin disorders impact nearly one-third of the global population, and represent the fourth most common cause of human diseases. However, delivering drugs into and through the skin is a significant challenge due to its low permeability, which severely limits the efficacy of conventional topical and transdermal formulations. To tackle this issue, liposomes and liposome-derived nanosystems can be of use, which, among other advantages, also have the capacity to encapsulate more than one drug molecule simultaneously, allowing combination therapy. This review provides a comprehensive summary and critical analysis of recent studies regarding dual drug co-encapsulation into liposomes and liposome-derived nanosystems as an improved therapeutic approach for the treatment of several skin diseases, such as acne vulgaris, androgenetic alopecia, cutaneous leishmaniasis, psoriasis, vitiligo, and chronic wounds, and for dermal analgesia and general skin oxidative stress management purposes. Conventional and modified liposomes, niosomes, transfersomes, ethosomes, invasomes, cerosomes, liposomal gels, and niosomal gels were developed, co-encapsulating synthetic and nature-derived substances such as adapalene, amphotericin B, benzoyl peroxide, bicalutamide, bupivacaine, buprenorphine, curcumin, ginger, glycyrrhetinic acid, metformin, methotrexate, microRNA-21, minoxidil, nicotinamide, Nigella sativa seed oil, pentamidine, psoralen, resveratrol, simvastatin, tocopherol acetate, tretinoin, and virgin coconut oil. By co-encapsulating active substances with distinct mechanisms of action, the developed nanosystems provide synergistic therapeutic effects, leading to reduced toxicity and enhanced bioavailability, potentially resulting in improved clinical outcomes, and presenting a promising alternative to conventional treatments. Through addressing clinical and regulatory framework aspects, these innovative therapies might one day transition from bench to market to improve the patient's quality-of-life.
CEB-01 membrane loaded with SN-38 for local post-resection control and metastasis reduction in preclinical pancreatic cancer models.
Ninou AH, Caruana P, Marti L … +9 more , Tornero J, de Llanos EL, Casas FC, De la Fuente N, Aguilar-Del Castillo F, García-Sanchez C, Cepeda-Franco C, Padillo-Ruíz J, Céspedes MV
Drug Deliv Transl Res · 2025 Nov · PMID 41225246 · Publisher ↗
Pancreatic cancer (PC) is an aggressive malignancy with extremely poor prognosis, in which resection surgery remains the only therapeutic option with curative intent. Patients often present with locoregional metastases i...
Pancreatic cancer (PC) is an aggressive malignancy with extremely poor prognosis, in which resection surgery remains the only therapeutic option with curative intent. Patients often present with locoregional metastases in lymph nodes, peritoneum and liver at diagnosis (~ 50-60% of patients), precluding the possibility of surgical resection. In addition, majority of patients develop tumor recurrence after surgery, which can be local or metastatic, in both cases negatively affecting survival outcomes. Irinotecan has proven effective as an adjuvant setting after surgery and currently used in chemotherapeutic combination regimes for the management of PC. The extreme low solubility of irinotecan's active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), along with its instability at physiological pH, creates significant challenges for SN-38 systemic administration as a free drug, despite its much greater potency compared to irinotecan. CEB-01 is a novel formulation of SN-38 in the form of a biodegradable nanofiber Poly (Lactic-co-Glycolic Acid) (PLGA) membrane. Implanted in the PC surgical bed, CEB-01 releases SN-38 in a prolonged manner for tumor growth control.Using in vivo pancreatic models, CEB-01 shows statistically significant reduction of postoperative tumor growth at local concentrations of SN-38 between 25 and 50 µg/cm, both as monotherapy and in combination with chemotherapy (5-FU 30 mg/kg and 90 mg/kg leucovorin), in MIA PaCa-2 and metastatic Panc-1 pancreatic xenograft models. In addition, CEB-01 shows statistically significant effect on metastatic control, by reducing the number of metastases in liver, lymph nodes, and peritoneum in treated animals. Overall, no systemic toxic effects or changes in body weight were observed, confirming that CEB-01 shows a tolerable profile after post-surgical resection in in vivo models of PC. In conclusion, CEB-01 is a feasible drug delivery strategy for the local release of SN-38 as an add-on adjuvant to current PC treatments, strategy that could potentially reduce systemic side effects compared to intravenous administration of irinotecan.
Development, in silico, in vitro, and in vivo evaluation of gatiserts: HME-based ophthalmic inserts for prolonged ocular delivery of gatifloxacin.
Sharma A, Behera SK, Singh J … +6 more , Beladiya J, Sheth D, Rana D, Borah S, Jain A, Benival D
Drug Deliv Transl Res · 2026 Apr · PMID 41225245 · Publisher ↗
The objective of this study was to develop and characterize hot-melt extrusion (HME)-based gatifloxacin-loaded ophthalmic inserts (Gatiserts) to enhance ocular retention and reduce dosing frequency for bacterial conjunct...
The objective of this study was to develop and characterize hot-melt extrusion (HME)-based gatifloxacin-loaded ophthalmic inserts (Gatiserts) to enhance ocular retention and reduce dosing frequency for bacterial conjunctivitis management. Gatiserts were formulated using hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and Poloxamer 407 via HME, ensuring uniform drug-polymer distribution. CaliCut technology enabled precise cutting, achieving consistent insert dimensions. Physicochemical characterization included XRD, DSC, ATR-FTIR, and SEM/EDS. In vitro drug release and kinetic modeling were performed, while molecular dynamics simulations assessed polymer-mucin interactions (MUC-1, MUC-4, MUC-16) to predict mucoadhesion. In vitro, antimicrobial activity against Staphylococcus aureus and Escherichia coli was performed, and in vivo, ocular irritation studies were conducted in rabbits. The optimized formulation (F10) exhibited well-defined dimensions (1.27 mm diameter, 3.5 mm length) with uniform drug distribution, attributed to HME and CaliCut precision. In vitro studies demonstrated sustained drug release (82.07% over 9 h), following Peppas-Sahlin kinetics (R² = 0.9874). Molecular simulations indicated strong polymer-mucin interactions (docking scores: -9.7 to -10.3 kcal/mol), suggesting enhanced mucoadhesion. XRD and DSC confirmed amorphous drug dispersion, while ATR-FTIR and SEM/EDS validated chemical stability and homogeneous drug distribution, respectively. In vitro, antimicrobial studies showed potent inhibition of S. aureus and E. coli over 24 h. Gatiserts exhibited excellent biocompatibility (Draize score: 0) with no ocular irritation. The prolonged drug release, enhanced mucoadhesion, and excellent biocompatibility of Gatiserts suggest their potential for a significantly reduced dosing frequency compared to conventional eye drops, addressing rapid precorneal clearance and improving patient compliance in bacterial conjunctivitis management.
Development and evaluation of recombinant Varicella-Zoster virus glycoprotein E protein microneedles for enhanced pediatric vaccine delivery.
Lee DE, Cha HR, Lee YL … +9 more , Chung HW, Park S, Oh YJ, Jung E, Baek SK, Ahn BC, Yum JS, Lee JM, Park JH
Drug Deliv Transl Res · 2025 Nov · PMID 41217681 · Publisher ↗
Varicella-zoster virus (VZV) infection remains a significant pediatric health concern, and current live-attenuated vaccines are limited by cold-chain requirements, reactivation risk, and injection-related anxiety. To add...
Varicella-zoster virus (VZV) infection remains a significant pediatric health concern, and current live-attenuated vaccines are limited by cold-chain requirements, reactivation risk, and injection-related anxiety. To address these challenges, we developed and evaluated two recombinant VZV glycoprotein E (gE) microneedle (MN) platforms-coated microneedles (gE C-MN) and powder-attached microneedles (gE P-MN)-for painless, skin-targeted pediatric vaccination.Immunogenicity assessments in boosted BALB/c mice revealed comparable IgG antibody titers (> 15 log₂) induced by gE P-MN, gE C-MN, and traditional intramuscular injection, indicating equivalent efficacy among delivery methods. Both MN formulation maintained antigen integrity during fabrication and exhibited excellent long-term stability at 25 °C over 12 months, with gE P-MN showing slightly superior stability compared to gE C-MN. Notably, both MN types significantly outperformed a liquid vaccine formulation in stability. Ex vivo porcine skin studies confirmed high intradermal delivery efficiency (> 95%) for both microneedle types. Additionally, both platforms demonstrated no skin irritation or pyrogenic effects in rabbit safety models.These findings demonstrate that powder-attached and coated microneedles effectively deliver recombinant VZV gE vaccines, satisfying essential requirements for pediatric immunization, including immunogenicity, storage stability, and safety. Thus, recombinant VZV gE microneedles represent a promising, user-friendly vaccine platform capable of enhancing compliance and vaccine accessibility, particularly in resource-limited regions..
Novel voriconazole-loaded hyalurosomes optimized for enhanced skin penetration and antifungal activity against Candida albicans.
Nácher A, Peris JE, Taléns-Visconti R … +4 more , Díez-Sales O, Manca ML, Manconi M, Usach I
Drug Deliv Transl Res · 2026 Jun · PMID 41214392 · Full text
Cutaneous candidiasis, mainly caused by Candida albicans, is a growing global health concern and is listed by WHO as a high-priority fungal threat. Suboptimal penetration of conventional vehicles limits the efficacy of c...
Cutaneous candidiasis, mainly caused by Candida albicans, is a growing global health concern and is listed by WHO as a high-priority fungal threat. Suboptimal penetration of conventional vehicles limits the efficacy of current topical antifungals, increasing the risk of severe and invasive infections. Therefore, there is an innovative research field in advanced topical delivery systems to improve drug deposition, retention and antifungal efficacy. The main objective of this work was to develop nanocarriers based on hyalurosomes for the delivery of voriconazole (VCZ) and evaluate their potential to enhance the drug's cutaneous penetration and antifungal activity. Four VCZ-loaded hyalurosomal formulations were prepared (H1-H4) by modulating the proportions of phospholipid and polyols. Although changes in some physicochemical properties were observed, all the VCZ-loaded nanosystems were nanosized (< 140 nm), spherical, multilamellar and exhibited high entrapments efficiencies (> 72%), excellent biocompatibility with human keratinocytes and potent antifungal activity against C. albicans. VCZ release from formulation H1 (1% phospholipid, 10% ethanol) followed a Fickian mechanism, while H2-H4 (4-10% phospholipid, 2.5-10% ethanol) exhibited anomalous diffusion involving both diffusion and matrix relaxation or erosion. Additionally, H1 and H2 (1-4% of phospholipid, 10% ethanol) achieved significantly enhanced drug penetration into deeper skin layers and superior in vivo antifungal efficacy compared to VCZ dispersion. The results highlight the potential of hyalurosomes as a next-generation topical antifungal delivery system, effective against both superficial and invasive candidiasis, with formulations H1 and H2 emerging as the most promising candidates for the treatment of the more invasive forms.
Design and preparation of novel domperidone loaded polymeric blend electrospun nanofibers for improved oral pharmacodynamic activity.
Shatla K, Sweed E, Eltokhy S … +5 more , Abdel-Rahman A, Ismail AH, El-Sattar NA, Kenawy ER, Haggag Y
Drug Deliv Transl Res · 2026 Jun · PMID 41199000 · Full text
Domperidone (DOM) is a BCS class II drug which widely used as an oral medication for the control of nausea and vomiting. It showed a very low and variable bioavailability related to its very poor solubility and pre-syste...
Domperidone (DOM) is a BCS class II drug which widely used as an oral medication for the control of nausea and vomiting. It showed a very low and variable bioavailability related to its very poor solubility and pre-systemic metabolism. Polymeric nanofibers (PNFs) exhibit unique properties that make them a favorable choice for drug delivery applications. The study aimed to develop an optimum fast-dissolving oral polymeric electrospun nanofiber of DOM using Eudragit L100/Polyvinyl alcohol (EL-100/PVA) polymer blend. The fabrication process was optimized through a set of formulation parameters (composition of the polymer blend, polymer blend concentration, and electrospinning voltage). The DOM-loaded EL-100/PVA NFs were characterized for surface shape, nanosize, % drug loading, DOM in vitro release, drug/polymer interaction, and in vivo prokinetic study. The optimization process showed defect-free DOM-loaded NFs with very low nano diameter, high DOM loading, and superior in vitro dissolution of DOM at intestinal pH (about 90% of the drug released within 5 min). The drug/polymer interaction study demonstrated the conversion of DOM into an amorphous form, which facilitated its dissolution. No physicochemical interaction between DOM and the polymer blend was observed. In vivo prokinetic study signified the orally enhanced prokinetic activity of DOM-loaded NF relative to pure DOM and commercial DOM product. The DOM-loaded EL-100/PVA NFs exhibited a better effect on the gastrointestinal reactivity relative to free DOM and commercial DOM product. The superior in vitro dissolution and in vivo prokinetic activity proved the promising potential of polymeric NFs to improve the oral delivery of DOM. The optimized DOM-loaded EL-100/PVA NFs may allow for dose reduction and low cardiovascular risk compared to conventional DOM tablets.
Surface decoration of solid lipid nanoparticles with cyclic RGD peptides for precision therapy in high-risk neuroblastoma.
Lorenzoni S, Aydillo C, Rodríguez-Nogales C … +1 more , Blanco-Prieto MJ
Drug Deliv Transl Res · 2026 Jul · PMID 41196511 · Full text
High-risk neuroblastoma poses significant therapeutic challenges due to tumor heterogeneity, drug resistance, and systemic toxicity associated with conventional chemotherapies. To overcome these limitations, we developed...
High-risk neuroblastoma poses significant therapeutic challenges due to tumor heterogeneity, drug resistance, and systemic toxicity associated with conventional chemotherapies. To overcome these limitations, we developed cyclic RGD-decorated solid lipid nanoparticles for integrin-targeted delivery of etoposide, aiming to enhance tumor selectivity and therapeutic efficacy. SLNs were prepared using hot homogenization and ultrasonication, with cyclic RGD peptides conjugated to the surface via non-covalent and covalent strategies. Among three conjugation approaches evaluated, maleimide-based functionalization was selected for its reproducibility, stability, and high coupling efficiency. RGD-functionalized SLNs were physicochemically characterized and assessed for integrin-mediated uptake, cytotoxicity, cell cycle effects, and apoptosis induction in SH-SY5Y (integrin-high) and SK-N-BE(2) (integrin-low) NB cell lines. RGD-SLNs demonstrated efficient peptide conjugation while maintaining colloidal stability and drug loading. Flow cytometry confirmed enhanced uptake in αvβ3 integrin-expressing SH-SY5Y cells, with moderate uptake in SK-N-BE(2) cells. ETP encapsulation within SLNs significantly improved its cytotoxic profile, with RGD functionalization further reducing IC values and promoting apoptosis. These findings establish RGD-functionalized SLNs as a promising integrin-targeted platform for ETP delivery in NB. To our knowledge, this is the first report of this approach using SLNs for NB, offering a novel strategy for translational nanomedicine.
Optimization of print parameters for batch and continuous manufacturing of three-dimensional (3D) printed dosage forms using artificial intelligence and machine learning.
Chitnis K, Lu Y, Rhoads B … +3 more , Chakka LRJ, Choudhury S, Maniruzzaman M
Drug Deliv Transl Res · 2026 Jun · PMID 41188561 · Full text
Three-dimensional printing (3DP) holds significant potential for developing personalized pharmaceutical oral dosage forms (printlets). 3D printing has the advantage of fabricating complex geometric structures for versati...
Three-dimensional printing (3DP) holds significant potential for developing personalized pharmaceutical oral dosage forms (printlets). 3D printing has the advantage of fabricating complex geometric structures for versatile drug release profiles, enhancing patient preference, palatability and swallowability, reducing the pill burden, and increasing dose accuracy. Optimizing printing parameters is crucial in determining the quality of the printlets during dosage development. The integration of machine learning (ML) can reduce production costs and time through parameter optimization based on trained datasets. This research is focused on optimizing parameters for fused deposition modeling (FDM) based batch and continuous printing methods. The algorithm was trained using a three-level full factorial design, which generated data in the form of printlets with different parameters. Both defect and defect-free printlets were analyzed using image segmentation. Machine learning tools including Gaussian Process Regressor (GPR) and Efficient Global Optimization (EGO) were used to predict and select processing parameters for a targeted percentage surface defect. The final trained algorithm predicted new parameter sets for both batch (R-0.8783) and continuous (R-0.9364) printing methods to achieve zero defects, and the same was confirmed through printing and characterization of printlets which showed no defects. The algorithm was later adapted successfully to a variety of materials within the temperature range of 190-220 ℃ and predicted zero-defect printlets. Scanning electron microscopy (SEM) revealed the absence of defects on the surfaces of the materials. Results showed that flow rate (110 and 120 mm/s) had a significant impact on printlet quality withwithout defects for both batch and continuous printing, compared to print speed, print temperature, and infill density. This research provides new insights into the development of optimized FDM printlets using batch and continuous printing with adaptive machine learning for pharmaceutical dosage manufacturing.
Biodegradable microneedles for transdermal sitagliptin delivery: in vivo insights into enhanced diabetes management.
Yehia RM, Ossama M, Elosaily GH … +3 more , Fayez AM, Amer RI, Attia DA
Drug Deliv Transl Res · 2026 Jun · PMID 41182669 · Full text
Microneedles (MNs) offer a promising alternative for transdermal delivery of hydrophilic drugs such as sitagliptin, evading the gastrointestinal side effects associated with oral administration. Thus, the study focuses o...
Microneedles (MNs) offer a promising alternative for transdermal delivery of hydrophilic drugs such as sitagliptin, evading the gastrointestinal side effects associated with oral administration. Thus, the study focuses on the transdermal delivery of sitagliptin, an antidiabetic drug that inhibits dipeptidyl peptidase-4 (DPP-4). The research includes the formulation and in-vitro, ex-vivo, and in-vivo characterization of MNs for sitagliptin delivery. MN molds were fabricated using Stereolithography (3D Printing), and biocompatible MNs were made from hyaluronic acid (HA), chitosan, polyvinylpyrrolidone and polyvinyl alcohol (PVA). Sitagliptin MNs with PVA (SMP) and HA (SMH) exhibited favorable physical and mechanical properties, with drug content of 3.5 ± 0.14 mg/g and 3.8 ± 0.12 mg/g, respectively. SMH showed superior skin penetration due to sharper, stiffer tips. Ex-vivo studies using rat skin indicated that the SMH yielded a higher cumulative permeation (36.58%) compared to SMP (24.04%). Additionally, sitagliptin primarily accumulated in the epidermis, with approximately 56% for SMH and 50% for SMP. In-vivo results demonstrated that both SMP and SMH effectively lowered fasting blood glucose levels, with SMH notably improving postprandial glucose and insulin levels. Overall, HA-based biodegradable microneedles present a promising, minimally invasive strategy for sitagliptin delivery, enabling effective type 2 diabetes management while avoiding its gastrointestinal side effects.
Dynamic 3D microfluidic platform for exploring combined targeted therapy, chemotherapy, and virotherapy delivery in ovarian cancer.
Kuryk L, Mathlouthi S, Casagrande L … +6 more , Pesce C, Tognetti F, Malfanti A, Masny A, Caliceti P, Garofalo M
Drug Deliv Transl Res · 2025 Nov · PMID 41182668 · Publisher ↗
Ovarian cancer poses a persistent therapeutic challenge due to late-stage diagnosis, frequent relapse, and resistance to standard therapies. While oncolytic viruses (OVs) offer a promising immunotherapeutic approach, the...
Ovarian cancer poses a persistent therapeutic challenge due to late-stage diagnosis, frequent relapse, and resistance to standard therapies. While oncolytic viruses (OVs) offer a promising immunotherapeutic approach, their clinical efficacy remains limited by an immunosuppressive tumor microenvironment (TME) and inefficient delivery. To address these barriers, we developed a dynamic microfluidic-based 3D ex vivo tumor model to evaluate a systemic, multimodal treatment strategy in ovarian cancer. The model incorporates perfusable tumor spheroids cocultured with peripheral blood mononuclear cells (PBMCs) and endothelial cells (HUVECs), enabling the simulation of vascularized tumor environments and systemic drug perfusion. All therapeutic agents-including the oncolytic adenovirus Ad5/3-D24-ICOSL-CD40L, cisplatin, paclitaxel, and nintedanib-were administered through flow-based circulation to more accurately replicate human pharmacokinetic conditions and tumor-drug interactions. Our results demonstrated that a priming regimen-where Ad5/3-D24-ICOSL-CD40L was administered 48 h before chemotherapy-significantly outperformed the co-administration strategy, reducing spheroid areas and mitigating tumor rebound. Enhanced therapeutic response was associated with increased viral replication, sustained immunogenic cell death, and improved immune cell infiltration, underscoring the importance of sequencing and microenvironment preconditioning. This tumor-on-a-chip platform provides a physiologically relevant tool for real-time monitoring of treatment response, immune activation, and drug delivery under continuous flow. By bridging the gap between traditional in vitro models and in vivo studies, it offers a powerful preclinical system for optimizing combination regimens and advancing personalized therapies in ovarian cancer.
Leveraging quantum chemical properties in transfer learning for predicting blood-brain barrier permeability of drugs.
Lim MA, Yonk MG, Hoang KB … +6 more , Molinaro AM, Raj M, Du Y, Boulis NM, Hassaneen W, Lei K
Drug Deliv Transl Res · 2026 Jun · PMID 41160380 · Full text
The blood-brain barrier (BBB), crucial for central nervous system (CNS) homeostasis, poses challenges for drug delivery in CNS diseases due to selective permeability. Because of this difficulty, there are limited treatme...
The blood-brain barrier (BBB), crucial for central nervous system (CNS) homeostasis, poses challenges for drug delivery in CNS diseases due to selective permeability. Because of this difficulty, there are limited treatments developed for CNS diseases. As a solution, computational models can be implemented in treatment development to enable rapid screening of drug permeability, saving time and resources. This study explores machine learning, deep learning, and transfer learning models to predict the BBB permeability of drug molecules, validated through an in vitro assay known as Parallel Artificial Membrane Permeability Assay-BBB (PAMPA-BBB). Using the Blood-Brain Barrier Database (B3DB) of ∼ 8,000 compounds of known BBB permeability, classification models including support vector machines (SVMs), deep neural networks (DNNs), direct message passing neural networks (D-MPNNs), and transfer learning with quantum chemical properties were developed. Experimental validation with 18 compounds from the Emory Enriched Bioactive Library (EEBL), a library containing 1,018 FDA-approved pharmacologically active compounds of known activity, highlighted PAMPA-BBB as a robust validation method. The SVM model with combined 2D RDKit and Morgan fingerprint molecular representation achieved high performance (accuracy: 89.08%) on the B3DB test set. The best-performing models for the 18 EEBL compounds were transfer learning models. In particular, the model trained on the QM9-extended polarizability property correctly classified 17 out of 18 compounds, while the model trained on the QM9-extended dipole moment property achieved correct classification across all 18 experimental compounds. Additional analyses demonstrated that QC-based transfer learning provides complementary predictive value beyond traditional molecular descriptors such as LogP and molecular weight. QC-pretrained models achieved higher accuracy and ROC-AUC on both the B3DB and external PAMPA test sets, with performance remaining robust even after descriptor ablation. Moreover, QC-pretrained models outperformed the baseline of P-glycoprotein (P-gp) inhibition, underscoring the unique contribution of quantum-derived representations to BBB permeability prediction. Therefore, this study motivates the synergy of computational and experimental methods in enabling faster, more cost-effective, and targeted identification of CNS-active or CNS-sparing drugs.
Thermosensitive in situ gel powered by pectin-chitosan nanocapsules for intraocular delivery of acetazolamide: in vitro, ex vivo, and in vivo evaluation.
Bagul U, Khot S, Monde A … +4 more , Ashtekar K, Moni S, Kokare C, Tagalpallewar A
Drug Deliv Transl Res · 2026 Jun · PMID 41136814 · Publisher ↗
The current study aimed at development of acetazolamide loaded pectin-chitosan nanocapsules (APCNC) via a polyelectrolyte complex coacervation technique, further incorporated into a poloxamer 407 and HPMC-based in situ g...
The current study aimed at development of acetazolamide loaded pectin-chitosan nanocapsules (APCNC) via a polyelectrolyte complex coacervation technique, further incorporated into a poloxamer 407 and HPMC-based in situ gel (APCNC-ISG). The resulting APCNC demonstrated a positive zeta potential (+ 23.45 ± 0.30 mV), high entrapment efficiency (94.33 ± 1.2%), small hydrodynamic size (104 ± 2.4 nm), and narrow size distribution (PDI < 0.3). The SEM and TEM analyses confirmed the spherical morphology and nano range size of APCNC, while XRD analysis revealed the conversion of acetazolamide from a crystalline to an amorphous state. The APCNC-ISG exhibited pseudoplastic rheology with a gelling temperature of 36 ± 0.5 °C and rapid gelation within 10 ± 2 s. Furthermore, texture analysis displayed suitable adhesive properties. In vitro drug release and ex vivo permeation studies showed a sustained drug release over an extended period. The HET-CAM test and histopathological evaluation confirmed the non-irritating and non-toxic nature of the formulation, supporting its suitability for ophthalmic use. Pharmacodynamic studies demonstrated that APCNC-ISG significantly reduced intraocular pressure and maintained the effect for a prolonged duration compared to other formulations. These findings suggest that APCNC-ISG is a promising, adaptable, and effective drug delivery system for the treatment of glaucoma.
Local delivery of Doxorubicin and Olaparib loaded injectable hydrogels with adjuvant radiotherapy improves survival in a glioblastoma in vivo model.
Cavanagh R, Shaw G, McCrorie P … +10 more , ElSherbenny A, Pandele A, Jearranaiprepame S, Ghanem B, Allcock N, Wurdak H, Mathew RK, Alexander C, Rahman R, Moloney C
Drug Deliv Transl Res · 2026 Jul · PMID 41131434 · Full text
Local drug delivery systems (LDDS) are a promising method to overcome challenges associated with chemotherapeutic treatment of brain tumours, namely poor blood-brain barrier penetration. Here we report a poly(ethylenegly...
Local drug delivery systems (LDDS) are a promising method to overcome challenges associated with chemotherapeutic treatment of brain tumours, namely poor blood-brain barrier penetration. Here we report a poly(ethyleneglycol)-poly(lactide)-poly(caprolactone)-poly(lactide)-poly(ethyleneglycol) based injectable hydrogel, PELCLE, loaded with Doxorubicin (Dox) and Olaparib (Ola) as an LDDS against glioblastoma (GBM), a primary malignant brain tumour with a poor prognosis. The thermoresponsive properties of the hydrogel, which behaved as a liquid at room temperature and formed a gel at elevated temperatures, were not impacted by the inclusion of chemotherapeutics whereby two-week sustained release was recorded for both Dox and Ola. Drug potency was assessed against a panel of GBM cell lines, both a syngeneic mouse line and primary patient-derived lines, and the combination of Dox/Ola demonstrated synergistic effects at a range of drug: drug ratios. The application of radiotherapy (XRT) in combination with Dox/Ola improved treatment efficacy both in vitro and in vivo, with a significant increase in median survival observed when Dox/Ola PELCLE hydrogels were applied against a surgical resection model of GBM (syngeneic mouse model SB28) with and without the addition of adjuvant XRT (28 and 23 days, respectively, p < 0.01). Furthermore, a long-term survivor was noted in the group treated with the drug loaded HG and XRT, which was associated with a very small residual tumour, indicating the efficacy of this treatment against a GBM in vivo model.
Bioorthogonal liposome-based sequential drug delivery system for enhanced tumor accumulation and targeted therapy.
Wang Y, Zheng W, Yan J … +7 more , Wang L, Pan D, Xu Y, Chen C, Zhou X, Wang X, Yang M
Drug Deliv Transl Res · 2026 Jun · PMID 41129032 · Publisher ↗
Effective drug accumulation at tumor sites remains a critical challenge in cancer therapy due to poor targeting and off-target effects. This study leverages bioorthogonal chemistry to develop a novel liposome-based drug...
Effective drug accumulation at tumor sites remains a critical challenge in cancer therapy due to poor targeting and off-target effects. This study leverages bioorthogonal chemistry to develop a novel liposome-based drug delivery system designed to enhance tumor-specific accumulation and achieve controlled drug release for improved therapeutic outcomes. DBCO- and azide-modified liposomes were engineered to optimize encapsulation efficiency, stability, and sustained drug release. Their performance was evaluated through in vitro cellular assays to assess uptake and toxicity, alongside in vivo biodistribution and efficacy studies in tumor-bearing models. The bioorthogonal liposomes demonstrated significantly enhanced tumor accumulation compared to free doxorubicin and conventional liposomes, achieving a tumor inhibition rate of 60%. In vitro experiments confirmed improved cellular uptake and retention without additional toxicity, while in vivo results highlighted superior therapeutic efficacy and reduced systemic toxicity, as evidenced by increased tumor apoptosis, suppressed proliferation, and minimal body weight loss. This study underscores the potential of bioorthogonal liposomes as a precise drug delivery platform, offering enhanced tumor targeting, better efficacy, and lower toxicity. These findings pave the way for next-generation targeted cancer therapies, with future efforts aimed at refining liposome design for clinical translation.
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