{"title":"Glycerol-based soft vesicular systems for nose to brain delivery of 131I-melatonin: Synthesis, characterization, biodistribution and Pharmacokinetic investigations","authors":"Marwa Eid Sayyed , Shymaa Hatem","doi":"10.1016/j.jddst.2025.107482","DOIUrl":"10.1016/j.jddst.2025.107482","url":null,"abstract":"<div><div>Recently, glycerol has shown several pharmaceutical merits, particularly in intranasal brain delivery. In the present manuscript, advanced glycerol-based soft vesicular systems (glycerosomes, Gs) encompassing melatonin (MLT), a pineal gland hormone, were formulated and characterized in this regard. The prepared vesicles were tested for their particle size (PS), zeta potential (ZP), encapsulation efficiency (EE%) as well as storage stability. Besides, the drug release pattern, surface morphology, viscosity and pH measurements, and permeability through sheep nasal mucosa were conducted on the selected preparations. Bio-distribution along with pharmacokinetic investigations were conducted employing the radioiodinated-MLT (<sup>131</sup>I-MLT) to assess the <em>in-vivo</em> behavior of intravenous solutions (Vs), intranasal solutions (Ns), and intranasal given glycerosomes (NGs). Results revealed that MLT-loaded vesicles showed PS ranging from 202 to 538 nm, negative ZP values varying from −13.10 to −19.26 mV, superior EE% values possessing a range of 84.21–96.53 % and good stability properties manifested by insignificant change in their colloidal properties. In addition, the optimized formulation(s) displayed spherical shape, prolonged drug release reaching ≈100 % throughout 24 h and augmented permeation of approximately 4-fold higher relative to MLT ethanolic solution. The findings of the <em>in-vivo</em> study showed that during the first 5 min, brain/blood ratio (B/B) of NGs was 11.0 and 2.8 times greater compared to Vs and Ns of <sup>131</sup>I-MLT, respectively. Accordingly, the results demonstrated the possibility of employing Gs as a secure and reliable platform for MLT intranasal brain delivery.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107482"},"PeriodicalIF":4.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohsen Poudineh , Movlud Valian , Elmuez A. Dawi , Ayad F. Alkaim , Esmat Aghadavod , Mohammad Javad Azadchehr , Hamed Haddad Kashani , Elahe Seyed Hosseini , Azad Khaledi , Masoud Salavati-Niasari
{"title":"Novel Cu4MgO5 nanoparticles: Investigating anticancer, antibacterial, anti-biofilm, and fimH gene-related biofilm inhibition in Uropathogenic Escherichia coli","authors":"Mohsen Poudineh , Movlud Valian , Elmuez A. Dawi , Ayad F. Alkaim , Esmat Aghadavod , Mohammad Javad Azadchehr , Hamed Haddad Kashani , Elahe Seyed Hosseini , Azad Khaledi , Masoud Salavati-Niasari","doi":"10.1016/j.jddst.2025.107481","DOIUrl":"10.1016/j.jddst.2025.107481","url":null,"abstract":"<div><div><em>Uropathogenic Escherichia coli</em> is the primary cause of urinary tract infections (UTIs). The <em>fimH</em> gene, which encodes an adhesin on type 1 pili, facilitates UPEC colonization and biofilm formation. Due to the high prevalence of UPEC-associated urinary tract infections and the increasing antibiotic resistance related to UPEC, the need for new therapeutic strategies is crucial. This study aimed to design and synthesize novel Cu<sub>4</sub>MgO<sub>5</sub> nanoparticles, investigate anticancer activity, antibacterial and antibiofilm effects, and inhibition of the <em>fimH</em> gene on UPEC. In this study, Cu<sub>4</sub>MgO<sub>5</sub> nanoparticles were synthesized via sol-gel auto-combustion method, and their properties were characterized using XRD, FT-IR, EDX, SEM, TEM, and zeta potential analyses. Characterization showed a pure Cu<sub>4</sub>MgO<sub>5</sub> phase at 700 °C with spherical-like morphology (average size: 172.84 nm) and a zeta potential of −14.9 mV, indicating moderate colloidal stability. Based on results, the nanoparticles showed anticancer activity against HTB-5 bladder cancer cells (IC<sub>50</sub> = 96.33 μg/mL at 24 h; 32.41 μg/mL at 48 h), and low toxicity to HDF normal cells (IC<sub>50</sub> = 1039 μg/mL at 24 h; 624 μg/mL at 48 h). Antibacterial activity of the nanoparticles was assessed by minimum inhibitory concentration (MIC) test and the broth microdilution method. Based on the results, the MIC values of nanoparticles were 7.81–31.25 μg/mL against fifteen clinical isolates of UPEC that were recovered from hospitalized UTI patients and the standard <em>E. coli</em> ATCC 25922 isolate. At sub-MIC concentrations, Cu<sub>4</sub>MgO<sub>5</sub> nanoparticles reduced UPEC biofilm formation by an average of 53 % and downregulated expression of biofilm-associated <em>fimH</em> gene by an average of 72.9 % (a 3.68-fold reduction) in both clinical and standard isolates. These findings demonstrate the potential of novel Cu<sub>4</sub>MgO<sub>5</sub> nanoparticles as a promising therapeutic approach for managing UPEC-associated UTIs by targeting bacterial growth and biofilm formation. However, further <em>in vitro</em> and <em>in vivo</em> studies are necessary.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107481"},"PeriodicalIF":4.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leticia Herminia Higa , Victoria Rebeca Dana González Epelboim , Kajal Ghosal , Ana Paula Perez , Maria Julia Altube , Maria Jose Morilla , Eder Lilia Romero
{"title":"The crying game: lipid-based ophthalmic nanomedicines, and in vitro models to test their performance against dry eye disease","authors":"Leticia Herminia Higa , Victoria Rebeca Dana González Epelboim , Kajal Ghosal , Ana Paula Perez , Maria Julia Altube , Maria Jose Morilla , Eder Lilia Romero","doi":"10.1016/j.jddst.2025.107476","DOIUrl":"10.1016/j.jddst.2025.107476","url":null,"abstract":"<div><div>Dry eye disease (DED), the most prevalent ocular surface disorder worldwide, is currently treated with topical formulations for hydration, lubrication, or anti-inflammatory action. Due to natural barriers of the ocular surface, which limit retention and penetration of exogenous materials, the local bioavailability of topical formulations is minimal. Lipid-based nanomedicines are the most accepted nanomedicines by the pharmaceutical industry and regulatory agencies. Evaporative DED cases could benefit from topical mucoadhesive or mucopenetrating lipid-based ophthalmic nanomedicines (LBON). Besides lubricating and restoring the lipid film, topical nanomedicines offer site-specific drug delivery, magnified targeted intracellular delivery, and reduced systemic drug distribution. The resultant reduced dosing frequency may improve patients' adherence to chronic treatments. To treat DED, however, LBON must not interfere with vision or irritate, and their chemical composition, osmolarity, viscosity, pH, and refractive index must be properly selected/adjusted. Importantly, pharmacokinetics and pharmacodynamics of nanomedicines depend on the techniques used to produce each nanoparticulate structure. Hence, the structural features and resultant activities of nanomedicines prepared at lab scale, differ from those being manufactured at larger industrial scales. Due to ethical and economic reasons, preclinical assessment of LBON should therefore be performed using <em>in vitro</em> disease models. Here, the preclinical performances of LBON reported over the past 10 years, are critically examined. Overall, to become more significant and predictable, further preclinical developments of LBON need to become more technically rigorous and include the help of more sophisticated and broadly available <em>in vitro</em> models.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107476"},"PeriodicalIF":4.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chitosan nano-encapsulation enhances targeted delivery of cecropin-A (1–7)-Melittin peptide to combat intracellular multi-drug-resistant non-typhoidal Salmonella","authors":"Diksha Purushottam Gourkhede , Padikkamannil Abishad , Jess Vergis , Megha Kaore , Vemula Prasastha Ram , Niveditha Pollumahanti , Nitin Vasantrao Kurkure , Satya Veer Singh Malik , Sukhadeo Baliram Barbuddhe , Deepak Bhiwa Rawool","doi":"10.1016/j.jddst.2025.107478","DOIUrl":"10.1016/j.jddst.2025.107478","url":null,"abstract":"<div><div>This study aimed to encapsulate the Cecropin A (1–7)–Melittin (CAMA) peptide within chitosan nanoparticles (CS NPs) and evaluate its antimicrobial activity against multi-drug-resistant (MDR) strains of non-typhoidal <em>Salmonella</em>, employing both <em>in vitro</em> and <em>in vivo</em> assays. The CAMA-loaded CS NPs, synthesized using the ionic gelation technique, exhibited a particle size of 219.31 ± 38.24 nm and a zeta potential of 8.2 ± 0.2 mV, as measured by dynamic light scattering. The encapsulation efficiency was 75.45 ± 2.5 %. Additionally, Fourier-transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy determined the functional groups, morphology and size of the CAMA-loaded CS NPs. The <em>in vitro</em> release kinetics revealed a pH-dependent release profile, with the highest cumulative release observed within 24 h at an alkaline pH (8.20), followed by physiological pH (7.40). Intracellular antimicrobial efficacy was assessed using HEp-2 cell lines, where CAMA-loaded CS NPs effectively cleared intracellular MDR <em>Salmonella</em> strains. Furthermore, CAMA-loaded CS NPs were found to be safe for use with sheep erythrocytes, HEp-2 and RAW 264.7 cell lines, and beneficial gut lactobacilli, and were stable in the presence of proteolytic enzymes and simulated biological fluids. <em>In vivo</em> assays in <em>Galleria mellonella</em> larvae demonstrated an improved survival rate, reduced bacterial count, and minimal cytotoxicity, as confirmed by the lactate dehydrogenase assay. These results correlated with histopathological examination, suggesting that CAMA-loaded CS NPs could be a promising therapeutic candidate for combating intracellular <em>Salmonella</em>.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107478"},"PeriodicalIF":4.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asmaa Ashraf Nemr , Michael M. Farag , Doaa Hegazy , Heba Attia , Eman Abdelhakeem
{"title":"Visionary NanoBoost: Revolutionizing ocular treatment with positively charged Leciplex for enhanced Fenticonazole nitrate ocular delivery","authors":"Asmaa Ashraf Nemr , Michael M. Farag , Doaa Hegazy , Heba Attia , Eman Abdelhakeem","doi":"10.1016/j.jddst.2025.107477","DOIUrl":"10.1016/j.jddst.2025.107477","url":null,"abstract":"<div><div>This work outlines the formulation and characterization of Fenticonazoleloaded LeciPlex (FCN-LPX), adopting a simple blending technique for the eradication of oculomycosis. Fenticonazole nitrate (FCN) is a pleiotropic fungistatic and fungicidal agent with sparse aqueous solubility, hampering its transcorneal permeation. Three independent factors were probed using a 2<sup>3</sup> factorial design (2 blocks, 2 replicates), namely, X<sub>1</sub>: Cationic surfactant type, X<sub>2</sub>: Amount of cationic surfactant (mM), and X<sub>3</sub>: Amount of soybean phosphatidyl choline (mM). The optimized formulation exhibited remarkable entrapment efficiency (82.74 % ± 0.67 %), as verified by DSC and FT-IR analysis. TEM imaging revealed uniformly nanosized vesicles (189.95 ± 2.90 nm) with a robust positive zeta potential (41.35 ± 2.62 mV), which preserved its stability following gamma sterilization and storage. The optimum FCN-LPX demonstrated a bi-phasic release pattern (48.18 % ± 5.65 % at 4 H and 92.85 % ± 6.77 % at 24 H) and notable mucoadhesive properties, ensuring complete drug release. Safety assessments, including pH, surface tension, and refractive index measurements, along with histopathological evaluation, confirmed the formulation's safety profile. Furthermore, FCN-LPX achieved superior <em>ex-vivo</em> transcorneal permeation (3.3-fold) and deeper <em>in-vivo</em> corneal uptake (2.4-fold) compared to conventional FCN suspension. Microbiological analysis highlighted the enhanced antifungal activity of FCN-LPX, evidenced by a larger inhibition zone (11 %), significantly lower minimal inhibitory and fungicidal concentrations (8-fold), as well as improved fungal biofilm inhibition and prolonged antifungal effect. In conclusion, FCN-LPX is a propitious nanoformulation for the effective eradication of persistent oculomycosis.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107477"},"PeriodicalIF":4.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Natural bone-mimicking hydroxyapatite nanoplates as a novel antibiotic drug vehicle: A comparative study with nanorods","authors":"Urvashi Kesarwani , Subham Sekhar Mandal , Pralay Maiti , Ashutosh Kumar Dubey","doi":"10.1016/j.jddst.2025.107474","DOIUrl":"10.1016/j.jddst.2025.107474","url":null,"abstract":"<div><div>Developing a biocompatible drug vehicle with controlled release is vital for safe and sustained antibiotic delivery at infection site to ensure complete bacterial eradication without systemic toxicity. Hydroxyapatite (HA) nanocrystals (NCs), naturally found in living bone as nanoplates (NPTs), offer exceptional biocompatibility and efficient drug binding sites. However, research on antibiotic loading in HA NPTs and their release behavior for controlling bacterial growth is still scarce. Therefore, the present study focuses on antibacterial effect of doxycycline hyclate (DOX)-loaded HA NPTs and thin NPTs (TNPTs) with detailed analyses of their drug loading efficiency and release profile, compared to HA nanorods (NRs). HA NCs, including NRs, NPTs, and TNPTs were synthesized using polyvinyl alcohol (PVA) as a shape-controlling agent via hydrothermal method. The DOX loading efficiencies of HA NRs, NPTs, and TNPTs were determined to be 45.5, 62.2, and 73.3 %, respectively, confirmed using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and electron microscopies. Among the tested HA morphologies, HA TNPTs exhibited the most sustained DOX release profile, followed by HA NPTs and NRs. The differential DOX loading and release rate was explained through surface area of HA and their nature of interaction with DOX. <em>In vitro</em> cell culture studies demonstrated that all DOX-HA NCs effectively promoted cell adhesion, proliferation, and good hemocompatibility. Further, the antibacterial activity of DOX-HA NCs was examined using both, quantitative (MTT assay) and qualitative (Live-dead and colony-counting) experiments against <em>S. aureus</em> bacteria. It is found that unlike free DOX, the prolonged DOX release from HA TNPTs leads to nearly complete inhibition of bacterial growth at 200 μg/ml against the similar bacteria, highlighting their potential as an effective antibiotic vehicle for bacterial eradication.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107474"},"PeriodicalIF":4.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farnaz Maghami , Yalda Samsami , Maryam Haghshenas , Sheyda Zarghami , Parto Tarrah , Fatemeh Suri , Vuk Uskoković , Sina Mozaffari-Jovin , Yahya Sefidbakht
{"title":"Exosome-based drug delivery in cancer therapy: Advances and future perspectives","authors":"Farnaz Maghami , Yalda Samsami , Maryam Haghshenas , Sheyda Zarghami , Parto Tarrah , Fatemeh Suri , Vuk Uskoković , Sina Mozaffari-Jovin , Yahya Sefidbakht","doi":"10.1016/j.jddst.2025.107453","DOIUrl":"10.1016/j.jddst.2025.107453","url":null,"abstract":"<div><div>Despite significant advancements in cancer treatment, the efficacy of chemotherapy and other anti-cancer drugs is often limited by their toxicity and off-target effects. Recent progress in drug delivery systems has led to the development of novel carriers designed to enhance drug efficacy while minimizing toxicity. Among these carriers, exosomes have garnered considerable attention due to their unique properties, including low immunogenicity, high stability, target specificity, and the ability to elicit anti-cancer immune responses. This targeted approach may enhance drug accumulation at tumor sites while reducing systemic toxicity compared to conventional drug delivery methods.</div><div>Despite their therapeutic promise, exosome-based drug delivery faces critical translational barriers, which include limited scalable isolation methods, lack of standardized characterization protocols, and suboptimal drug loading efficiency. Recent bioengineering innovations have achieved improvements in drug loading capacity, while advanced isolation techniques now enable large-scale exosome production. Currently, exosome-based cancer therapeutics are advancing through clinical trials, demonstrating enhanced therapeutic indices and reduced systemic toxicity compared to conventional treatments.</div><div>Exosomes represent transformative precision medicine platforms for cancer therapy, with clinical translation dependent on establishing standardized manufacturing protocols and implementing biomarker-driven patient stratification strategies to optimize therapeutic outcomes.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107453"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shivani Saraf , Ankita Tiwari , Pritish K. Panda , Ankit Jain , Sanjay K. Jain
{"title":"Lineage of lipid-based endosomal escape in cytosolic delivery to cancer: insight into an unprecedented approach","authors":"Shivani Saraf , Ankita Tiwari , Pritish K. Panda , Ankit Jain , Sanjay K. Jain","doi":"10.1016/j.jddst.2025.107458","DOIUrl":"10.1016/j.jddst.2025.107458","url":null,"abstract":"<div><div>Endosomal sequestration of lipid-based systems constitutes a significant limitation that undermines the efficient intracellular delivery of therapeutics in cancer treatment. Upon administration, the intracellular fate of drug or gene constructs within lipid-based delivery systems is influenced by various factors, including p-glycoprotein-mediated efflux and lysosomal degradation, which impede sufficient therapeutic agents from reaching their intended targets. This review exhaustively discusses lipids (properties of lipids and role of pKa) and various lipid-based delivery systems facilitating the endosomal escape for cancer treatment. All aspects, such as endosomal sequestration, methods to promote endosomal escape, a mechanistic overview of endosomal escape, detection of endosomal escape, the application potential of lipid-based systems for cancer treatment, and safety of lipid-based systems, were covered in this manuscript. Existing reviews on endosomal escape have accounted for the various mechanisms,. Still, this review paper also furnishes the role of pKa and applications of molecular dynamic simulation in lipid-based drug delivery, and safety concernsof lipid-based nanosystems. This review discussed the influence of material properties on the endosomal escape of therapeutic agents.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107458"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tailoring lactose particles with various porosities for N-Acetylcysteine delivery to the lungs using porogens and templating agents","authors":"Shohreh Alipour , Reza Tahmasebi , MirAhmad Mazloomi , Hamed Hamishehkar , Ali Nokhodchi","doi":"10.1016/j.jddst.2025.107472","DOIUrl":"10.1016/j.jddst.2025.107472","url":null,"abstract":"<div><div>Creating porous lactose with a low density and a large surface area is an attractive carrier, especially for inhalation therapy, as it can load drugs in pores as well as on its surface, thereby enhancing its aerosolization performance. Porogens and templating agents are common pore-forming techniques that can be employed to create porous materials. N-acetylcysteine (NAC) is an effective mucolytic with anti-inflammatory and antioxidant properties for cystic fibrosis and idiopathic pulmonary fibrosis treatment, which was selected as a drug in the current study. Due to its gastrointestinal side effects and patient compliance, its oral administration is not ideal. Therefore, the current study developed DPI formulations containing porous lactose generated through pore-forming techniques. To this end, the present study compares the effects of ammonium bicarbonate as a porogen and citric acid/boric acid as templating agents on spray-dried porous lactose properties, including density, angle of repose, and yield percentage. Specific surface area study showed the highest surface area of 19 m<sup>2</sup>/g for lactose sample produced via the addition of 10 % ammonium bicarbonate and the smallest surface area (1.4 m<sup>2</sup>/g) was obtained for lactose sample with the addition of 1 % boric acid/2 % citric acid to spray the spray-dried solution. These samples showed about 59 % and 54 % crystallinity, respectively. Aerosolization properties of lactose powder with the highest surface area containing NAC showed a mass median aerodynamic diameter of 3.5 μm with a geometric standard deviation of 3.9, whereas these values for the least surface area powder were 2.4 μm and 4.2. The results showed fine particle fractions of 11 and 18 %, for DPI formulations containing the highest and lowest surface lactose powder, respectively. Results indicated that both pore-forming agents were capable of producing lactose particles with various porosities to obtain different aerosolization performances.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107472"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exogenous cargo-loaded extracellular vesicles as therapeutics: A review of pre-clinical studies","authors":"Jasmine Liberata Fernandes , Dinesh Upadhya , Madhavan Nampoothiri , Shaila Angela Lewis","doi":"10.1016/j.jddst.2025.107473","DOIUrl":"10.1016/j.jddst.2025.107473","url":null,"abstract":"<div><div>Once cast aside and overlooked, extracellular vesicles (EVs) were long believed to be mere vesicles carrying cellular waste. Although identified four decades ago, only in recent years have EVs gained global recognition for their potential as innovative therapeutic and diagnostic agents. These natural lipid nanoparticles are capable of being exogenously loaded with a wide range of therapeutic cargo. Endogenous origin confers biocompatibility, while nanoscale size enables EVs to overcome the various biological barriers with ease, making them a promising drug delivery platform that can be harnessed for the treatment of several disease conditions. Moreover, the components present on the EV surface can be modified for enhanced loading to achieve a more precise targeted cargo delivery. This comprehensive review summarizes the current literature on exogenously cargo-loaded EVs, including their exogenous loading methods, targeting mechanisms, intracellular delivery, clinical translation, biodistribution, and <em>in vivo</em> visualization. The review also discusses preclinical studies utilizing cargo-loaded EVs for treating various disease conditions, while highlighting the commonly encountered clinical and regulatory hurdles in the successful translation of exogenous cargo-loaded EV-based therapeutics.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107473"},"PeriodicalIF":4.9,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}