Journal of Drug Delivery Science and Technology最新文献

{"title":"Cyclodextrin-based supramolecular dissolving microneedles for enhanced transdermal delivery of azelaic acid in acne vulgaris treatment","authors":"Yuxu Chen,&nbsp;Yuanyu Xu,&nbsp;Jingqing Zhang,&nbsp;Xinjun Xu","doi":"10.1016/j.jddst.2025.107108","DOIUrl":"10.1016/j.jddst.2025.107108","url":null,"abstract":"<div><div>Acne vulgaris is a common skin condition affecting individuals of various age groups, significantly impacting their quality of life. Although azelaic acid (AZA) is widely used in acne treatment due to its anti-inflammatory, antibacterial, and tyrosinase inhibitory properties, its low aqueous solubility limits its transdermal absorption and reduces therapeutic efficacy. Dissolving microneedles (DMNs), fabricated from water-soluble materials, have shown great potential as a strategy for improving transdermal drug delivery. However, DMNs face challenges in encapsulating poorly soluble drugs like AZA. In this study, we developed cyclodextrin-based supramolecular DMNs loaded with AZA, in which the microneedles are composed entirely of inclusion complexes to enhance the transdermal delivery efficiency of AZA for treating acne. AZA was encapsulated into hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) using a solvent evaporation technique, resulting in respective 34.9-fold and 25.4-fold increases in AZA solubility. The inclusion complexes demonstrated superior antibacterial activity in inhibition zone assays and enhanced tyrosinase inhibitory activity compared to free AZA in aqueous solution, suggesting enhanced dispersion and biological activity. The DMNs exhibited excellent mechanical strength and maintained a high drug-loading capacity of AZA, facilitating efficient penetration through the stratum corneum. <em>In vitro</em> permeation test showed 24-h percutaneous permeability rates at 68.69 ± 3.79 % and 73.59 ± 4.23 % for AZA/HP-β-CD DMNs and AZA/SBE-β-CD DMNs, respectively. Additionally, the DMNs demonstrated no cytotoxicity toward L929 cells and displayed hemocompatibility. Overall, the developed supramolecular DMNs system presents a promising approach for enhancing the transdermal delivery of AZA, with the potential to enhance therapeutic outcomes in acne treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107108"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230509","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":"Effect of inlet swirl on dry powder distribution through the oropharyngeal route of human respiratory tract","authors":"Anurag Tiwari ,&nbsp;Akshoy Ranjan Paul ,&nbsp;Anuj Jain","doi":"10.1016/j.jddst.2025.107097","DOIUrl":"10.1016/j.jddst.2025.107097","url":null,"abstract":"<div><div>This study utilized computational fluid dynamics (CFD) to investigate the impact of swirling airflow on dry powder drug particle transport and deposition in a realistic human respiratory tract model extending from the oral cavity to the sixth bronchial bifurcation. The model incorporated steady-state inspiratory flow conditions and discrete phase modeling to simulate the behavior of 1 μm–25 μm particles at various flow rates (5–45 L/min), swirl numbers (SN = 0, 0.25, 0.4, 0.85), and swirl directions (clockwise [CW] and anticlockwise [ACW]).</div><div>The results demonstrated that moderate swirling flow improves drug targeting in the distal lung. Specifically, a CW swirl at Sn = 0.4 with a low flow rate of 10 L/min achieved the most efficient deposition, delivering approximately 75 % of 5 μm particles to the distal region, while minimizing unwanted deposition in the oropharyngeal region. At a standard condition of 30 L/min and 1 μm particles, a CW swirl at SN = 0.4 yielded the highest in the distal region deposition (51.37 %) compared to only 23.97 % in the no-swirl case.</div><div>Flow visualization confirmed that the swirl promotes favorable jet redirection and enhanced particle residence time, while maintaining wall shear stress within physiologically safe limits. Excessive swirl (SN = 0.85) increased deposition in the oropharyngeal region, due to inertial impaction. These findings highlight the potential of controlled swirl, especially CW swirl at low flow rates, as a practical strategy to improve DPI design for targeted pulmonary drug delivery.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107097"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189993","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":"Site-specific delivery of pectin-stabilized gold nanoparticles for liver: An in vivo evaluation with Doxorubicin","authors":"Mayank Kumar Singh ,&nbsp;Sophia Mckenzie Schulte ,&nbsp;Rohith Kumar ,&nbsp;Shilpa Kumar ,&nbsp;Swati Singh ,&nbsp;Abhay Singh Chauhan","doi":"10.1016/j.jddst.2025.107118","DOIUrl":"10.1016/j.jddst.2025.107118","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the most common (80–85%) form of liver cancer. Doxorubicin (DOX) is a well-known highly potent anti-cancer drug but still lags due to its formulation, stability issues and other physicochemical properties leading to suboptimal performance. The use of gold nanoparticles as a drug delivery system has become one of the most promising strategies, especially in areas like cancer therapy where targeted and controlled drug release is crucial. We have developed an advanced gold nanoparticle (GNP) system using natural polysaccharide (Pectin). The dual functionality of pectin works as a stabilizer for GNP and also ensures liver-specific drug delivery via Asialoglycoprotein (ASGP) receptors expressed on the surface of liver cells. The present study aims to synthesize, characterize and explore the potential of pectin-stabilized gold nanoparticles (P-GNP) using DOX for liver targeting (in vivo). The P-GNP-DOX hydrodynamic diameter was 99.80±2.21 nm, which was further corroborated by AFM. UV–visible spectroscopy indicated molecular interactions between DOX and P-GNP through characteristic red-shifts in the surface plasmon resonance band. Electrostatic interaction was also evidenced by FT-IR and 1H NMR. The P-GNP-DOX demonstrated prolonged in vitro drug release and better stability profile in physiological conditions compared to its commercially available Doxotero® Injection. The targeting efficiency of the P-GNP-DOX was evaluated in preclinical (living animal) studies using a non-invasive in vivo imaging system. The P-GNP-DOX showed better liver targeting potential compared to the DOX alone. It is the first preclinical in vivo study of pectin-stabilized gold nanoparticles and results indicate that it could be a promising platform for the liver targeting.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107118"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204681","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":"Retraction notice to “Trilazad mesylate-loaded electrospun cellulose acetate nanofibrous wound dressings promote diabetic wound healing by modulation of immune response and protection against oxidative damage” [J. Drug Deliv. Sci. Technol. 69 (2021) 102863]","authors":"Lei Lei ,&nbsp;Weihong Huang ,&nbsp;Ke Liu ,&nbsp;Xiaobo Liu ,&nbsp;Mingbin Dai ,&nbsp;Zhichuan Liu ,&nbsp;Yongjian Zhiao","doi":"10.1016/j.jddst.2025.107035","DOIUrl":"10.1016/j.jddst.2025.107035","url":null,"abstract":"","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107035"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242409","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":"Multifunctional NiO-curcumin nanocomposite-loaded chitosan-alginate scaffolds for enhanced bone tissue regeneration and antibacterial activity","authors":"Logesh Kumar Sellappan ,&nbsp;Shivam Mishra ,&nbsp;Sruthi Sundaresan ,&nbsp;Thenmalarchelvi Rathinavelan ,&nbsp;Saptarshi Majumdar","doi":"10.1016/j.jddst.2025.107114","DOIUrl":"10.1016/j.jddst.2025.107114","url":null,"abstract":"<div><div>Regenerating infected bone tissue requires advanced biomaterials that integrate mechanical strength, antibacterial properties, and biomineralization potential. Here, we developed bioactive chitosan-alginate (CA) scaffolds reinforced with nickel oxide-curcumin (NiO-Cur) nanocomposites (CANC) using sol-gel synthesis, chemical crosslinking, and freeze-drying. The incorporation of NiO-Cur nanocomposites enhanced the scaffolds structural and functional properties, as confirmed by ATR-FTIR, XRD, FE-SEM, and EDAX analyses. The scaffolds exhibited better compressive strength (406.1 ± 3.79 KPa), high porosity (85.72 ± 1.01 % to 91.08 ± 1.19 %) with interconnected honeycomb-like pores (114–132 μm), facilitating nutrient diffusion and cellular infiltration. Enhanced compressive strength and rheological properties (G′ &gt; G′′) demonstrated their ability to dissipate shear stress and withstand dynamic loads, critical for bone tissue engineering. Cur release profiles for CANC1, CANC2, and CANC3 scaffolds after 72 h were 72.05 %, 78.32 %, and 83.95 %, respectively. Additionally, CANC scaffolds also displayed superior hydrophilicity, promoting swelling and controlled degradation under physiological conditions. <em>In vitro</em> biomineralization studies revealed dense apatite formation within 14 days in simulated body fluid, favouring osteoconductive potential. Additionally, CANC scaffolds exhibited significant antibacterial activity with zone of inhibition value of (10.78 ± 0.23 mm) against <em>Staphylococcus aureus</em> and (8.05 ± 0.2 mm) <em>Escherichia coli</em>, suggesting efficacy in preventing post-surgical infections. The synergistic interaction between NiO-Cur nanocomposites and the CA matrix improved physicochemical, mechanical, and rheological stability, alongside enhanced antibacterial efficacy and apatite-forming potential. Preclinical studies could further validate the potential of CANC scaffolds to accelerate bone healing, reduce recovery time in infected bone injuries, and advance tissue regeneration applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107114"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204179","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":"Non-invasive fast-acting lidocaine HCl lozenges for ventricular Arrhythmia: Formulation, optimization, and in vivo pharmacodynamic study","authors":"Hetal P. Patel ,&nbsp;Aashka H. Bhatt ,&nbsp;Pruthil A. Tejani ,&nbsp;Priyanshi R. Patel ,&nbsp;Rutvi J. Vaidya ,&nbsp;Bhavin A. Vyas ,&nbsp;Furqan A. Maulvi","doi":"10.1016/j.jddst.2025.107113","DOIUrl":"10.1016/j.jddst.2025.107113","url":null,"abstract":"<div><div>Ventricular arrhythmia is a severe, life-threatening condition that demands immediate medical intervention. Intravenous (IV) lidocaine hydrochloride (HCl) is widely used for emergency management; however, its invasive administration and requirement for medical supervision limit its practicality. While oral administration is a more patient-friendly alternative, lidocaine HCl exhibits only 35 % oral bioavailability due to extensive hepatic first-pass metabolism, leading to inconsistent systemic drug levels. This study aimed to develop lidocaine HCl hard candy lozenges as a non-invasive, fast-acting alternative that leverages oral mucosal absorption to enhance bioavailability and accelerate onset of action. A Central Composite Design (CCD) was employed to optimize the formulation by evaluating the effects of sucrose (X₁) and HPMC E5 (X₂) on drug release (Y₁) and mouth dissolving time (Y₂). Lozenges were prepared using the heating and congealing technique and were assessed for physical properties, in vitro drug release, and <em>in vivo</em> pharmacodynamics. The optimized formulation demonstrated uniform shape, smooth texture, and high mechanical strength, ensuring ease of handling and patient acceptability. It achieved 97.31 % lidocaine HCl release within 5 min and a mouth dissolution time of 11.27 min, confirming rapid systemic availability. Pharmacodynamic evaluation using a calcium chloride-induced ventricular arrhythmia rat model revealed a significant reduction in arrhythmic episodes, with normalization of cardiac electrical activity within 10 min of administration. The rapid therapeutic response was attributed to the formulation's fast dissolution and efficient mucosal absorption, which bypass first-pass metabolism and mimics the rapid action of IV lidocaine HCl. Thus, lidocaine HCl hard candy lozenges provide a novel, non-invasive alternative for ventricular arrhythmia management, overcoming the limitations of injectable formulations while ensuring patient compliance. Future studies should focus on clinical validation, long-term stability, and expanding applications in emergency cardiac care.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107113"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169332","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":"Exploring roflumilast transferosomes in pluronic-hyaluronic acid hydrogel through comprehensive in-vitro and in-vivo evaluation","authors":"Ahmed Abdelaziz ,&nbsp;Mariam Zewail ,&nbsp;Haidy Abbas ,&nbsp;Maged W. Helmy ,&nbsp;Doaa A. Habib","doi":"10.1016/j.jddst.2025.107081","DOIUrl":"10.1016/j.jddst.2025.107081","url":null,"abstract":"<div><div>Roflumilast (RF) is a phosphodiesterase-4 inhibitor that has been recently approved to treat psoriasis. This study aims to enhance the topical anti-psoriasis pharmacological effect of RF through the preparation of RF-loaded transferosomes (TRFs) and loading them in a poloxamer-hyaluronic acid hydrogel. TRF were prepared through the ethanol injection technique in which different ratios of lipid: surfactant was examined to determine the optimum formula. F4 and F12 with two different drug concentrations (0.1 % and 0.2 %) were found to be the most optimized formulations according to the <em>in-vitro</em> characterizations. These formulations had the highest percentage of drug release after 24 h (102.74 % and 106.95 %, respectively), high EE % (81.9 % and 91.2 %, respectively), and small vesicle size (101.4 nm and 218.5 nm, respectively). F4 and F12 were then incorporated into poloxamer-hyaluronic acid hydrogel followed by further in-vivo examination. <em>In vivo</em> pharmacological study assessed the possible positive impact of RF-TRF Hydrogel in treating psoriasis by utilizing an Imiquimod (IMQ)-induced psoriasis-like mouse model. Psoriasis Area Severity Index <em>(</em>PASI) was employed to assess the inflammation severity on the backs of mice concerning erythema, thickness, and scaling scoring. Histopathological examination to evaluate epidermal thickness and immunohistochemical analysis to determine proliferating cell nuclear antigen (PCNA) expression in mice's lesional skin also were employed. Our findings indicated that RF-TRF hydrogel effectively decreased the PASI scores. Histopathological examination showed a significant decrease in epidermal thickness. Additionally, RF-TRF hydrogel successfully reduced the expression of PCNA in the skin lesions caused by IMQ in mice. In conclusion, our work showed that RF-TRF hydrogel showed significant enhancement of the anti-psoriasis effect.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107081"},"PeriodicalIF":4.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168839","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":"Acalabrutinib loaded nanostructured lipid carriers to improve the oral delivery of the drug: Optimization, physicochemical characterization, in vivo pharmacokinetics and lymphatic uptake studies","authors":"Swagata Sinha,&nbsp;Punna Rao Ravi,&nbsp;Kotgire Prathmesh,&nbsp;Barun Ghosh","doi":"10.1016/j.jddst.2025.107100","DOIUrl":"10.1016/j.jddst.2025.107100","url":null,"abstract":"<div><div>Nanostructured lipid carriers (NLCs) offer a promising solution for improving the delivery of lipophilic drugs by enhancing solubility, bioavailability, and targeting, though optimizing their physicochemical properties, such as particle size and drug loading, remains challenging. Traditional one-factor-at-a-time methods fail to account for complex interactions among variables, so this study employs a design of experiments approach to optimize NLCs for oral delivery of acalabrutinib, using a 2⁵⁻¹ fractional factorial design for screening followed by a circumscribed central composite design for optimization. The optimized NLCs exhibited spherical morphology with a mean particle size of 249.3 ± 9.1 nm with PDI of 0.349 ± 0.036, 10.69 ± 0.51 % loading and 77.51 ± 3.72 % entrapment efficiency. The <em>in vitro</em> release of acalabrutinib from the NLCs followed square root kinetics with 100 % drug release at the end of 48 h in pH 7.2. The formulation exhibited stable particle size and entrapment efficiency with minimum deviations when stored at 5 °C for 6 months. Oral pharmacokinetic studies showed that NLCs nanosuspension enhanced C_max and AUC_0-tlast by 2.17- and 4.35-folds (p &lt; 0.001) compared to conventional suspension. Additionally, NLCs sustained plasma drug concentrations longer, with an MRT_0-tlast of 6.97 h vs. 3.61 ± 0.19 h for the conventional suspension. Inhibiting the lymphatic flow reduced the AUC_0-tlast by 44.14 %, highlighting the significant role played by lymphatic transport in the oral absorption NLCs. This study underscores the potential of the developed NLCs as an effective platform for oral delivery of acalabrutinib.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107100"},"PeriodicalIF":4.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189994","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":"Thermo-engineered zinc-alginate and pectin stabilized hydroxyapatite microspheres: A synergistic approach for bone repair and drug delivery","authors":"Muthulakshmi Vaikundam ,&nbsp;Kumar Ponnuchamy ,&nbsp;Amutha Santhanam","doi":"10.1016/j.jddst.2025.107096","DOIUrl":"10.1016/j.jddst.2025.107096","url":null,"abstract":"<div><div>This study reports the development of thermally engineered Zn-alginate-pectin stabilized hydroxyapatite (pHAP) microsphere for enhanced bone repair and targeted drug delivery. The microspheres were synthesized via a green route using <em>carrot pomace</em>-derived pectin mediated HAP with alginate, offering a biocompatible and biodegradable platform that mimics bone mineral. Incorporation of Zn²⁺ through Zn(NO₃)₂ cross-linking improved osteo conductivity, while calcination at 1000 °C facilitated phase transformation and zinc substitution into the HAP lattice, enhancing structural integrity and bioactivity. <em>In vitro</em> studies using MG-63 cells confirmed improved cell proliferation, ALP activity, and biomineralization, supporting their role in bone repair. In parallel, the system served as an efficient drug delivery platform by separately loading doxorubicin (DOX) and methotrexate (MTX). Drug release studies for both the drugs revealed a sustained and pH-responsive profile, with faster release under acidic conditions mimicking the tumour microenvironment. Cytotoxicity assays on MCF-7 and A549 cancer cells demonstrated significant, dose-dependent antiproliferative effects, with DOX-loaded microspheres showing higher potency. Apoptotic analysis (AO/EB and Hoechst staining) and migration/invasion studies (Scratch and Trans well assays) confirmed enhanced cancer cell inhibition. This dual-functional microsphere combines structural support for bone regeneration with controlled, localized chemotherapeutic delivery. The outcome results of this study highlighted that the integration of thermal engineering with biopolymers and zinc doping presents a unique and effective strategy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107096"},"PeriodicalIF":4.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178773","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":"Mechano-chemically activated co-amorphous of oleanolic acid and sodium cholate: enhancement of solubility, dissolution and bioactivity against visceral pain in a rat model of colitis","authors":"Francesco Baldi ,&nbsp;Clara Ciampi ,&nbsp;Lorenzo Di Cesare Mannelli ,&nbsp;Muhammad Wasim ,&nbsp;Maria Cristina Salvatici ,&nbsp;Carla Ghelardini ,&nbsp;Anna Rita Bilia ,&nbsp;Maria Camilla Bergonzi","doi":"10.1016/j.jddst.2025.107110","DOIUrl":"10.1016/j.jddst.2025.107110","url":null,"abstract":"<div><div>This study aimed to enhance the solubility and bioavailability of oleanolic acid (OA), a highly insoluble compound, using a mechanochemical approach to form co-ground (COG) with sodium cholate (NaC). Through high-energy grinding in a ball mill, the binary COG was prepared, and then characterized and evaluated. The initial screening of ten hydrophilic carriers identified NaC as the most effective, forming a COG with OA in a 1:1 wt ratio after 30 min of grinding. Detailed characterizations, including DSC, FT-IR, XRPD, and SEM, identified the mechanisms behind the substantial solubility enhancement of OA, achieving up to 623 μg/mL, and confirmed the formation of the co-ground. The formation of a co-amorphous structure, and the establishment of intermolecular interactions between OA and NaC were identified as key factors contributing to this improvement. Dissolution tests revealed that COG achieved an 80 % dissolution rate of OA within 2 h, compared to just 30 % for pure OA, demonstrating the effectiveness of COG in maintaining high solubility and preventing recrystallization. <em>In vivo</em> tests on a rat model of DNBS-induced colitis showed promising results. The acute administration of COG significantly reduced visceral pain compared to unformulated OA, suggesting enhanced bioavailability and therapeutic efficacy. While pure OA 15 mg/kg is inactive, COG 30 mg/kg, composed of OA 15 mg/kg and NaC 15 mg/kg, displays a statistically significant pharmacological effect, with a percentage reduction in AUC equal to 40 %. This research highlights the potential of mechanochemical activation in developing effective OA formulations, offering a green chemistry solution that is efficient, solvent-free, and environmentally friendly. The study provides a solid foundation for further exploration of OA-based treatments for chronic inflammatory conditions and pain management.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107110"},"PeriodicalIF":4.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169348","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}