Green synthesized biocompatible polymers of amphiphilic nature can be used for enhancing the solubility and permeability of BCS Class-IV drugs. Thus, different grades of novel polylactic acid (PLA) grafted Hibiscus rosasinensis leaf mucilage (HLM) amphiphilic graft copolymer (HLM-g-PLA) were synthesized for improving the solubility and permeability characteristics of drugs like Curcumin. Optimized grade G1 was characterized using FTIR, 13C NMR, TGA, XRD, OCA and DLS. The critical micelle concentration (CMC) of G1 was found to be low indicating surfactant properties which were evidenced by its ability to stabilize colloidal dispersion. In vitro drug release study revealed 62.86 % of curcumin (CUR) release for more than 20 h, indicating sustained release properties, following Korsmeyer-Peppas model, indicating nonfickian diffusion with n > 0.5. The solubility and permeability of CUR were enhanced to 6.2013 ± 1.8142 μg/ml from 0.5254 ± 0.0342 μg/ml and 15.754 ± 0.7877 % respectively, in the presence of G1. The optimized grade G1 exhibited antimicrobial activity against Staphylococcus aureus and Escherichia coli with anti-inflammatory and hemocompatible properties. G1 also exhibited wound healing with no traces of scars and full hair growth within 11 days, indicating its biocompatible nature, thereby indicating the application of such natural polysaccharide modified amphiphilic graft copolymers as an effective pharmaceutical excipient.
{"title":"Solubility enhancement of curcumin using PLA-grafted Hibiscus rosa-sinensis mucilage as a biocompatible amphiphilic copolymer","authors":"Biswasarathi Basak, Laxmi Kumari, Trishna Bal, Shreya Sharma, Akash Mondal, Joydeep Bhattacharyya","doi":"10.1016/j.jddst.2026.108033","DOIUrl":"10.1016/j.jddst.2026.108033","url":null,"abstract":"<div><div>Green synthesized biocompatible polymers of amphiphilic nature can be used for enhancing the solubility and permeability of BCS Class-IV drugs. Thus, different grades of novel polylactic acid (PLA) grafted <em>Hibiscus rosasinensis</em> leaf mucilage (HLM) amphiphilic graft copolymer (HLM-g-PLA) were synthesized for improving the solubility and permeability characteristics of drugs like Curcumin. Optimized grade G1 was characterized using FTIR, <sup>13</sup>C NMR, TGA, XRD, OCA and DLS. The critical micelle concentration (CMC) of G1 was found to be low indicating surfactant properties which were evidenced by its ability to stabilize colloidal dispersion<em>. In vitro</em> drug release study revealed 62.86 % of curcumin (CUR) release for more than 20 h, indicating sustained release properties, following Korsmeyer-Peppas model, indicating nonfickian diffusion with n > 0.5. The solubility and permeability of CUR were enhanced to 6.2013 ± 1.8142 μg/ml from 0.5254 ± 0.0342 μg/ml and 15.754 ± 0.7877 % respectively, in the presence of G1. The optimized grade G1 exhibited antimicrobial activity against <em>Staphylococcus aureus and Escherichia coli</em> with anti-inflammatory and hemocompatible properties<em>.</em> G1 also exhibited wound healing with no traces of scars and full hair growth within 11 days, indicating its biocompatible nature, thereby indicating the application of such natural polysaccharide modified amphiphilic graft copolymers as an effective pharmaceutical excipient.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108033"},"PeriodicalIF":4.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035467","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}
Pub Date : 2026-01-21DOI: 10.1016/j.jddst.2026.108046
Jiazhen Zhu , Haonan Zhang , Jinmin Lin , Yuqi Wang , Zheng Shi , Fanzhu Li , Wendong Yao
Strychni semen contains bioactive total alkaloids effective against osteoarthritis (OA). However, their utility is limited by rapid clearance and potential toxicity to the central nervous system (CNS) and kidneys. To overcome these limitations, we developed a novel transdermal delivery system utilizing transfersomes loaded with majorizing Strychni semen total alkaloids (M-SSA-TFSs). Compared with conventional liposomes, M-SSA-TFSs demonstrated excellent stability, high drug encapsulation efficiency, and significantly enhanced skin permeation. Pharmacodynamic and pharmacokinetic evaluations using double-sited microdialysis confirmed that M-SSA-TFSs significantly inhibited pro-inflammatory cytokines, protected cartilage structure, and maintained sustained therapeutic drug levels in both the joint cavity and systemic circulation. Furthermore, the delivery system demonstrated favorable biocompatibility with healthy chondrocytes while exhibiting therapeutic efficacy against OA. Consequently, this study highlights M-SSA-TFSs as a superior transdermal approach that improves the dermal absorption and therapeutic index of Strychni semen, providing a valuable strategy for decelerating OA progression.
{"title":"Development and evaluation of Strychni semen total alkaloid-loaded transfersomes for targeted articular delivery in osteoarthritis","authors":"Jiazhen Zhu , Haonan Zhang , Jinmin Lin , Yuqi Wang , Zheng Shi , Fanzhu Li , Wendong Yao","doi":"10.1016/j.jddst.2026.108046","DOIUrl":"10.1016/j.jddst.2026.108046","url":null,"abstract":"<div><div>Strychni semen contains bioactive total alkaloids effective against osteoarthritis (OA). However, their utility is limited by rapid clearance and potential toxicity to the central nervous system (CNS) and kidneys. To overcome these limitations, we developed a novel transdermal delivery system utilizing transfersomes loaded with majorizing Strychni semen total alkaloids (M-SSA-TFSs). Compared with conventional liposomes, M-SSA-TFSs demonstrated excellent stability, high drug encapsulation efficiency, and significantly enhanced skin permeation. Pharmacodynamic and pharmacokinetic evaluations using double-sited microdialysis confirmed that M-SSA-TFSs significantly inhibited pro-inflammatory cytokines, protected cartilage structure, and maintained sustained therapeutic drug levels in both the joint cavity and systemic circulation. Furthermore, the delivery system demonstrated favorable biocompatibility with healthy chondrocytes while exhibiting therapeutic efficacy against OA. Consequently, this study highlights M-SSA-TFSs as a superior transdermal approach that improves the dermal absorption and therapeutic index of Strychni semen, providing a valuable strategy for decelerating OA progression.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108046"},"PeriodicalIF":4.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074418","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}
Pub Date : 2026-01-21DOI: 10.1016/j.jddst.2026.108027
Maria Gioia Fabiano , Linda Maurizi , Jacopo Forte , Eleonora D'Intino , Maria Grazia Ammendolia , Davide Corinti , Astri D. Tagueha , Michela Relucenti , Orlando Donfrancesco , Federica Rinaldi , Maria Elisa Crestoni , Stefania Garzoli , Carlotta Marianecci , Maria Carafa , Catia Longhi
Nanocarrier-based drug delivery systems (DDS) offer promising strategies to enhance therapeutic efficacy, stability, and targeted delivery of bioactive compounds while reducing side effects. In this study, a multidisciplinary approach was employed to develop and characterize bioactive liposomes incorporating resveratrol (RV), a polyphenol with known therapeutic potential but limited bioavailability, and Thymus vulgaris essential oil (TEO), recognized for its antimicrobial and antioxidant properties. To obtain stable nanocarriers, liposomes were formulated using soy lecithin and prepared by thin layer evaporation technique followed by sonication process. To assess the preservation of TEO's chemical profile during formulation, Headspace Solid Phase Microextraction coupled with Gas Chromatography–Mass Spectrometry (HS-SPME/GC-MS) was performed. Quantitative analysis of thymol and carvacrol, the two main active components, was performed by HPLC-UV experiments. Physicochemical characterization of DDS was carried out employing Dynamic Light Scattering (DLS), UV–Vis spectrophotometer and Transmission electron microscopy. Antimicrobial activity was assessed by broth microdilution method, while biofilm inhibition ability was evaluated using crystal violet staining. The obtained nanocarriers exhibited appropriate physicochemical characteristics, including optimal particle size and stability. They can efficiently load both oil and RV. These features enhanced the antibacterial activity of LT-RV compared to free RV, and improved its inhibitory effect, at sub-MIC concentrations, against the sessile form of Listeria monocytogenes strains.
This study highlights the importance of integrating chemical, physical, and biological evaluations to develop effective nanocarrier-based formulations with the aim to identify a suitable strategy to combat infections associated with resistant, biofilm-producing pathogens, and offer a versatile and effective delivery platform.
{"title":"A green strategy for resveratrol nanodelivery: A multidisciplinary approach for the physicochemical characterization of Thymus-based liposomes with anti-biofilm activity against Listeria monocytogenes","authors":"Maria Gioia Fabiano , Linda Maurizi , Jacopo Forte , Eleonora D'Intino , Maria Grazia Ammendolia , Davide Corinti , Astri D. Tagueha , Michela Relucenti , Orlando Donfrancesco , Federica Rinaldi , Maria Elisa Crestoni , Stefania Garzoli , Carlotta Marianecci , Maria Carafa , Catia Longhi","doi":"10.1016/j.jddst.2026.108027","DOIUrl":"10.1016/j.jddst.2026.108027","url":null,"abstract":"<div><div>Nanocarrier-based drug delivery systems (DDS) offer promising strategies to enhance therapeutic efficacy, stability, and targeted delivery of bioactive compounds while reducing side effects. In this study, a multidisciplinary approach was employed to develop and characterize bioactive liposomes incorporating resveratrol (RV), a polyphenol with known therapeutic potential but limited bioavailability, and <em>Thymus vulgaris</em> essential oil (TEO), recognized for its antimicrobial and antioxidant properties. To obtain stable nanocarriers, liposomes were formulated using soy lecithin and prepared by thin layer evaporation technique followed by sonication process. To assess the preservation of TEO's chemical profile during formulation, Headspace Solid Phase Microextraction coupled with Gas Chromatography–Mass Spectrometry (HS-SPME/GC-MS) was performed. Quantitative analysis of thymol and carvacrol, the two main active components, was performed by HPLC-UV experiments. Physicochemical characterization of DDS was carried out employing Dynamic Light Scattering (DLS), UV–Vis spectrophotometer and Transmission electron microscopy. Antimicrobial activity was assessed by broth microdilution method, while biofilm inhibition ability was evaluated using crystal violet staining. The obtained nanocarriers exhibited appropriate physicochemical characteristics, including optimal particle size and stability. They can efficiently load both oil and RV. These features enhanced the antibacterial activity of LT-RV compared to free RV, and improved its inhibitory effect, at sub-MIC concentrations, against the sessile form of <em>Listeria monocytogenes</em> strains.</div><div>This study highlights the importance of integrating chemical, physical, and biological evaluations to develop effective nanocarrier-based formulations with the aim to identify a suitable strategy to combat infections associated with resistant, biofilm-producing pathogens, and offer a versatile and effective delivery platform.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108027"},"PeriodicalIF":4.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035414","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}
Targeted drug delivery systems are crucial for cancer treatment, as they boost therapeutic effectiveness while minimizing systemic toxicity. In this study, we developed pH-degradable hollow mesoporous silica nanoparticles (HMON) functionalized with hyaluronic acid (HA) for CD44-targeted drug delivery. Aryl imine organosilane was utilized to confer pH-responsiveness to the HMON, enabling controlled drug release in the mildly acidic tumor microenvironment. In vitro studies have shown that DOX@HMON-HA significantly enhances DOX uptake in CD44-overexpressing tumor cells, such as HeLa and HCT-116, leading to substantial cytotoxic effects. In contrast, CD44-low expressing cells like MCF-7 exhibit minimal DOX uptake and reduced cytotoxicity. In vivo studies further validated the therapeutic efficacy of DOX@HMON-HA, showing effective tumor growth suppression without observable systemic toxicity. These findings underscore the potential of pH-degradable hyaluronan (HA)-modified silica nanoparticles as an effective strategy for targeted cancer therapy.
{"title":"CD44-targeted and pH-degradable hollow mesoporous silica nanocarriers for cancer therapy","authors":"Yi-Ching Tsai , Natesan Thirumalaivasan , Shu-Pao Wu","doi":"10.1016/j.jddst.2026.108045","DOIUrl":"10.1016/j.jddst.2026.108045","url":null,"abstract":"<div><div>Targeted drug delivery systems are crucial for cancer treatment, as they boost therapeutic effectiveness while minimizing systemic toxicity. In this study, we developed pH-degradable hollow mesoporous silica nanoparticles (HMON) functionalized with hyaluronic acid (HA) for CD44-targeted drug delivery. Aryl imine organosilane was utilized to confer pH-responsiveness to the HMON, enabling controlled drug release in the mildly acidic tumor microenvironment. In vitro studies have shown that <strong>DOX@HMON-HA</strong> significantly enhances DOX uptake in CD44-overexpressing tumor cells, such as HeLa and HCT-116, leading to substantial cytotoxic effects. In contrast, CD44-low expressing cells like MCF-7 exhibit minimal DOX uptake and reduced cytotoxicity. In vivo studies further validated the therapeutic efficacy of <strong>DOX@HMON-HA</strong>, showing effective tumor growth suppression without observable systemic toxicity. These findings underscore the potential of pH-degradable hyaluronan (HA)-modified silica nanoparticles as an effective strategy for targeted cancer therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108045"},"PeriodicalIF":4.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035466","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}
Pub Date : 2026-01-21DOI: 10.1016/j.jddst.2026.108019
Antoinette G. Naeem , Diana M.F. Hanna , Haidy E. Michel , Dina O. Helal , Ebtehal El-Demerdash
Doxorubicin (DOX) therapy results in cognitive impairment, known as “chemobrain”. Calcitriol (CAL) confers neuroprotection in many neuropathologies. Our objective was to develop a nose-to-brain nanocarrier-based delivery system of CAL for enhanced brain targeting and efficacy. CAL was loaded in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the nanoprecipitation technique. Effects of formulation parameters on NPs physicochemical properties were evaluated. The neuroprotective effect of oral CAL solution (100 ng/kg/day) or intranasal CAL solution or CAL-NPs (30 ng/kg/day) was assessed in DOX-induced chemobrain rat model by neurobehavioral, histopathological, and biochemical assessments. CAL-NPs composed of 10 mg PLGA, 0.1 % Tween® 80 and 30 μg CAL were optimum for nose-to-brain delivery with particle size, polydispersity index, zeta potential, and entrapment efficiency of 164 ± 5.47 nm, 0.18 ± 0.02, −18.3 ± 0.6 mV, and 51.39 ± 1.53 %, respectively. Transmission electron microscope imaging confirmed the formation of spherical particles, and in vitro drug release showed a biphasic pattern with sustained drug release up to one week. Intranasal CAL treatment enhanced cognition, restored hippocampal histoarchitecture, and suppressed acetylcholinesterase activity. CAL hindered hippocampal neuroinflammation by enhancing sirtuin (SIRT) 1 expression and mitigating the cGAS/STING/p-TBK-1/NF-κB p65 axis and its effector cytokines. In addition, it suppressed p-IRE-1α/XBP-1s endoplasmic reticulum stress axis and its downstream pro-apoptotic CCAAT/enhancer binding protein homologous (CHOP) and caspase-3. Collectively, intranasal administration of CAL, particularly via PLGA NPs, enhanced CAL neuroprotective effect at one-third the oral dose, suggesting the potential use of CAL-NPs as a promising nose-to-brain delivery system for mitigation of DOX-induced chemobrain.
{"title":"Intranasal calcitriol-loaded PLGA nanoparticles attenuate doxorubicin-induced cognitive impairment in rats via cGAS/STING and endoplasmic reticulum stress crosstalk","authors":"Antoinette G. Naeem , Diana M.F. Hanna , Haidy E. Michel , Dina O. Helal , Ebtehal El-Demerdash","doi":"10.1016/j.jddst.2026.108019","DOIUrl":"10.1016/j.jddst.2026.108019","url":null,"abstract":"<div><div>Doxorubicin (DOX) therapy results in cognitive impairment, known as “chemobrain”. Calcitriol (CAL) confers neuroprotection in many neuropathologies. Our objective was to develop a nose-to-brain nanocarrier-based delivery system of CAL for enhanced brain targeting and efficacy. CAL was loaded in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the nanoprecipitation technique. Effects of formulation parameters on NPs physicochemical properties were evaluated. The neuroprotective effect of oral CAL solution (100 ng/kg/day) or intranasal CAL solution or CAL-NPs (30 ng/kg/day) was assessed in DOX-induced chemobrain rat model by neurobehavioral, histopathological, and biochemical assessments. CAL-NPs composed of 10 mg PLGA, 0.1 % Tween® 80 and 30 μg CAL were optimum for nose-to-brain delivery with particle size, polydispersity index, zeta potential, and entrapment efficiency of 164 ± 5.47 nm, 0.18 ± 0.02, −18.3 ± 0.6 mV, and 51.39 ± 1.53 %, respectively. Transmission electron microscope imaging confirmed the formation of spherical particles, and <em>in vitro</em> drug release showed a biphasic pattern with sustained drug release up to one week. Intranasal CAL treatment enhanced cognition, restored hippocampal histoarchitecture, and suppressed acetylcholinesterase activity. CAL hindered hippocampal neuroinflammation by enhancing sirtuin (SIRT) 1 expression and mitigating the cGAS/STING/p-TBK-1/NF-κB p65 axis and its effector cytokines. In addition, it suppressed p-IRE-1α/XBP-1s endoplasmic reticulum stress axis and its downstream pro-apoptotic CCAAT/enhancer binding protein homologous (CHOP) and caspase-3. Collectively, intranasal administration of CAL, particularly <em>via</em> PLGA NPs, enhanced CAL neuroprotective effect at one-third the oral dose, suggesting the potential use of CAL-NPs as a promising nose-to-brain delivery system for mitigation of DOX-induced chemobrain.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108019"},"PeriodicalIF":4.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074416","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}
Low water solubility and extensive hepatic first-pass metabolism limit oral bioavailability of Nebivolol hydrochloride (NEB), a new-generation β-blocker agent effective in hypertension treatment. To overcome such issues, a combined strategy was applied, based on the development of orally disintegrating films (ODFs) loaded with NEB as SBEβCD complex. This approach exploits both the SBEβCD solubilizing power and the fast drug dissolution in the oral cavity provided by ODF. Preformulation studies allowed to select the best combinations of film-forming polymers (PVA in mixture with Na alginate or HPMC) and plasticizer (PEG 400) to obtain ODFs with the desired properties. Loading of selected ODF formulations with NEB-SBEβCD complex significantly increased its dissolution rate: >50 % drug dissolved in simulated saliva after 5′ and 100 % in simulated gastric medium within 30’. In contrast, the plain drug achieved only 30 % and 70 % dissolution, respectively.
This should enhance the drug fraction absorbed in the pre-gastric tract, limiting hepatic first-pass metabolism. Moreover, SBEβCD caused a significant reduction of the film disintegration time, due to the higher water-affinity of the drug-CD complex than free drug. Finally, the drug entrapment within the CD cavity should prevent palatability problems related to drug bitter taste, avoiding addition of flavoring agents.
{"title":"Development and characterization of orally disintegrating films of Nebivolol as complex with Sulfobutylether-β-cyclodextrin","authors":"Marzia Cirri , Silvia Fiani , Francesca Maestrelli , Natascia Mennini , Maria Cristina Salvatici , Paola Mura","doi":"10.1016/j.jddst.2026.108043","DOIUrl":"10.1016/j.jddst.2026.108043","url":null,"abstract":"<div><div>Low water solubility and extensive hepatic first-pass metabolism limit oral bioavailability of Nebivolol hydrochloride (NEB), a new-generation β-blocker agent effective in hypertension treatment. To overcome such issues, a combined strategy was applied, based on the development of orally disintegrating films (ODFs) loaded with NEB as SBEβCD complex. This approach exploits both the SBEβCD solubilizing power and the fast drug dissolution in the oral cavity provided by ODF. Preformulation studies allowed to select the best combinations of film-forming polymers (PVA in mixture with Na alginate or HPMC) and plasticizer (PEG 400) to obtain ODFs with the desired properties. Loading of selected ODF formulations with NEB-SBEβCD complex significantly increased its dissolution rate: >50 % drug dissolved in simulated saliva after 5′ and 100 % in simulated gastric medium within 30’. In contrast, the plain drug achieved only 30 % and 70 % dissolution, respectively.</div><div>This should enhance the drug fraction absorbed in the pre-gastric tract, limiting hepatic first-pass metabolism. Moreover, SBEβCD caused a significant reduction of the film disintegration time, due to the higher water-affinity of the drug-CD complex than free drug. Finally, the drug entrapment within the CD cavity should prevent palatability problems related to drug bitter taste, avoiding addition of flavoring agents.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108043"},"PeriodicalIF":4.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074404","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}
Pub Date : 2026-01-21DOI: 10.1016/j.jddst.2026.108003
Hande Maden , Hilal Calik , Rabia Yilmaz Ozturk , Selcen Ari Yuka , Betül Zehra Temur , Özge Can , Gizem Dinler Doğanay , Rabia Cakir
Colorectal cancer is the second most common cause of cancer-related deaths worldwide. Most of these deaths are due to failure of chemotherapy caused by drug resistance and resulting tumor recurrence. Therefore, overcoming drug resistance is crucial for the successful treatment of colorectal cancer. In this study, the P5S3 peptide selected by bioinformatics analysis for inhibiting drug resistance and the 5-FU drug were loaded into chitosan nanoparticles and investigated in vitro on drug-resistant colorectal cancer cells. Firstly, P5S3 was identified as a peptide inhibitor by MDR1 binding site-specific molecular docking analyses and in silico prediction of biological and physicochemical properties. The peptide was synthesized using the solid phase synthesis method and characterized by RP-HPLC and LC-MS/MS. Chitosan nanoparticles loaded with 5-FU and P5S3 (5-FU/P5S3@CSNPs) were synthesized using an ionic gelation method and characterized using a ZetaSizer, FT-IR, FE-SEM, and UV–Vis. The 5-FU/P5S3@CSNPs were approximately 110 nm in size and spherical in shape, and had a good encapsulation efficiency and loading capacity. Furthermore, drug resistance was conferred to sensitive HCT-116 cells (HCT-116/FU) that were continuously exposed to 5-FU, and the development of drug resistance was confirmed by qPCR. The effect of 5-FU/P5S3@CSNPs on cell viability in HCT-116/FU cells and their inhibitory activities on MDR1 drug efflux pumps were analyzed by XTT and accumulation assay, respectively. Our results demonstrate that the 5-FU/P5S3@CSNPs had high anticancer potential against HCT-116/FU cells and high inhibition ability of MDR1. In conclusion, our findings suggest that 5-FU/P5S3@CSNPs offer a promising approach for the treatment of resistant colorectal cancer.
{"title":"In silico–designed peptide targeting MDR1 (P-gp) restores chemosensitivity in colorectal cancer via chitosan nanoparticle delivery","authors":"Hande Maden , Hilal Calik , Rabia Yilmaz Ozturk , Selcen Ari Yuka , Betül Zehra Temur , Özge Can , Gizem Dinler Doğanay , Rabia Cakir","doi":"10.1016/j.jddst.2026.108003","DOIUrl":"10.1016/j.jddst.2026.108003","url":null,"abstract":"<div><div>Colorectal cancer is the second most common cause of cancer-related deaths worldwide. Most of these deaths are due to failure of chemotherapy caused by drug resistance and resulting tumor recurrence. Therefore, overcoming drug resistance is crucial for the successful treatment of colorectal cancer. In this study, the P5S3 peptide selected by bioinformatics analysis for inhibiting drug resistance and the 5-FU drug were loaded into chitosan nanoparticles and investigated <em>in vitro</em> on drug-resistant colorectal cancer cells. Firstly, P5S3 was identified as a peptide inhibitor by MDR1 binding site-specific molecular docking analyses and <em>in silico</em> prediction of biological and physicochemical properties. The peptide was synthesized using the solid phase synthesis method and characterized by RP-HPLC and LC-MS/MS. Chitosan nanoparticles loaded with 5-FU and P5S3 (5-FU/P5S3@CSNPs) were synthesized using an ionic gelation method and characterized using a ZetaSizer, FT-IR, FE-SEM, and UV–Vis. The 5-FU/P5S3@CSNPs were approximately 110 nm in size and spherical in shape, and had a good encapsulation efficiency and loading capacity. Furthermore, drug resistance was conferred to sensitive HCT-116 cells (HCT-116/FU) that were continuously exposed to 5-FU, and the development of drug resistance was confirmed by qPCR. The effect of 5-FU/P5S3@CSNPs on cell viability in HCT-116/FU cells and their inhibitory activities on MDR1 drug efflux pumps were analyzed by XTT and accumulation assay, respectively. Our results demonstrate that the 5-FU/P5S3@CSNPs had high anticancer potential against HCT-116/FU cells and high inhibition ability of MDR1. In conclusion, our findings suggest that 5-FU/P5S3@CSNPs offer a promising approach for the treatment of resistant colorectal cancer.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108003"},"PeriodicalIF":4.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035413","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}
Pub Date : 2026-01-20DOI: 10.1016/j.jddst.2026.108029
Jing Zhang , Jing Wen , Tie Li , Junshuang Xu , Jinbiao Ma , Min Hong , Wei Li
Hyperuricemia (HU), a common metabolic disorder, is characterized by elevated serum uric acid (sUA) levels. Uricase, an enzyme that degrades uric acid(UA) into allantoin, is absent in humans due to a nonsense mutation. Messenger RNA (mRNA)-based protein replacement therapy, known for its efficiency and transient expression, has garnered significant research attention. This study focuses on developing a mRNA therapy for HU using human ancestral uricase ANC19, delivered via lipid nanoparticles (LNPs). We prepared ANC19-LNPs, characterized their physicochemical properties, and evaluated their expression and function in Huh7 cells. Results indicate successful preparation and characterization of ANC19-mRNA, which localizes to peroxisomes and demonstrates UA degradation capability in vitro. Biodistribution was validated in Balb/c mice. Concurrently, a HU mouse model was successfully established using siRNA-mediated knockdown of Uricase-mRNA. In HU mouse models, ANC19-LNPs achieved a 75.63 % UA degradation rate. To validate these promising findings in a more clinically relevant species, the therapy was evaluated in cynomolgus monkeys, where it also showed a therapeutic effect, the area under the curve (AUC) of the concentration-time curve for ANC19-LNPs was 32.647 h∗μg/mL compared to 67.074 h∗μg/mL for the negative control. Biochemical blood tests in cynomolgus monkeys confirmed the safety of ANC19-LNPs. In conclusion, we have successfully developed an effective mRNA-based protein replacement therapy for UA degradation, showing promising efficacy and safety in both in vitro and in vivo studies.
{"title":"Preclinical development and evaluation of Uricase mRNA-loaded lipid nanoparticles for the treatment of hyperuricemia","authors":"Jing Zhang , Jing Wen , Tie Li , Junshuang Xu , Jinbiao Ma , Min Hong , Wei Li","doi":"10.1016/j.jddst.2026.108029","DOIUrl":"10.1016/j.jddst.2026.108029","url":null,"abstract":"<div><div>Hyperuricemia (HU), a common metabolic disorder, is characterized by elevated serum uric acid (sUA) levels. Uricase, an enzyme that degrades uric acid(UA) into allantoin, is absent in humans due to a nonsense mutation. Messenger RNA (mRNA)-based protein replacement therapy, known for its efficiency and transient expression, has garnered significant research attention. This study focuses on developing a mRNA therapy for HU using human ancestral uricase ANC19, delivered via lipid nanoparticles (LNPs). We prepared ANC19-LNPs, characterized their physicochemical properties, and evaluated their expression and function in Huh7 cells. Results indicate successful preparation and characterization of ANC19-mRNA, which localizes to peroxisomes and demonstrates UA degradation capability in vitro. Biodistribution was validated in Balb/c mice. Concurrently, a HU mouse model was successfully established using siRNA-mediated knockdown of Uricase-mRNA. In HU mouse models, ANC19-LNPs achieved a 75.63 % UA degradation rate. To validate these promising findings in a more clinically relevant species, the therapy was evaluated in cynomolgus monkeys, where it also showed a therapeutic effect, the area under the curve (AUC) of the concentration-time curve for ANC19-LNPs was 32.647 h∗μg/mL compared to 67.074 h∗μg/mL for the negative control. Biochemical blood tests in cynomolgus monkeys confirmed the safety of ANC19-LNPs. In conclusion, we have successfully developed an effective mRNA-based protein replacement therapy for UA degradation, showing promising efficacy and safety in both in vitro and in vivo studies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108029"},"PeriodicalIF":4.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035419","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}
Pub Date : 2026-01-20DOI: 10.1016/j.jddst.2026.108038
Jong-Soo Choi , Jae-Won Park , Dong Kyu Choi , Jin Hong Lee , Gi-Baek Kwon , Ji-Hoon Shin , Kyung-Oh Doh
Cationic cholesterol liposomes offer the advantage of binding affinity to nucleic acids and stability in the serum. Additionally, the cationic cholesterol serves as a helper lipid enhancing the bio distribution of lipid nanoparticles. β-sitosterol, with its branched C-24 ethyl group in the tail of the sterol backbone, influences membrane structure. Because of this structural difference, β-sitosterol containing LNPs may exhibit efficient cellular uptake and gene expression. Therefore, we synthesized the cationic sitosterol derivative through amidation of the 3-hydroxy group of β-sitosterol, followed by conversion to the nitrile, reduction of the nitrile and deprotection of the BOC group. The final compound was incorporated as a lipid component for the liposomal formulation. Replacing cationic cholesterol with the cationic sitosterol derivative in liposomes significantly enhanced gene delivery of plasmid DNA, mRNA and siRNA. The liposome comprising an equal ratio of cationic cholesterol and sitosterol (C1S1) exhibited 3–5 fold increases of GFP pDNA expression in CHO and HeLa cells compared to liposomes containing only cationic cholesterol or sitosterol. It also showed 1.5-fold increases of GFP mRNA expression in CHO and HeLa cells.
This improvement in gene delivery was attributed to 2-fold increase in cellular uptake and more efficient endosomal escape. However, in an in vivo model, the liposome formulated exclusively with cationic sitosterol demonstrated the highest mRNA expression. This discrepancy suggests that in vivo data cannot always be predicted through in vitro data likely due to physiological barriers such as reticuloendothelial system and serum aggregation in vivo.
{"title":"Optimization of β-sitosterol–based cationic liposomes for gene delivery in vitro and in vivo","authors":"Jong-Soo Choi , Jae-Won Park , Dong Kyu Choi , Jin Hong Lee , Gi-Baek Kwon , Ji-Hoon Shin , Kyung-Oh Doh","doi":"10.1016/j.jddst.2026.108038","DOIUrl":"10.1016/j.jddst.2026.108038","url":null,"abstract":"<div><div>Cationic cholesterol liposomes offer the advantage of binding affinity to nucleic acids and stability in the serum. Additionally, the cationic cholesterol serves as a helper lipid enhancing the bio distribution of lipid nanoparticles. β-sitosterol, with its branched C-24 ethyl group in the tail of the sterol backbone, influences membrane structure. Because of this structural difference, β-sitosterol containing LNPs may exhibit efficient cellular uptake and gene expression. Therefore, we synthesized the cationic sitosterol derivative through amidation of the 3-hydroxy group of β-sitosterol, followed by conversion to the nitrile, reduction of the nitrile and deprotection of the BOC group. The final compound was incorporated as a lipid component for the liposomal formulation. Replacing cationic cholesterol with the cationic sitosterol derivative in liposomes significantly enhanced gene delivery of plasmid DNA, mRNA and siRNA. The liposome comprising an equal ratio of cationic cholesterol and sitosterol (C1S1) exhibited 3–5 fold increases of GFP pDNA expression in CHO and HeLa cells compared to liposomes containing only cationic cholesterol or sitosterol. It also showed 1.5-fold increases of GFP mRNA expression in CHO and HeLa cells.</div><div>This improvement in gene delivery was attributed to 2-fold increase in cellular uptake and more efficient endosomal escape. However, in an <em>in vivo</em> model, the liposome formulated exclusively with cationic sitosterol demonstrated the highest mRNA expression. This discrepancy suggests that <em>in vivo</em> data cannot always be predicted through <em>in vitro</em> data likely due to physiological barriers such as reticuloendothelial system and serum aggregation <em>in vivo</em>.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108038"},"PeriodicalIF":4.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035417","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}
Pub Date : 2026-01-19DOI: 10.1016/j.jddst.2026.108034
Mingming Li , Suhong Fu , Jiaxin Chen , Xinxing Sun , Yang Chen , Lei Yang
High-quality wound healing is a primary clinical goal, yet it remains difficult to achieve reliably with current treatments. For this purpose, this study developed an ion-paired asiatic acid (AA) hydrogel specially for wound healing and systematically evaluated its pharmacodynamic efficacy both in vitro and in vivo. The formulation strategy involved screening organic amines as counter-ions using an ex vivo stratum corneum-removed skin model. Triethanolamine was identified as the optimal counterion, maximizing AA penetration into local tissue while minimizing systemic permeation via the formation of an ion-pair as confirmed by Nuclear Magnetic Resonance. The resulting hydrogel exhibited ideal properties for wound application, as characterized by its water vapor transmission rate, swelling ratio, degradability ratio, and water retention. In vitro, the hydrogel accelerated wound closure by stimulating cellular proliferation and migration, promoting vascular differentiation, and exhibiting selective antibacterial efficacy against S. aureus. In a rat full-thickness skin defect model, the hydrogel effectively facilitated scarless healing, which was mechanistically linked to collagen remodeling (indicated by a higher proportion of type III relative to type I collagen), suppression of TNF-α-mediated inflammation, and downregulation of TGF-β-driven fibrosis. Collectively, this work establishes a strategically designed ion-pair hydrogel system that coordinates key healing processes, offering a promising strategy for achieving reliable, high-quality wound regeneration.
{"title":"Ion-paired asiatic acid hydrogel facilitates high-quality wound healing through diverse synergistic effects","authors":"Mingming Li , Suhong Fu , Jiaxin Chen , Xinxing Sun , Yang Chen , Lei Yang","doi":"10.1016/j.jddst.2026.108034","DOIUrl":"10.1016/j.jddst.2026.108034","url":null,"abstract":"<div><div>High-quality wound healing is a primary clinical goal, yet it remains difficult to achieve reliably with current treatments. For this purpose, this study developed an ion-paired asiatic acid (AA) hydrogel specially for wound healing and systematically evaluated its pharmacodynamic efficacy both in vitro and in vivo. The formulation strategy involved screening organic amines as counter-ions using an ex vivo stratum corneum-removed skin model. Triethanolamine was identified as the optimal counterion, maximizing AA penetration into local tissue while minimizing systemic permeation via the formation of an ion-pair as confirmed by Nuclear Magnetic Resonance. The resulting hydrogel exhibited ideal properties for wound application, as characterized by its water vapor transmission rate, swelling ratio, degradability ratio, and water retention. <em>In vitro</em>, the hydrogel accelerated wound closure by stimulating cellular proliferation and migration, promoting vascular differentiation, and exhibiting selective antibacterial efficacy against <em>S. aureus</em>. In a rat full-thickness skin defect model, the hydrogel effectively facilitated scarless healing, which was mechanistically linked to collagen remodeling (indicated by a higher proportion of type III relative to type I collagen), suppression of TNF-α-mediated inflammation, and downregulation of TGF-β-driven fibrosis. Collectively, this work establishes a strategically designed ion-pair hydrogel system that coordinates key healing processes, offering a promising strategy for achieving reliable, high-quality wound regeneration.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108034"},"PeriodicalIF":4.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035464","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}
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