International Journal of Pharmaceutics最新文献

{"title":"Can bacteriophage be stabilised by lipid encapsulation when nebulised for inhalation delivery against Pseudomonas aeruginosa?","authors":"Yue Cao ,&nbsp;Yuncheng Wang ,&nbsp;Mengyu Li ,&nbsp;Dipesh Khanal ,&nbsp;Hak-Kim Chan","doi":"10.1016/j.ijpharm.2025.125670","DOIUrl":"10.1016/j.ijpharm.2025.125670","url":null,"abstract":"<div><div>Inhaled bacteriophage (phage) therapy is emerging as a promising approach to combat multidrug-resistant (MDR) respiratory pathogens such as <em>Pseudomonas aeruginosa</em>. Aerosol delivery by nebulization poses challenges for maintaining phage stability, often resulting in titer losses due to mechanical stresses. This study evaluated the use of liposomal encapsulation to protect phages during nebulization. Two <em>P. aeruginosa</em> phages, PEV2 (short-tail) and PEV40 (long-tail), were selected for this work. Liposomes were prepared using DSPC, cholesterol, Tween 80, and cationic lipid DOTAP. Encapsulation efficiencies were 78 % for PEV2 and 90 % for PEV40, with mean particle sizes of 300 nm and 650 nm, respectively. Nebulization by jet and vibrating mesh devices showed that the liposome-encapsulated phages were able to preserve viability, with titer losses below 0.4 log₁₀ (PEV40) and 0.07 log₁₀ (PEV2). In contrast, non-encapsulated phages experienced titer reductions of up to 1.23 log₁₀, especially by jet nebulization. Vibrating mesh nebulization generated slightly larger droplets (∼5.6 µm) but with better phage recovery (&gt; 90 %) and respirable fractions (&gt; 70 %) for both types of phages encapsulated in liposomes. These results demonstrate that the approach of lipid encapsulation effectively protects phages from mechanical damage during nebulization, maintaining bioactivity for aerosol delivery to enhance the success of inhaled phage therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125670"},"PeriodicalIF":5.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective ocular delivery of antioxidant polyphenols using elastin-like polymer nanosystems developed by sustainable process","authors":"Luna Krstić ,&nbsp;Reinaldo Vallejo ,&nbsp;Soraya Rodriguez-Rojo ,&nbsp;María J. González-García ,&nbsp;F. Javier Arias ,&nbsp;Alessandra Girotti ,&nbsp;Yolanda Diebold","doi":"10.1016/j.ijpharm.2025.125691","DOIUrl":"10.1016/j.ijpharm.2025.125691","url":null,"abstract":"<div><div>The present study is centred on the development of a therapeutic strategy for Dry Eye Disease (DED), and all experimental models, formulation designs, and outcome measures have been specifically tailored to address this pathology. Elastin-like polymers (ELPs) are emerging as a groundbreaking nanobiomaterial for advanced drug delivery systems, thanks to their biomimetic, adaptable, and stimuli-responsive properties. Embracing sustainability, we employed supercritical CO₂ (scCO₂) as an eco-friendly alternative to organic solvents to develop an innovative ELP-based particulate system. This system, designed for topical ophthalmic applications, incorporates two antioxidant and anti-inflammatory polyphenolic compounds, quercetin (QUE) and resveratrol (RSV), through a one-step supercritical antisolvent (SAS) process. Post-SAS process, we achieved solid microparticles loaded with QUE, RSV, or a combination of both. Remarkably, these microparticles transform into nanoparticles (NPs) with an average size of 56.7 ± 1.0 to 61.5 ± 2.6 nm when placed in solution at physiological temperature. This transformation leverages the stimulus-responsive nature of ELP, ensuring sustained polyphenol release. Our ELP-based formulations demonstrate exceptional biocompatibility with Human Corneal Epithelial cells (HCEs) and exhibit outstanding intracellular scavenging activity against reactive oxygen species (ROS). To track cellular uptake, we developed particles with a two fluorescent tags. This system successfully delivered the fluorescent payload to cells and efficiently targeted the corneal epithelium in <em>ex vivo</em> porcine eye globes, showcasing time-dependent delivery.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125691"},"PeriodicalIF":5.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision medicine for acute kidney injury: Baicalein-nanodrug delivery system combat oxidative stress and repair mitochondrial dysfunction","authors":"Xue Zhou ,&nbsp;Ning Wang ,&nbsp;Bin Zhao ,&nbsp;Ziquan Liu ,&nbsp;Pei Yu","doi":"10.1016/j.ijpharm.2025.125694","DOIUrl":"10.1016/j.ijpharm.2025.125694","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is characterized by high morbidity and mortality globally and serves as an independent risk factor for chronic kidney disease. Oxidative stress is the main pathogenic mechanism leading to acute kidney injury (AKI) and subsequent renal failure, which is characterized by excessive reactive oxygen species (ROS) and mitochondrial dysfunction. Treatment options for AKI remain supportive care, it is urgent to develop more viable therapeutic strategies. In this study, we engineered a nanodrug delivery system aiming to achieve precise treatment of AKI. The nanocarriers (Apt-NS) exhibited excellent serum stability and biocompatibility and were capable of specifically recognizing AKI renal tubular cells. Apt-NS were loaded with baicalein (BAI) to form a nanodrug delivery system (Apt-NS-BAI). In comparison to the BAI, Apt-NS-BAI demonstrated more pronounced effects in improving cell viability, scavenging ROS and anti-apoptosis. Simultaneously, <em>in vivo</em> animal experiments also confirmed that Apt-NS-BAI could recognize the injury site and exert biological functions of anti-apoptosis and alleviating renal damage. Overall, this study successfully constructed a nanodrug delivery system with the ability to target AKI renal tubular cells, enabling accurate and efficient delivery of baicalein to injury site and exerting protective functions against oxidative stress. This research offers novel insights into the precision treatment of AKI and contributes to the acceleration of the application of nanotechnology in kidney diseases.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125694"},"PeriodicalIF":5.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational design of DXd derivatives for liposomal drug delivery: Towards safer and more effective cancer treatments","authors":"Jinbo Li ,&nbsp;Jiang Yu ,&nbsp;Baoyue Zhang ,&nbsp;Jia Song ,&nbsp;Ruiping Huang ,&nbsp;Ning Li ,&nbsp;Yingxi Zhang ,&nbsp;Shuang Zhou ,&nbsp;Xin Li ,&nbsp;Zhonggui He ,&nbsp;Hongzhuo Liu ,&nbsp;Yongjun Wang","doi":"10.1016/j.ijpharm.2025.125688","DOIUrl":"10.1016/j.ijpharm.2025.125688","url":null,"abstract":"<div><div>DXd (Exatecan derivative), a novel TOPO-I inhibitor, exhibits high membrane permeability and an efficient bystander effect, serving as a critical cytotoxic drug component in antibody-drug conjugates (ADCs). However, its poor stability, high toxicity and non-ionizable structure limit its clinical applications. Basic/acid/metal coordination modifying strategy offers a potential solution to remotely load non-ionizable drugs into liposomes. However, achieving an optimal balance between therapeutic efficacy and safety remains a major challenge. In this study, DXd was used as a model compound to design and synthesize a series of weakly basic derivatives (DXdd), incorporating various basic moieties linked via alkyl chains of different lengths. The alkyl chain length significantly influenced both the chemical stability and antitumor activity of DXdd. Among them, DXdd with four alkyl chains (DXdd-4PA) demonstrated potent antitumor efficacy with minimal acute and cumulative toxicity. Subsequent optimization of the liposome size loaded with DXdd-4PA revealed that 80 nm was optimal for cancer therapy. Overall, this work provides a valuable framework for the rational design of non-ionizable drugs suitable for remote loading into liposomes, and enhances the translational potential of DXd-based therapeutics.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125688"},"PeriodicalIF":5.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural characterization and immune activity evaluation of polysaccharide purified from Viola phillipica","authors":"Jinhang Guo ,&nbsp;Tiantian Wei ,&nbsp;Jiafa Chen ,&nbsp;Ancan Hong ,&nbsp;Qiuyue He ,&nbsp;Yi Lin ,&nbsp;Zhe Ren ,&nbsp;Tao Qin","doi":"10.1016/j.ijpharm.2025.125689","DOIUrl":"10.1016/j.ijpharm.2025.125689","url":null,"abstract":"<div><div>This study investigated the structure of <em>Viola phillipica</em> polysaccharide (VPP) and its effect as an immune adjuvant for the Newcastle disease vaccine (ND Vaccine). The results showed that VPP comprised of the galacturonic acid, galactose, rhamnose, arabinose with the molar ratio of 36.20: 23.41: 19.72: 11.54 and a molecular weight (Mw) of 1080 kDa. Additionally, the composition of VPP was assessed via FT-IR, methylation, AFM and SEM analyses, indicating that the backbone of the VPP was consisted of T-Ara (f), T-Gal (p), 4-Gal (p)-UA, and T-Rha (p) linkages. Furthermore, VPP was used as an immune adjuvant in combination with ND vaccine in chickens. Remarkable enhancements were observed in the thymus, spleen, and bursa indices of the chickens, the serum levels of ND antibodies and the expression of IL-4 and IFN-γ cytokines, thereby fostering the proliferation of T and B lymphocytes within the spleen. Notably, histopathological analysis indicated that the VPP groups showed increased lymphoid follicles and splenic nodules, as well as greater splenic red pulp density and bursa of Fabricius area. In summary, these findings suggest that VPP could serve as an adjuvant to enhance the immunogenicity of NDV.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125689"},"PeriodicalIF":5.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acoustically responsive monodisperse nanodroplets stabilized with biocompatible fluorinated surfactants","authors":"Romain Melich ,&nbsp;Stéphane Desgranges ,&nbsp;Philippe Bussat ,&nbsp;Christiane Contino-Pépin ,&nbsp;Samir Cherkaoui","doi":"10.1016/j.ijpharm.2025.125680","DOIUrl":"10.1016/j.ijpharm.2025.125680","url":null,"abstract":"<div><div>Phase-changed contrast agents are receiving increased popularity in both ultrasound diagnostic as contrast agents, and therapeutic application as ultrasound-cavitation nuclei. A main limitation of perfluorocarbon nanodroplets (PFC-ND) is their relatively limited physicochemical stability over time, which may affect their use for diagnostic and therapy purposes. A possible strategy to overcome this issue has been identified in the selection of biocompatible surfactants constituting the nanodroplets shell. This study investigates the formulation and characterization of stable perfluorocarbon nanodroplets using a microfluidic approach. Firstly, we present the structure and synthesis of two families of biocompatible fluorinated surfactants (BFS) called “F-TAC” and “DendriTAC” stabilizing the nanodroplets shell, while perfluoropentane is used as liquid core. The influence of various formulation and process parameters, including surfactant type, surfactant/PFC ratio, dilution factor, flow rate ratio and storage conditions, on the physicochemical properties and acoustic vaporization behavior of the nanodroplets was investigated. The nanoprecipitation process combined to a microfluidic approach has proven to be a powerful approach for the preparation of PFC-NDs with precise size control and uniform particle distribution. As expected, the choice of surfactant and process parameters significantly influenced the NDs size and stability. Both classes of BFS resulted in nanodroplets exhibiting notable stability, which was further enhanced by the addition of trehalose, especially under freezing conditions. All formulations, regardless of their specific shell composition, vaporized at comparable vaporizable thresholds. Our findings highlight the importance of formulation parameters, and process settings in controlling the properties of these nanostructures. In conclusion, this study provides valuable insights into the formulation and optimization of perfluorocarbon nanodroplets for potential biomedical applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125680"},"PeriodicalIF":5.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in superparamagnetic nanogels: A dual-role platform for diagnosis and targeted drug delivery","authors":"Anil Pareek ,&nbsp;Sanjesh Kumar ,&nbsp;Devesh U. Kapoor ,&nbsp;Bhupendra G Prajapati","doi":"10.1016/j.ijpharm.2025.125683","DOIUrl":"10.1016/j.ijpharm.2025.125683","url":null,"abstract":"<div><div>Superparamagnetic nanogels represent a groundbreaking advancement in nanotechnology, combining the unique properties of superparamagnetic materials with the versatility of nanogels to create multifunctional platforms for biomedical applications. These innovative constructs play a dual role in diagnosis and targeted drug delivery, addressing critical challenges in modern healthcare. This review paper explores the synthesis, characterization, and applications of superparamagnetic nanogels, providing a comprehensive overview of their potential impact in biomedicine. The synthesis section outlines various materials, fabrication techniques, and surface functionalization methods used to enhance their functionality and biocompatibility. Characterization techniques are discussed, focusing on their structural, magnetic, and biological properties. In diagnostic applications, superparamagnetic nanogels excel as contrast agents for magnetic resonance imaging, biosensors, and tools for real-time disease monitoring. Their superior sensitivity and specificity offer unprecedented opportunities for early disease detection and personalized treatment. In drug delivery, these nanogels demonstrate remarkable efficiency in encapsulating therapeutic agents and enabling controlled release. Magnetic guidance enhances targeting precision, minimizing off-target effects and improving therapeutic outcomes, particularly in cancer therapy. The dual-role capability of these nanogels underscores their potential as transformative tools in precision medicine. This review emphasizes recent advancements, highlighting the challenges and future perspectives in optimizing superparamagnetic nanogels for clinical translation. By bridging the gap between innovative design and practical application, this work aims to inspire further research and development in this dynamic field.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125683"},"PeriodicalIF":5.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to sterilize biodegradable polymers? An in-depth characterization of effects of low energy electron beam irradiation (LEEI) and gamma irradiation on the molecular weight of poly(lactide-co-glycolide) films","authors":"Jan Krieghoff ,&nbsp;Gaby Gotzmann ,&nbsp;Tobias Teichmann ,&nbsp;Michaela Schulz-Siegmund","doi":"10.1016/j.ijpharm.2025.125684","DOIUrl":"10.1016/j.ijpharm.2025.125684","url":null,"abstract":"<div><div>Ionizing radiation is routinely used for sterilization of medical and biomedical products. The most commonly used radiation type for this purpose, gamma rays, features several drawbacks related to the high energy of the radiation, such as being restricted to dedicated external facilities. Low energy electron irradiation (LEEI) is an alternative type of irradiation, suitable for sterilization with significantly lower material penetration, allowing in-process implementation with smaller shielding, but also requiring more involved sample preparation. In this study, we investigated the effect of comparable doses of LEEI and gamma irradiation on the molecular weight distribution of thin films made from PLGA, a biodegradable polyester that is a biomaterial of interest for the design of medical devices and medicinal products such as microparticles for controlled drug release. For the study, the PLGA films were placed into sealed packaging with an inert helium atmosphere, and the effect of this packaging on LEEI absorption was calculated in order to correlate the measured dose under the package to the dose received by the sealed films. For both radiation types, irradiation resulted in a decrease of the PLGA molecular weight that became more pronounced at higher doses. Comparing low energy electrons and gamma rays, no significant differences were found in the characteristic parameters of the molecular weight distribution at the same dose range. Together, these results indicate that single product in-process sterilization by LEEI may be a suitable approach for medical devices and products from PLGA.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"678 ","pages":"Article 125684"},"PeriodicalIF":5.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of amiodarone between lipid nanocapsules and residual micelles: Tangential flow filtration as a purification method and its impact on cytotoxicity","authors":"Jaspe Chen ,&nbsp;Sophie Tamareille ,&nbsp;Etienne Chèvremont ,&nbsp;Jean-Christophe Gimel ,&nbsp;Brice Calvignac ,&nbsp;David Dallerac ,&nbsp;Nolwenn Lautram ,&nbsp;Tanguy Le Lay ,&nbsp;Clara Rapenne ,&nbsp;Isabelle Verdu ,&nbsp;Patrick Saulnier ,&nbsp;Émilie Martinez ,&nbsp;Guillaume Lefebvre","doi":"10.1016/j.ijpharm.2025.125651","DOIUrl":"10.1016/j.ijpharm.2025.125651","url":null,"abstract":"<div><div>Amiodarone (AMD) is an anti-arrhythmic drug prescribed for the treatment of atrial fibrillation. Despite its efficiency, AMD causes several extracardiac side effects due to its highly lipophilic nature, limiting its clinical use. Lipid nanocapsules (LNCs) are a promising approach for encapsulating AMD and altering its whole-body biodistribution. It has been established that during the phase inversion composition process to prepare LNCs loaded with AMD (LNC-AMD), some residual micelles will also be formed. These residual micelles could contain AMD and impact the formulation’s cytotoxicity. In this study, we present a scalable tangential flow filtration (TFF) process for the separation of micelles from LNCs. Subsequently, dynamic light scattering and asymmetric flow-field flow fractionation in combination with UV and RI detections are subtly associated with a mass balance to assess the efficiency of TFF in removing free polyethylene glycol and surfactant micelles. An encapsulation efficiency of 91 % in the LNCs was calculated with a drug loading of 7.2 mg per gram of dry matter constituting the LNCs. Finally, the cytotoxicity of the LNC vector and LNC-AMD candidate nanomedicines, both purified and non-purified, was evaluated on H9C2, A549, and HepG2 cell lines. It has been demonstrated that the elimination of free polyethylene glycol and residual surfactant micelles results in a substantial enhancement in cell viability. The cytotoxic results raise questions about the cell-specific uptake and distribution of purified LNCs.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125651"},"PeriodicalIF":5.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-purposing of linagliptin for enhanced wound healing and skin rejuvenation via chitosan- modified PLGA nanoplatforms","authors":"Fatma Sa’eed El-Tokhy ,&nbsp;Dina O. Helal ,&nbsp;Sherif S. Abdel Mageed ,&nbsp;Abdulla M.A. Mahmoud ,&nbsp;Riham I. El-Gogary ,&nbsp;Elsayed A. El-Ghany ,&nbsp;Mona M.A. Abdel-Mottaleb","doi":"10.1016/j.ijpharm.2025.125664","DOIUrl":"10.1016/j.ijpharm.2025.125664","url":null,"abstract":"<div><div>Dipeptidyl peptidase IV (DPP IV) is a multifunctional glycoprotein implicated in the exacerbation of various inflammatory skin conditions, including wounds. Therefore, topical delivery of Linagliptin (LNG)-a DPP IV inhibitor- augmented with Lavender Oil (LO) could offer an excellent repurposed tool for the treatment of inflammatory skin diseases. LNG/ LO loaded chitosan (Cs) −modified Poly (Lactide co-Glycolic Acid) (PLGA) nanoparticles (LNG/LO-Cs/PLGA NPs) were prepared by solvent emulsification-evaporation technique. D-optimal design explored the impact of independent factors namely; ratio of LO: PLGA, percentage of surfactant, and type of PLGA on; particle size, zeta potential, and entrapment efficiency of NPs. The optimized formulation displayed positively charged, homogeneous small-sized particles (159.34 nm), with high entrapment efficiency (89.30 %w/w). The <em>in vitro</em> release profile of the optimized NPs showed an initial burst release (16.6 %) after one hour, followed by an extended-release pattern for three days. Transmission electron microscopy showed spherical matrix particles with a slightly denser coat. An <em>ex-vivo</em> skin permeation study revealed notable LNG deposition in rat skin (51 % w/w after 24 h). Confocal laser scanning microscopy confirmed the time-dependent enhanced penetration of nanocarriers into the skin. <em>In-vivo</em> study done on induced-wound model revealed accelerated wound healing in NPs-treated group with 86.49 % wound contraction. Biochemical analysis of the impacted skin showed lower oxidative stress, with a 2.5-fold rise in reduced glutathione, a 3.2-fold boost in total antioxidant capacity, a 3.3-fold drop in malondialdehyde, and a 4.5-fold decrease in TNF-α levels versus the positive control. Therefore,This nanosystem could stand as a novel gateway and repurposed tool for accelerated wound healing and tissue regeneration.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125664"},"PeriodicalIF":5.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}