International Journal of Pharmaceutics: X最新文献

{"title":"Gemini surfactant-stabilized cubosomes for enhanced topical delivery of 5-fluorouracil in cutaneous squamous cell carcinoma","authors":"Ruchira Raychaudhuri ,&nbsp;Ajinkya Nitin Nikam ,&nbsp;Naitik Jain ,&nbsp;Abhisheik Eedara ,&nbsp;Neha Kandpal ,&nbsp;Rajdeep Ray ,&nbsp;Krishnadas Nandakumar ,&nbsp;Sai Balaji Andugulapati ,&nbsp;Srinivas Mutalik","doi":"10.1016/j.ijpx.2026.100504","DOIUrl":"10.1016/j.ijpx.2026.100504","url":null,"abstract":"<div><div>Cutaneous squamous cell carcinoma (cSCC) is a prevalent non-melanoma skin cancer. Topical chemotherapy offers a non-invasive alternative to surgical treatments, yet the therapeutic efficacy of conventional agents like 5-fluorouracil is hindered by poor skin permeability and systemic side effects. In this study, we developed a gemini-surfactant-stabilized cubosomal gel (OF12-GEL) for enhanced topical delivery of 5-fluorouracil. The optimized cubosomes (OF12) exhibited a particle size of 134.4 nm, PDI 0.23, zeta potential +76.1 mV, and 51.3% entrapment efficiency. OF12-GEL achieved 41% release at 24 h and increased skin deposition to 323.7 μg/cm², nearly 3-fold higher than free 5-FU (114.1 μg/cm²). In A431 cells, OF12 showed a lower IC₅₀ (0.77 μg/mL) than free 5-FU (1.15 μg/mL) and enhanced cellular uptake. <em>In vivo</em>, OF12-GEL significantly suppressed tumor growth in both DMBA-induced SCC rats and A431 xenograft mice, reducing tumor volume by and improving survival to 60%, and markedly downregulating BCL-2, Ki67, TNF-α, and ABCB1. OF12-GEL was non-irritant (PII = 0.33). These findings demonstrate a potent, safe, and targeted nanocarrier-based topical therapy for cSCC.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100504"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188933","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":"Recent advances in lipid nanoparticles for cancer vaccine delivery: Challenges and future perspectives","authors":"Nurhasni Hasan ,&nbsp;Maryam Aftab ,&nbsp;Sania Ikram ,&nbsp;Apon Zaenal Mustofa ,&nbsp;Sriwidodo Sriwidodo ,&nbsp;Huda Shalahudin Darusman ,&nbsp;Muhammad Nur Amir ,&nbsp;Theofilus A. Tockary ,&nbsp;Satoshi Uchida","doi":"10.1016/j.ijpx.2026.100484","DOIUrl":"10.1016/j.ijpx.2026.100484","url":null,"abstract":"<div><div>Cancer remains a major global health burden, with 19.3 million new cases and 10.3 million deaths reported in 2020. Conventional modalities such as surgery, radiotherapy, and chemotherapy often fail to prevent metastasis or recurrence. Cancer vaccination, which mobilizes durable, tumor-specific immunity, has gained traction, and LNPs have become pivotal to this approach. Originally optimized for siRNA, LNPs’ core–shell architecture protects nucleic acids, enhances cellular uptake, and enables efficient cytosolic delivery. Their clinical validation in infectious-disease messenger RNA (mRNA) vaccines has catalyzed rapid progress toward oncology applications. Preclinical and early-phase trials have indicated that mRNA-LNPs encoding tumor-associated antigens or patient-specific neoantigens can expand cytotoxic T cells and elicit preliminary antitumor activity. Key barriers remain. Manufacturing cost and batch consistency challenge scale-up. Physicochemical instability necessitates cold-chain logistics and complicates global deployment. Reactogenicity and anti-PEG antibodies increase safety and dosing concerns. Within tumors, immunosuppressive microenvironments, heterogeneous antigen expression, and suboptimal lymphoid targeting limit the efficacy of vaccines. This review describes the advances in LNP design (ionizable and biodegradable lipids, PEG alternatives, ligand-mediated targeting), formulation strategies (thermostable and lyophilized systems), and delivery routes (intranodal and intratumoral) to overcome these bottlenecks. It also highlights synergistic combinations with checkpoint blockade, radiotherapy, and innate agonists, and examines emerging pipelines leveraging AI-guided neoantigen discovery and quality control. By integrating material engineering, immunology, and translational evidence, we identified failure points and proposed a roadmap for next-generation LNP-based cancer vaccines. The goal is to accelerate progress from bench to clinic, while improving manufacturability, access, and durable patient benefits.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100484"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977960","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":"A pH-responsive dual-drug nanoplatform for stromal remodeling and enhanced chemotherapy via MMP3/TGF-β inhibition","authors":"Tao Tan ,&nbsp;Yihan Wang ,&nbsp;Ran Cheng ,&nbsp;Dongsheng Yang","doi":"10.1016/j.ijpx.2026.100489","DOIUrl":"10.1016/j.ijpx.2026.100489","url":null,"abstract":"<div><div>The dense, fibrotic extracellular matrix (ECM) generated by cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) presents a formidable physical barrier that severely limits the penetration and efficacy of chemotherapeutic agents. This study aimed to design and validate a pH-responsive, dual-drug nanosystem (RPAE-QM) capable of overcoming this stromal resistance by coordinated delivery of a stromal-modulating agent and a potent cytotoxic payload. The RPAE-QM nanosystem was constructed to co-encapsulate the stromal-modulating agent quercetin (Que) and the chemotherapeutic drug DM1. RPAE-QM exhibited significant pH-responsive drug release, leading to strong synergistic cytotoxicity and superior tumor destruction capability in 3D spheroid models. Mechanistic investigation provided a definitive explanation for this efficacy. Molecular docking and molecular dynamics simulations predicted that Que. has high affinity and exceptional kinetic stability when binding to MMP-3. Subsequent experiments confirmed the downstream consequences of this interaction: treatment with Que. caused dose-dependent inhibition of both MMP-3 and TGF-<em>β</em>₁ secretion from CAFs. Moreover, this was accompanied by a significant, concentration-dependent reduction in the phosphorylation of Smad2/3, a key downstream effector of the TGF-<em>β</em> signaling pathway. The RPAE-QM nanosystem provides an effective dual-action strategy, simultaneously addressing the stromal barrier while delivering a potent cytotoxic agent. Mechanistically, our findings indicate that Que. suppresses the pro-fibrotic MMP3/TGF-<em>β</em>/Smad signaling axis in our CAF model. This work therefore introduces a dual-action therapeutic concept, offering a mechanistically-defined approach to disrupt stromal barriers and improve drug efficacy at the pre-clinical proof-of-concept stage.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100489"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978487","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":"Tumor-responsive PEGylated mesoporous nanoparticles achieve enhanced chemotherapy and reduced toxicity in prostate cancer","authors":"Yangyang Song ,&nbsp;Xue Tan ,&nbsp;Kai Yu ,&nbsp;Yue Wang ,&nbsp;Jixue Wang","doi":"10.1016/j.ijpx.2026.100492","DOIUrl":"10.1016/j.ijpx.2026.100492","url":null,"abstract":"<div><div>Docetaxel (DTX) remains the first-line chemotherapeutic for advanced prostate cancer, however, its therapeutic efficacy remains limited by poor aqueous solubility, rapid systemic clearance, and severe dose-dependent toxicity. To overcome these constraints, we developed a PEGylated, disulfide-bridged hierarchical mesoporous silica nanocarrier (PEG–HMS) as a redox-sensitive delivery system for DTX (PEG–HMS–DTX). The nanostructure was fabricated by integrating disulfide-containing organosilanes into the silica framework and conjugating thiol-reactive PEG chains, thereby combining long circulation stability with tumor-selective release. Comprehensive physicochemical characterization confirmed uniform spherical morphology, an optimal hydrodynamic size (∼40–50 nm), attenuated surface charge following PEGylation, and high colloidal stability in physiological media, while disulfide linkages enabled responsive structural changes under reductive conditions. Drug release was minimal under physiological conditions (&lt;30% at 72 h) but markedly accelerated in the presence of glutathione (∼60% at 72 h). Compared with free DTX or non-PEGylated carriers, PEG-HMS-DTX exhibited stronger cellular uptake and enhanced cytotoxicity in RM-1 prostate cancer cells. In tumor-bearing mice, PEG-HMS-DTX achieved superior tumor accumulation (peak at ∼12 h), pronounced tumor growth inhibition (&gt;70%), minimal systemic toxicity, and elevated apoptosis characterized by increased cleaved caspase-3 and reduced PCNA/Bcl-2 expression. Collectively, this “stable-in-circulation, trigger-in-tumor” platform substantially improves intratumoral DTX delivery and apoptosis-driven antitumor efficacy, while maintaining systemic safety. These findings highlight PEG-HMS-DTX as a promising and generalizable strategy for prostate cancer chemotherapy, warranting further pharmacokinetic, immunogenicity, and GLP toxicology studies to support translational advancement.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100492"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074026","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":"Photothermally-activated nano-delivery system for on-demand treatment of diabetic wound infections","authors":"Rong Huang ,&nbsp;Wenjia Yang ,&nbsp;Tao Wang ,&nbsp;Xianbin Cao ,&nbsp;Shiyu Sun ,&nbsp;Jiaxin Jiang ,&nbsp;Hongsheng Liu ,&nbsp;Jianzhong Peng","doi":"10.1016/j.ijpx.2025.100464","DOIUrl":"10.1016/j.ijpx.2025.100464","url":null,"abstract":"<div><div>Bacterial-infected diabetic wounds, characterized by a persistent hyperglycemic environment, susceptibility to secondary bacterial infections, and chronic inflammatory responses, often exhibit impaired healing processes, posing a significant challenge in clinical management. To address this issue, this study designed and constructed a near-infrared (NIR) light-activated intelligent hydrogel drug delivery system—LSZBP@CMO. This system integrates highly efficient photothermal conversion components with a pH-responsive CMO hydrogel based on Schiff base reactions, achieving a dual-stimuli responsive drug release mechanism governed by exogenous NIR light and endogenous microenvironmental acidity. Under NIR irradiation, localized mild hyperthermia is generated, leading to the disruption of thermosensitive structures within the system and exposure of nanoparticles. This process, synergizing with the mildly acidic environment, further triggers rapid drug release, significantly enhancing antibacterial efficacy. Both in vitro and in vivo experimental results demonstrated that LSZBP@CMO not only efficiently eliminates bacteria but also effectively alleviates oxidative stress, modulates the inflammatory microenvironment, and markedly promotes angiogenesis, collagen deposition, and epithelial regeneration. In a diabetic rat model with infected wounds, the treatment group exhibited outstanding repair performance, achieving a wound healing ratio of 97.39 ± 1.60 % by day 7. This study provides an actively controllable strategy with promising clinical application prospects for on-demand therapy of refractory bacterial-infected diabetic wounds.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100464"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765680","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":"Bioinspired and stimuli-responsive nanocomposites for targeted therapy in ovarian and endometrial tumors","authors":"Jihang Yao ,&nbsp;Lulu Liu ,&nbsp;Xiufei Teng ,&nbsp;Daming Chu ,&nbsp;Silu Ding ,&nbsp;Hui Li ,&nbsp;Hua Chang ,&nbsp;Jing Liu","doi":"10.1016/j.ijpx.2026.100493","DOIUrl":"10.1016/j.ijpx.2026.100493","url":null,"abstract":"<div><div>Ovarian and endometrial cancers pose significant therapeutic challenges due to late-stage diagnosis and resistance to traditional therapies. Recent progress in the development of multiscale, bioinspired, and stimuli-responsive nanocomposites presents promising avenues for targeted therapy. These nanocomposites, engineered across a range from micrometers to nanometers, utilize hierarchical structures to enhance drug delivery, reduce systemic toxicity, and improve therapeutic efficacy. Through the integration of nanoparticles, hydrogels, and polymeric nanocarriers, these materials can react to external stimuli such as pH, temperature, and magnetic fields, enabling precise and controlled release of therapeutic agents. This review examines the design principles of these sophisticated composites, concentrating on their capacity to replicate the tumor microenvironment and enhance targeting specificity in ovarian and endometrial cancers. Furthermore, it highlights current clinical obstacles, safety considerations, and the considerable potential of these materials in personalized gynecologic oncology, underscoring their efficacy at both macroscopic and nanoscopic levels.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100493"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164035","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":"Chitosan-based nanozyme hydrogels: Advanced antioxidant and sustained-release systems for the prevention and treatment of skin photoaging","authors":"Qucheng Huang ,&nbsp;Xiaojun Zhang ,&nbsp;YuanYuan Zuo ,&nbsp;Leiyi Wang ,&nbsp;Huan Sun ,&nbsp;Hewei Xu ,&nbsp;Miao Yu ,&nbsp;Chang Liu","doi":"10.1016/j.ijpx.2026.100491","DOIUrl":"10.1016/j.ijpx.2026.100491","url":null,"abstract":"<div><div>Photoaging of the skin is a chronic damage process caused by prolonged exposure to ultraviolet radiation, characterized by increased oxidative stress, activation of inflammatory responses, and collagen degradation. However, photoaging of the skin presents challenges in prevention, limited efficacy of therapeutic agents, and difficulties in repairing the damage. In recent years, chitosan-based hydrogels, which exhibit excellent biocompatibility, biodegradability, film-forming properties, and the ability to deliver sustained-release medication, have progressively emerged as cutting-edge therapeutic agents for treating photoaging of the skin. Nanozymes are nanomaterials possessing enzymatic functions that effectively scavenge reactive oxygen species generated by ultraviolet irradiation, exhibiting excellent antioxidant properties. Loading nanozymes into chitosan-based hydrogels not only combines the biocompatibility of chitosan hydrogels with the antioxidant properties of nanozymes to enhance therapeutic efficacy but also enables stable loading and controlled release of drugs and active ingredients. This further improves treatment efficiency while fully leveraging the moisturizing and restorative properties of the hydrogel matrix. This paper systematically summarizes the construction methods, performance optimization, and mechanism of action of chitosan-based nanozyme hydrogels in preventing and treating skin photoaging. It focuses on analyzing research advances in their capacity to scavenge free radicals, alleviate inflammation, and promote skin barrier repair, while exploring their application prospects and challenges in skin repair and the cosmetics sector.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100491"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977959","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":"3D-printed polypills for personalized medicine and precision oral drug delivery in pharmaceutical practice: A review","authors":"Mahesha Keerikkadu,&nbsp;Sathvik Chennamsetty,&nbsp;Akshay Shetty,&nbsp;Vamshi Krishna Tippavajhala,&nbsp;Mahalaxmi Rathnanand","doi":"10.1016/j.ijpx.2025.100474","DOIUrl":"10.1016/j.ijpx.2025.100474","url":null,"abstract":"<div><div>3D-printed polypills have considerably changed the way oral medications can be delivered. They offer a way to create a single dosage form that can be customized to meet the needs of individual patients, while also allowing multiple drugs to be stored in distinct compartments, layers, or designs. Using 3D printing techniques such as fused deposition modeling (FDM), inkjet printing, stereolithography (SLA), selective laser sintering (SLS), and Arburg Plastic Freeforming (APF), it is possible to create tablet structures that provide control over various aspects of dissolution and drug release through engineered porosity and density of the material used during fabrication. Several technologies have been developed to enable the fabrication of polypills, along with methods for selecting the correct excipients, controlling drug release through various mechanisms, and considering the principles of quality-by-design when creating a polypill. In recent years, new material innovations have significantly enhanced the ability of polypills to deliver drugs with improved mechanical strength, stability, and accuracy upon printing. The ability to provide personalized medication regimens for patients with chronic diseases requiring precise titration or a complex regimen is expected to have a great impact on the management of patients taking 3D-printed polypills. 3D-printed polypills have significant translational challenges due to inconsistent production, difficulty obtaining regulatory approval, the inability to scale up batch manufacture, and inadequate long-term stability of the final product.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100474"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921834","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":"ROS-triggered smart hydrogel adhesives for modulating the inflammatory microenvironment and promoting tendon-bone interface regeneration","authors":"Hebei He ,&nbsp;Yifen Lin ,&nbsp;Jia Fang ,&nbsp;Kai He ,&nbsp;Wenjun Li ,&nbsp;Min Du ,&nbsp;Shilong Lin ,&nbsp;Xiaofei Zheng ,&nbsp;Hanyu Lu","doi":"10.1016/j.ijpx.2026.100502","DOIUrl":"10.1016/j.ijpx.2026.100502","url":null,"abstract":"<div><div>Currently, suture surgery for rotator cuff repair is unable to regenerate the original functional fibrocartilage layer at the tendon-bone interface, resulting in high postoperative retear rates. In this study, a ROS-triggered smart hydrogel adhesive (DPQP@ME) was designed to synergistically enhance the functional repair of the tendon-bone interface during suture surgery by modulating the inflammatory microenvironment, promoting cell differentiation, and providing mechanically adaptive support. Metal-phenolic nanoparticles (ME) with multiple bioactivities were formed through the self-assembly of epigallocatechin gallate (EGCG) and Mg²⁺. Subsequently, ME, dithiothreitol (DTT), polyethylene glycol diacrylate (PEGDA), and boronic acid-modified quaternary ammonium chitosan (QCS-PBA) were crosslinked <em>via</em> borate ester bonds, thioether bonds, and photo-crosslinking to form a bioactive hydrogel adhesive with ROS responsiveness and favorable mechanical properties. Based on the ROS sensitivity of the borate ester bonds and thioether bonds, DPQP@ME exhibited favorable ROS-responsive drug release properties, with ME release reaching 73.15 ± 1.35% in H₂O₂-containing PBS <em>versus</em> 33.15 ± 1.65% in PBS alone. <em>In vitro</em> cellular experiments demonstrated that DPQP@ME could effectively reduce intracellular ROS levels, regulate macrophage polarization toward an anti-inflammatory phenotype, and promote osteogenic differentiation as well as cartilage formation. Animal studies further demonstrated that DPQP@ME significantly attenuated inflammatory responses and promoted functional reconstruction of the tendon-bone interface. In conclusion, this novel smart hydrogel adhesives provides a promising therapeutic strategy for tendon healing.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100502"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188931","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":"Comparing the efficacy of nanocarriers for cutaneous and follicular delivery of poorly water-soluble molecules: A case study with ciclosporin A","authors":"Aditya R. Darade ,&nbsp;Maria Lapteva ,&nbsp;Yogeshvar N. Kalia","doi":"10.1016/j.ijpx.2026.100505","DOIUrl":"10.1016/j.ijpx.2026.100505","url":null,"abstract":"<div><div>Therapeutic agents approved for the topical treatment of dermatological diseases have diverse physicochemical properties, but they are frequently poorly water-soluble, which makes it a challenge to prepare stable aqueous formulations with good delivery characteristics. Several types of nanocarrier have been reported to facilitate formulation and to enhance cutaneous delivery but there are few direct comparisons of nanocarriers in terms of their ability to deliver a specific molecule to the skin under the same controlled conditions. The present study aimed to address this by developing, optimizing, and comparing different nanocarriers with respect to their ability to deliver ciclosporin A (CsA) to the skin and the hair follicle. Nanoconstructs were categorized as vesicular carriers (micelles and liposomes), emulsion-based systems (microemulsions and nanoemulsions), and nanoparticle systems (e.g. polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers). Formulations were optimized using a design of experiments approach and were characterized with respect to size, morphology and incorporation efficiency. Cutaneous and follicular delivery experiments were performed using porcine skin. CsA deposition, cutaneous biodistribution, follicular delivery and targeting potential (ratio of delivery to skin with and without pilosebaceous units) were assessed. Nanoemulsions, kinetically stable systems with high thermodynamic activity, showed the highest cutaneous delivery of CsA among the nanosystems tested followed by solid lipid nanoparticles and mPEG-dihexPLA micelles – i.e. three different types of nanocarrier. The results confirmed the pivotal role of thermodynamic activity in determining delivery efficiency of a nanocarrier and its greater importance than other routinely studied morphological parameters such as nanocarrier size: the smallest nanocarriers did not yield the highest delivery.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100505"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188932","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}