Drug Delivery and Translational Research最新文献

{"title":"Cellulose and its potential applications in skin biology; a comprehensive review.","authors":"Aasia Hameed, Adnan Haider, Hussain Mustatab Wahedi","doi":"10.1007/s13346-026-02140-7","DOIUrl":"10.1007/s13346-026-02140-7","url":null,"abstract":"<p><p>Cellulose is the most abundant natural biopolymer obtained from plants, animals, and microbes. Cellulose is porous, biocompatible, biodegradable, noncytotoxic, and can retain water for a longer period. Therefore, cellulose has various applications in the medical, cosmetic, paper, and food industries. The current review summarizes the recent progress related to the application of cellulose in skin biology. Cellulose is preferable for skin biology applications due to its porosity, and hygroscopic nature that enables it to mimic the extracellular matrix (ECM) of native skin. Cellulose can be modified by combining with other biopolymers to make a functional cellulose composite. Researchers have developed various cellulose composites that are successfully used as wound dressing agents, scaffolds for skin tissue engineering, and vehicles for drug delivery like anticancer or other hydrophobic drugs. Cellulose-based facial masks act as a carrier for active agents like anti-aging, anti-wrinkle, and anti-acne substances. Cellulose can also be used as a stabilizer in the preparation of emulsion-based creams and other cosmetic products. It is concluded that cellulose is a suitable biopolymer in the global marketplace for skin applications, but further advancements should be made to maximize its clinical use.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2660-2677"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation considerations in enhancing olfactory mucosal deposition for nose-to-brain drug delivery.","authors":"Anisha A DSouza, Maayan Kahan, Alicia Yang, Smrithi Padmakumar, Benjamin S Bleier, Mansoor M Amiji","doi":"10.1007/s13346-026-02097-7","DOIUrl":"10.1007/s13346-026-02097-7","url":null,"abstract":"<p><p>Nose-to-brain (N2B) drug delivery offers a promising alternative to circumvent the blood-brain barrier and deliver therapeutic agents directly to the central nervous system. Among the intranasal pathways, targeting the olfactory mucosa is particularly attractive due to its direct anatomical and functional connection to the brain. However, effective deposition and retention of drug-loaded formulations in the olfactory region remain significant challenges, owing to complex nasal anatomy, mucociliary clearance, and limited surface area. This review critically examines the physiological and anatomical barriers to olfactory targeting and highlights recent advances in nanoparticle-based strategies designed to enhance mucosal deposition and transport. Various formulation approaches-including mucoadhesive polymers, surface-functionalized nanocarriers, and stimuli-responsive systems-are discussed alongside innovative delivery devices and administration techniques tailored for olfactory mucosal delivery. In vitro, ex vivo, and in vivo models used to evaluate these strategies are reviewed, as are safety, regulatory, and translational considerations. Finally, the review explores emerging technologies such as patient-specific delivery platforms and smart nanoparticles, offering a forward-looking perspective on the future of N2B therapeutics for neurological disorders.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2552-2577"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-line 3D-printed intravaginal ring for nonhormonal contraception.","authors":"Sarah Anne Howard, Maimoona S Bhutta, Rima Janusziewicz, Andrés Prieto Trujillo, Ava L Cohen, Gustavo F Doncel, S Rahima Benhabbour","doi":"10.1007/s13346-025-02038-w","DOIUrl":"10.1007/s13346-025-02038-w","url":null,"abstract":"<p><p>With nearly half of all pregnancies occurring unintended, effective and acceptable contraceptive options remain a global necessity. Though contraceptives with extended durations of action reduce the need for strict daily adherence, thus enhancing compliance and reliability, only one of these methods - the copper intrauterine device (IUD) - prevents pregnancy without administering exogenous hormones. Herein, we demonstrate co-delivery of two nonhormonal contraceptive agents, lactic acid (LA) and glycerol monolaurate (GML), using a next-generation 3D-printed intravaginal ring (IVR). Through alterations in ring properties and drug loading, a range of LA and GML release rates were achieved in vitro, demonstrating the flexibility of the platform technology. Rings elicited sustained release of LA and GML at target release rates over 30 days or longer. Additionally, these studies explored how drugs with different physiochemical properties interact within the IVR matrix and further elucidated IVR drug loading and release mechanisms.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2956-2975"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bionic platelet membrane-coated rutin nanoparticles attenuate ulcerative colitis by suppressing platelet-mediated macrophage inflammation.","authors":"Rong Zhang, Ruya Mei, Bingqing Liang, Xinyue Zhang, Tong Zhang, Jie Luo, Juhua Zhang, Qin Pan, Yuzhong Yan","doi":"10.1007/s13346-025-02028-y","DOIUrl":"10.1007/s13346-025-02028-y","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic, immune-mediated disorder with limited treatment efficacy due to drug resistance. As key immune effectors, Macrophages drive UC pathogenesis: The M1 polarization promoted through P-selectin/PSGL-1 binding between platelets and macrophages exacerbates inflammation. Rutin-PEG-PLGA nanoparticles (P@Rut) were engineered by encapsulating rutin in PEG-PLGA cores. Biomimetic platelet membrane nanoparticles (PP@Rut) were synthesized by extracting platelet membranes and coating P@Rut. The blockade of platelet-macrophage interactions by PP@Rut was assessed in vitro and in vivo. The inhibition of macrophage polarization and JNK/STAT1 pathway was evaluated via immunofluorescence (CD86/CD206) and RT-qPCR (IL-1β, TNF-α, TGF-β). Apoptosis was quantified using flow cytometry and TUNEL staining, complemented by Western blot analysis of apoptosis-related proteins(Bcl-xl, Bak, and cleaved-caspase3). Additionally, intestinal barrier integrity was assessed through tight junction protein expression (Occludin, Claudin-1, ZO-1), while therapeutic efficacy was determined via colon length, body weight, disease activity index (DAI) scores, and H&E staining histopathological analysis. PP@Rut significantly shifted macrophage polarization from M1 to M2 through the JNK/STAT1 pathway, suppressed inflammatory response, reduced mucosal epithelial cells apoptosis, and improved intestinal barrier integrity. In DSS-induced mice, PP@Rut demonstrated higher accumulation in inflamed colon versus P@Rut, ameliorating body weight loss, DAI scores, colon shortening, and histopathological injury, including the reduction in inflammatory infiltration and crypt damage. PP@Rut represents a synergistic nanotherapeutic strategy that competitively inhibits platelet-macrophage binding to reprogram polarization, suppress inflammation, and restore barrier function in UC.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2824-2845"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel crystalline solid dispersions to improve the oral bioavailability and anti-liver cancer effect of Sorafenib.","authors":"Yong Zhang, Yujin Wang, Baihui Gong, Weiqi Liu, Jun Wang, Chunhui Hu","doi":"10.1007/s13346-025-02018-0","DOIUrl":"10.1007/s13346-025-02018-0","url":null,"abstract":"&lt;p&gt;&lt;p&gt;This study investigates the interrelationships among drug loading, steric hindrance (S&lt;sub&gt;h&lt;/sub&gt;), defined as the spatial constraints imposed by the crystallized polymer network that physically restrict drug crystal growth, effective glass transition temperature (T&lt;sub&gt;g&lt;/sub&gt;&lt;sup&gt;ᴱ&lt;/sup&gt;), and drug particle size in crystalline solid dispersion (CSD) systems. Furthermore, we examine how CSD formulations enhance dissolution rates, oral bioavailability, and anti-liver cancer efficacy through comprehensive in vitro and in vivo studies. SOR-P188-CSD with different drug loadings were synthesized via spray drying, utilizing Sorafenib (SOR) as the model drug and poloxamer 188 (P188) as the carrier. The association between S&lt;sub&gt;h&lt;/sub&gt;/T&lt;sub&gt;g&lt;/sub&gt;&lt;sup&gt;E&lt;/sup&gt;, drug particle size, and dissolution behavior of CSDs was investigated by probing the crystalline domain (particle size), crystallization kinetics, and interaction dynamics within the CSD matrices. Notably, the particle size of SOR within SOR-P188-CSD exhibited a significant reduction compared to the pure drug. Analysis of crystallization kinetics unveiled a two-step crystallization mechanism for SOR-P188-CSD, where P188 crystallization preceded that of SOR. Intriguingly, an intermolecular interaction between SOR and P188 was observed, exerting an inhibitory effect on the crystallization kinetics of both components. This inhibitory effect escalated concomitantly with increasing drug loading. Within the SOR-P188-CSD system, P188 within formulations featuring low drug loading orchestrated a reduction in drug particle size by modulating the transverse and longitudinal growth rates of SOR, with S&lt;sub&gt;h&lt;/sub&gt; serving as the primary influencing factor. Conversely, in formulations with high drug loading, T&lt;sub&gt;g&lt;/sub&gt;&lt;sup&gt;E&lt;/sup&gt; of CSD interacted with temperature to regulate crystal nucleation and growth rates, thereby reducing drug particle size, with T&lt;sub&gt;g&lt;/sub&gt;&lt;sup&gt;E&lt;/sup&gt; emerging as the principal influencing factor. Subsequent in vitro and in vivo dissolution studies demonstrated a marked enhancement in the dissolution rate and bioavailability of drugs encapsulated within SOR-P188-CSD formulations compared to the active pharmaceutical ingredient (API). In the nude mouse liver cancer xenograft model, SOR-P188-CSD can significantly inhibit tumor growth by suppressing the expression of angiogenesis related factors (CD31, CD34, VEGF), tumor proliferation related factors (Ki67), and iron death related protein (GPX4). Collectively, our findings underscore the pivotal role of S&lt;sub&gt;h&lt;/sub&gt;/T&lt;sub&gt;g&lt;/sub&gt;&lt;sup&gt;E&lt;/sup&gt; in modulating drug particle size within CSD matrices through distinct mechanisms. Furthermore, our study underscores the potential of P188-mediated CSD formulations in augmenting the dissolution rate and bioavailability of poorly soluble drugs by minimizing drug particle size and sustaining drug supersaturation, thereby enhancing the efficacy of sorafenib in treating liver cancer.&lt;/p","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2751-2772"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and characterization of exenatide-loaded PLGA microspheres prepared by coacervation.","authors":"Cameron White, Steven P Schwendeman","doi":"10.1007/s13346-025-02008-2","DOIUrl":"10.1007/s13346-025-02008-2","url":null,"abstract":"<p><p>Bydureon^® is a once-weekly injection of poly(lactide-co-glycolide) (PLGA) microspheres containing exenatide acetate, a synthetic analog of the GLP-1 receptor agonist exendin-4. These microspheres are formulated by coacervation (i.e., phase separation), using a single-emulsion method. There remains a knowledge gap between how formulation variables affect product attributes and performance. We aimed to bridge this gap by evaluating the effect of formulation variables on encapsulating exenatide in PLGA microspheres at similar compositions to Bydureon^®. We first screened process variables without peptide to establish stability windows during coacervation, i.e., conditions that produced high yields of well-formed microspheres. We introduced exenatide during coacervation as a function of PLGA concentration, DCM (dichloromethane): water and DCM: Si oil (polydimethylsiloxane) volume ratios, hold time between Si oil addition and heptane bath immersion, and other manufacturing conditions. We evaluated the formulation yield, residual solvent content, encapsulation efficiency, and 24-h release. A PLGA concentration of 6% w/w was selected because of its wide range of stable formulations with varying DCM: Si oil phase volume ratios. The hold time between Si oil addition and heptane immersion was set at 1 min, although microspheres were stable between a range of 10 s to 2 min. The resultant formulations displayed elevated yields of > 50%, and a low in-vitro 24-h burst release of 2-6%. These formulations exhibited continuous release profiles of predominantly parent and glycolic acid acylated peptide for over 56 days in vitro, as expected by the commercial product. The framework of conditions and their effects on the formulations was established for loading exenatide in PLGA microspheres with desirable release characteristics. These results are useful for both microencapsulation of generic and new peptides in PLGA microspheres by coacervation.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2697-2710"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine and guanosine-based oligonucleotides-loaded PLGA nanoparticles attenuates progression of surgically induced osteoarthritis.","authors":"Yoonhee Kim, Jin Han, Ji Young Park, Seungwoo Han","doi":"10.1007/s13346-025-02020-6","DOIUrl":"10.1007/s13346-025-02020-6","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a chronic degenerative joint disease that lacks effective therapies to halt its progression. While endogenous purinergic signaling-particularly via adenosine-shows promise for reducing inflammation, it is limited by short half-life and off-target effects. To address these limitations, we developed an optimal anti-inflammatory adenosine-guanosine-based oligonucleotide encapsulated in poly(lactic-co-glycolic) acid (PLGA)-based nanoparticles (NanoOligo) to enhance in vivo stability and investigated its impact on surgically induced OA models and the underlying mechanisms responsible for its anabolic effects. A large oligonucleotide library (482 unique 10- to 20-mer sequences) was screened in RAW264.7 macrophages under LPS-induced inflammation to identify the most potent candidate, which was then encapsulated into PLGA nanoparticles using a microfluidic system. NanoOligo significantly protected against cartilage degeneration and alleviated pain behaviors in the rat ACLT + pMx model following intra-articular administration. In IL-1β-treated chondrocytes, it markedly suppressed inflammatory cytokines (TNFα, IL-6) and catabolic proteases (MMP-3, MMP-13, ADAMTS5). Mechanistically, NanoOligo's anti-catabolic effects were dependent on A1R and A2AR, leading to activation of the PKA-CREB axis and suppression of p38 MAPK signaling, which in turn reduced oxidative stress and cellular senescence via upregulation of the Sirt1-Nrf2-HO-1 antioxidant pathway. Collectively, these findings support joint-localized purinergic modulation as a potential therapeutic target for OA treatment, aligning structural protection with improvements in pain-related behaviors.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2773-2787"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smart nanocarriers in triple-negative breast cancer: recent advances in targeting and translational application.","authors":"Aparana Mishra, Vitthal L Gole, Smriti Ojha","doi":"10.1007/s13346-025-02022-4","DOIUrl":"10.1007/s13346-025-02022-4","url":null,"abstract":"<p><p>Breast cancer remains one of the most prevalent causes of cancer-related mortality worldwide. Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that has a poor prognosis and limited therapeutic options. Smart nanocarriers have been developed through significant advancements in nanotechnology over the past few years. To increase therapeutic effectiveness while reducing systemic toxicity, recent developments in nanotechnology have led to the creation of smart nanocarriers-nanosystems designed to carry drugs in a targeted, stimulus-responsive manner. Liposomes, dendrimers, micelles, carbon nanotubes, and polymeric nanoparticles are among the most common types of smart nanocarriers discussed in this study. Their design principles and functional features characterize the many forms of smart nanocarriers. Targeting techniques specific to breast cancer are highlighted, with a particular focus on active targeting via ligands and tumor microenvironment-responsive systems applicable to TNBC. By examining the integration of biodegradable materials, green synthesis methods, and alignment with the global Sustainable Development Goals (SDGs), the study also underscores the crucial role of sustainability in nanomedicine. Significant advancements have been made, but several biological, regulatory, and therapeutic issues still hinder the practical application of nanomedicine in treating TNBC. This review highlights key translational roadblocks and proposes strategic solutions to bridge the gap between the bench and the bedside.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2527-2551"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assemblies from prodrugs composed of antimicrobial peptides: a revolution in local lung cancer treatment, with microbiota as a main actor.","authors":"Abdallah Ladaycia, Laurent Lemaire, Hélène Pailhoriès, Nolwenn Lautram, Florence Franconi, Pascal Pigeon, Gérard Jaouen, Catherine Passirani, Elise Lepeltier","doi":"10.1007/s13346-025-02037-x","DOIUrl":"10.1007/s13346-025-02037-x","url":null,"abstract":"<p><p>Human microbiota is now recognized as a fundamental organ of the body. In its healthy state, it fulfills essential local and systemic functions, whereas dysbiosis disrupts these roles and can contribute to disease. Although numerous studies have examined the relationship between microbiota and cancer, often revealing conflicting mechanisms and outcomes, this work has focused almost exclusively on the gut, leaving the lung microbiota largely unexplored. In this project, a ferrocifen compound was selected as an anticancer agent for lung cancer therapy. We found that lung microbiota actively degraded the ferrocifen. To prevent this degradation, the antibacterial peptide buforin II was synthesized, purified, and characterized. After confirming its antimicrobial activity, it was covalently conjugated to the ferrocifen, yielding an amphiphilic bioconjugate. This prodrug was subsequently formulated into self-assembled structures to enhance ferrocifen solubility and bioavailability. The resulting self-assemblies were evaluated in an orthotopic murine model of lung cancer and administered via nebulization to assess their therapeutic efficacy. A significant reduction in tumor progression and an improved predicted survival in mice were obtained. Together, these findings highlight the capacity of the lung microbiota to interfere with anticancer therapies and underscore the importance of considering this flora when designing treatment strategies for lung cancer.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2937-2955"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational design of lipid-based nanoparticles for targeted anticancer therapies.","authors":"María Arenas-Moreira, Alberto Ocaña, Carlos Alonso-Moreno, Iván Bravo","doi":"10.1007/s13346-026-02110-z","DOIUrl":"10.1007/s13346-026-02110-z","url":null,"abstract":"<p><p>Targeted anticancer therapies, including monoclonal antibodies, antibody-drug conjugates, siRNA, small-molecule inhibitors, and PROTACs, offer precise treatments but face severe pharmacokinetic and biological barriers, such as poor bioavailability, limited tumor penetration, and off-target toxicity. While first-generation lipid-based nanoparticles (LBNPs) successfully utilized the enhanced permeability and retention (EPR) effect, relying exclusively on passive targeting is insufficient due to tumor heterogeneity. Therefore, this review provides an integrative analysis focused on the rational design of LBNPs. We systematically explore how the distinct structural complexities and biological barriers of each therapeutic modality strictly dictate specific LBNP design rules. The optimization of various nanocarriers-including liposomes, solid-lipid nanoparticles, and nanostructured lipid carriers-is discussed through customized lipid compositions, surface functionalization for active targeting, and the incorporation of ionizable lipids to overcome intracellular barriers like endosomal entrapment. Furthermore, these structural designs are correlated with optimal administration routes, and the impact of formulation methods is evaluated by contrasting traditional emulsification with advanced continuous platforms like microfluidics and supercritical fluid technology. Finally, the clinical landscape and translational challenges of approved and experimental nanomedicines are assessed. We conclude that the transition from bench to bedside is currently hindered less by preclinical efficacy and more by manufacturing and regulatory bottlenecks. Overcoming chemistry, manufacturing, and controls (CMC) challenges, ensuring robust industrial scalability, and establishing harmonized regulatory frameworks are critical priorities for the future clinical success of targeted nanomedicines.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2578-2602"},"PeriodicalIF":6.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}