International Journal of Pharmaceutics最新文献

{"title":"Harnessing unique architecture and emerging strategies of solid lipid nanoparticles to combat colon cancer: A state-of-the-art review","authors":"Ashutosh Gupta ,&nbsp;Sandesh Ramchandra Jadhav ,&nbsp;Viola Colaco ,&nbsp;Moumita Saha ,&nbsp;Amartya Ghosh ,&nbsp;Amatha Sreedevi ,&nbsp;Deepanjan Datta ,&nbsp;Srinivas Hebbar ,&nbsp;Sudheer Moorkoth ,&nbsp;Virendra S. Ligade ,&nbsp;Namdev Dhas","doi":"10.1016/j.ijpharm.2025.125562","DOIUrl":"10.1016/j.ijpharm.2025.125562","url":null,"abstract":"<div><div>Cancer is a serious worldwide public health problem, ranking as the second leading cause of death in the United States. The third most prevalent tumor kind in the world is a colon or rectal tumor. Colon Cancer (CC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths globally. In the US, CC has become the 2nd most common cause of death after having different advancements like detection, surgery, and chemotherapy. The current strategies for treating colon cancer have several disadvantages, including higher toxicity, drug resistance, damage to healthy cells, solubility, specificity, a lower therapeutic index, and more. Solid lipid nanoparticles (SLNs) are a viable targeted treatment option for colon cancer to avoid this problem. This comprehensive review discussed the severity, pathophysiology, risk factors, and stages of colon cancer. The review covers the most effective colon cancer therapy and diagnostic procedures, including HSgFOBT, Fecal immunological test (FIT), Colonoscopy, FIT-DNA Test/mt-sDNA screening test, Colon capsule (CCE), Blood-based DNA Tests, and Flexible sigmoidoscopy. This review<!--> <!-->emphasizes the need for novel and specific approaches to colon cancer treatment to improve patient outcomes.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125562"},"PeriodicalIF":5.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803208","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":"Thermoresponsive engineered emulsions stabilised with branched copolymer surfactants for nasal drug delivery of molecular therapeutics","authors":"Abhishek Rajbanshi ,&nbsp;Eleanor Hilton ,&nbsp;Emily Atkinson ,&nbsp;James B. Phillips ,&nbsp;Shiva Vanukuru ,&nbsp;Vitaliy V. Khutoryanskiy ,&nbsp;Adam Gibbons ,&nbsp;Sabrina Falloon ,&nbsp;Cecile A. Dreiss ,&nbsp;Darragh Murnane ,&nbsp;Michael T. Cook","doi":"10.1016/j.ijpharm.2025.125506","DOIUrl":"10.1016/j.ijpharm.2025.125506","url":null,"abstract":"<div><div>Novel branched copolymer surfactants (BCS) allow the formation of oil-in-water emulsions that exhibit a temperature-induced liquid-to-gel transition. If the temperature of this transition is between room and body temperature (ca 25 and 37 °C, respectively), then the emulsions form a gel <em>in situ</em> upon contact with the body. A major advantage of this <em>in situ</em> gelation is the potential to manipulate the materials at room temperature in the low viscosity liquid state, then administer them to the body to initiate a switch to a retentive gel state, which could be used to deliver drugs to challenging sites such as the nasal mucosa. There are, however, several important factors which have not been explored for thermoresponsive BCS-stabilised emulsions to progress their use towards this application. Neither the delivery of drugs from the materials, the retention on tissue, nor the impact of co-formulated drugs on the thermoresponsive behaviours, are known. Furthermore, it has not been demonstrated that the materials are compatible with devices to generate sprays of the correct profiles for nasal administration. In this study we investigate the potential of thermoresponsive BCS-stabilised emulsions for the nasal delivery of licensed molecular therapeutics to examine the potential of BCS emulsion systems as a carrier for medicines. It was found that thermoresponsive behaviours can be maintained in the presence of drug substances, and that the liberation of the incorporated drugs occurs in a sustained manner. The BCS appear to have comparable cytotoxicity to common excipients and significantly enhanced retention on nasal tissue compared to even well-established mucoadhesives. The emulsions were incorporated into a spray device to demonstrate that the materials can be atomised with a plume appropriate for nasal administration prior to in situ gelation.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125506"},"PeriodicalIF":5.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795477","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":"Focus on therapeutic peptides and their delivery","authors":"E. Rosson ,&nbsp;F. Lux ,&nbsp;L. David ,&nbsp;Y. Godfrin ,&nbsp;O. Tillement ,&nbsp;E. Thomas","doi":"10.1016/j.ijpharm.2025.125555","DOIUrl":"10.1016/j.ijpharm.2025.125555","url":null,"abstract":"<div><div>Peptides are bioactive intermediates between small organic molecules and large biological compounds like antibodies or proteins. These compounds play a unique and valuable role as therapeutic agents, owing to their unique biochemical properties and versatility in treating a wide range of diseases such as metabolic disorders, cancer therapy, antimicrobial and anti-inflammatory agents. The global peptide therapeutics market is projected to exceed USD 50 billion by 2024, reflecting the increasing demand and interest in this field. Therapeutic peptides offer an optimal balance of specificity, safety, and molecular size, providing greater precision in targeting specific receptors with fewer off-target effects and reduced toxicity compared to small-organic drugs. Peptides also exhibit enhanced tissue penetration and present simpler, cheaper manufacturing processes with lower immunogenicity. To date, around 100 peptides have attained clinical approval in major markets, with nearly half of these approvals occurring in the past 20 years. This trend highlights the growing importance and therapeutic potential of peptides in modern medicine, explaining the substantial market associated with these treatments. The review presents a detailed comparison of the major parenteral administration modes for therapeutic peptides, specifically subcutaneous and intravenous routes. We highlight how these methods impact the pharmacokinetic profiles of peptides and influence patient outcomes, providing critical insights into the advantages and limitations of each route. Finally, a significant aspect of this review is its focus on innovative drug delivery systems and formulations designed to address the challenges of peptide delivery, namely stability, bioavailability, and therapeutic efficacy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125555"},"PeriodicalIF":5.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803191","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":"Anti-ageing Potential of Metformin Loaded Fennel Oil-Based Nanoemulgel: A Promising Novel Approach for Ultraviolet B-Induced Ageing","authors":"Ramsha Ansari ,&nbsp;Uzma Farooq ,&nbsp;Ahsan Ali,&nbsp;Mohd Haider Abbas,&nbsp;Fairy,&nbsp;Chaudhary Abdur Rehman Hamidullah,&nbsp;Pooja Jain,&nbsp;Mohd Aamir Mirza,&nbsp;Zeenat Iqbal","doi":"10.1016/j.ijpharm.2025.125559","DOIUrl":"10.1016/j.ijpharm.2025.125559","url":null,"abstract":"<div><h3>Background</h3><div>Ageing produces structural alteration of skin tissue when exposed to UV radiation, pollution and smoking, resulting in functional decline and mortality of the cells. The proposed study aimed at developing a commercially scalable fennel oil (FO) based metformin-loaded nanoemulsion (MTF-NE) incorporated in the hydrogel (MTF-HYD-NEG) providing anti-ageing effect.</div></div><div><h3>Methodology</h3><div>The scalable development of phytocompound incorporated nanoemulsion was done using a multi-step process involving excipient screening, optimization of nanoemulsion and thermodynamic stability assessment. The MTF-NE was developed using aqueous titration method containing Tween 80 as the surfactant and Transcutol P as the co-surfactant. The optimized nanoemulsion was incorporated into a hydrogel to form MTF-HYD-NEG. The formulation was characterized based on globule size, polydispersity index (PDI), zeta potential, spreadability, viscosity, and permeability. <em>In vitro</em> drug release and <em>ex vivo</em> permeation studies were conducted to assess sustained drug release. Confocal laser scanning microscopy (CLSM) was used to evaluate skin penetration. The <em>in vivo</em> studies were conducted using UV-B radiation induced mice models and old mice models to assess the anti-ageing efficacy through histopathological analysis, immunohistochemistry (MMP-1 expression), and biochemical assays (GSH, SOD, CAT, and MDA levels).</div></div><div><h3>Result and Discussion</h3><div>The characterization of the optimized MTF-NE exhibited a monodispersed pattern with an average globule size of 261.1 nm, PDI of 0.1305 and zeta potential of −4.4 mV. The MTF-NE was then converted into a hydrogel. The permeability of the MTF-HYD-NEG was assessed by <em>in vitro</em> release and <em>ex vivo</em> permeation studies that demonstrated a sustained release effect of Metformin (MTF) with the value of 71.565 ± 4.995 % over 24 hours and 4.503 ± 2.669 mg/cm² over 8 hours of study. Additionally, the release profile was further validated by the confocal microscopy through the mice’s skin tissue. The mean intensity was observed to be 53.472 which was retained at 4.472 at 50 µm depth of permeation demonstrating the better penetration of the nanocarrier. The data displayed by histopathology and MMP-1 expression by immunohistochemistry showed recuperation in the dermal tissue of the mice model seen in the post-treatment group of MTF-HYD-NEG in comparison to the control group and conventional treatment groups and depletion in MMP-1 production, improved dermal collagen and diminished wrinkles.</div></div><div><h3>Conclusion</h3><div>The results of the MTF-HYD-NEG formulation displayed enhanced permeability with a prolonged effect, depicting a reduction in MMP-1 expression, which could serve as a promising anti-ageing and antioxidant preparation attributed to the presence of a fennel oil base.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125559"},"PeriodicalIF":5.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795401","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":"Elastic osmotic capsules mimic bolus injection with high release at delayed burst","authors":"Veronica Hidalgo-Alvarez ,&nbsp;Kerr D.G. Samson ,&nbsp;Vasiliki Kolyva ,&nbsp;Yadunand Mani Koth ,&nbsp;Cameron I. Cumming ,&nbsp;Alex G. Leman ,&nbsp;Lindsey A. Waddell ,&nbsp;Vicki Stone ,&nbsp;Jayne C. Hope ,&nbsp;Ferry P.W. Melchels","doi":"10.1016/j.ijpharm.2025.125550","DOIUrl":"10.1016/j.ijpharm.2025.125550","url":null,"abstract":"<div><div>The need for repeated administration of vaccines is costly, logistically challenging and leads to reduced compliance. Osmosis-driven swelling and rupture has been proposed as a mechanism for delayed burst release to mimic follow-up (booster) injections without requiring further intervention. The use of microparticles does not guarantee a single bolus release, and previous studies using monolithic implants failed to demonstrate high instant release at the moment of burst. In this study we developed elastic capsules based on a caprolactone-lactide copolymer that released 75 ± 8 % of their contents instantly after up to several weeks of incubation. Capsules swelled up to 5x their original mass through highly reproducible osmosis-induced water uptake. The water uptake rates depended on osmotic strength and could be approximated with a numerical model revealing a water permeability of 3.6 ± 0.2 mm²/(Pa∙day) for all 118 capsules. The moment of burst depended on osmotic strength and capsule stiffness (median times varied from 16 to 37 days) and showed large scatter. The capsule material was non-toxic to a macrophage cell line and degraded through bulk hydrolysis, with an extrapolated completion time of 8 months. The capsules were administered successfully in bovine cadavers with a widely used applicator.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125550"},"PeriodicalIF":5.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795406","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":"MMP-responsive nanodrug loaded with glibenclamide for targeted repair of acute spinal cord injury","authors":"Ze Zhuang ,&nbsp;Bo Li ,&nbsp;Chaoyang Cai ,&nbsp;Yunheng Jiang ,&nbsp;Juliang Tang ,&nbsp;Limin Rong ,&nbsp;Bin Liu","doi":"10.1016/j.ijpharm.2025.125526","DOIUrl":"10.1016/j.ijpharm.2025.125526","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a severe traumatic neurological disease characterized by quadriplegia and paraplegia, leading to high rates of disability and mortality. The treatment of SCI remains a tremendous challenge due to limited medicine distribution to the lesion site and difficulty in permeating the blood-spinal cord barrier (BSCB). To overcome these issues, a novel polymer-based nanodrug delivery system was developed. After SCI, the matrix metalloproteinases (MMPs) increase rapidly around the injured site. By incorporating activated cell-penetrating peptides (ACPP), which specifically target MMP-2 and MMP-9 into the polyethylene glycol-polycaprolactone (PEG-PCL), a nano delivery system PEG-PCL-ACPP was created. Glibenclamide, a widely employed hypoglycemic drug, has been recognized for its ability to mitigate secondary injury in SCI. In this study, it was encapsulated within the PEG-PCL-ACPP to achieve targeted delivery and sustained release in the affected area. The therapeutic effects and mechanisms of Gliben@PEG-PCL-ACPP were investigated through both in <em>vitro</em> and in <em>vivo</em> experiments. These experiments verified that Gliben@PEG-PCL-ACPP exhibited favorable biocompatibility and its successful targeting of the affected region. Furthermore, it not only significantly reduced the progressive hemorrhagic necrosis (PHN), but also demonstrated anti-inflammatory and neuroprotective effects. Consequently, Gliben@PEG-PCL-ACPP has great potential for clinical application in SCI treatment.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125526"},"PeriodicalIF":5.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795468","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":"Pharmacometabolomics: An emerging platform for understanding the pathophysiological processes and therapeutic interventions","authors":"Chandra Prakash,&nbsp;Pronami Moran,&nbsp;Rohit Mahar","doi":"10.1016/j.ijpharm.2025.125554","DOIUrl":"10.1016/j.ijpharm.2025.125554","url":null,"abstract":"<div><div>Pharmacometabolomics has emerged as a new subclass of metabolomics, aiming to predict an individual’s response to a drug or optimize therapy based on prior information on an individual’s metabolic profile. Pharmacometabolomics is being explored in drug discovery, biomarker identification, disease diagnosis, monitoring of disease progression, and therapeutic intervention. The time points-based sample collection is essential to measure the response of individuals to pathophysiological processes and therapeutic interventions. Analytical techniques such as NMR, LC-MS, and GC–MS have been employed to assess a huge number of metabolites present in biological systems. NMR has an advantage over other analytical techniques as it provides a snapshot of tissue and biological fluids, however, it requires higher magnetic fields to achieve better resolution. GC–MS could cover a wide range of metabolites due to high resolution but requires derivatization for certain metabolites. LC-MS is equally competitive and separates a wide range of metabolites with diverse polarities but requires extensive method development. Several platforms have been developed to analyze the analytical data and provide meaningful results <em>via</em> data reduction methods. PCA and PLS-DA are the most common methods for reduction dimensionality through simplified multivariate data modeling. This manuscript brings insights into the overview of pharmacometabolomics experimental design and the application of various analytical techniques and multivariate statistical analysis in the various fields of medical research.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125554"},"PeriodicalIF":5.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795472","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":"Polymer-lipid hybrid microcarriers for oral codelivery of paclitaxel and tributyrin: development, optimization, and cytotoxicity in cells and spheroids of colorectal cancer","authors":"Claudio Fukumori ,&nbsp;Rodrigo Ken Kawassaki ,&nbsp;Regina G. Daré ,&nbsp;Luciana B. Lopes","doi":"10.1016/j.ijpharm.2025.125549","DOIUrl":"10.1016/j.ijpharm.2025.125549","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the third most frequent cancer worldwide. Despite advances in treatment, conventional chemotherapy suffers from severe side effects and limited drug selectivity, highlighting the importance of alternative therapies. In this study, a polymer-lipid hybrid microcarrier was developed for oral co-administration of paclitaxel (PTX) and tributyrin (TB) as a novel approach for CRC therapy. The microcarrier was designed with a pH-sensitive polymeric shell that encapsulates drug-loaded nanostructured lipid carriers (NLC); shell dissolution at intestinal pH enables localized release of the NLC. The methodological approach employed an emulsion of vegetable oil and NLC as a template for polymer deposition. Multiple parameters were optimized, including polymers ratios, NLC dilution, acid concentration, and sonication time. Spherical hybrid particles with smooth surface and mean size of 1000 nm were obtained; PTX encapsulation efficiency was 99.9 ± 0.2 %, with a production yield of 97.2 ± 0.08 %. Drug release followed the Korsmeyer-Peppas kinetic model. Cytotoxic evaluation in human colorectal adenocarcinoma HCT-116 monolayers showed that PTX encapsulation increased cytotoxicity, lowering IC₅₀ to 83.7 nM compared to 199.5 nM for free PTX. The addition of TB further improved cytotoxicity, reducing the IC₅₀ to 60.8 nM. A similar potentiation cytotoxicity was observed in spheroids. The microcarrier induced reductions in colony formation, alterations in cell cytoskeleton, and led to a significant reduction in P-glycoprotein expression compared to its free form, suggesting its potential to help to overcome drug resistance. These results point to the promising applicability of the hybrid microcarrier as an innovative delivery system for oral administration of cytotoxic agents.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125549"},"PeriodicalIF":5.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795474","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":"Unraveling local heat generation in twin-screw melt granulation","authors":"Niyati Niranjan Kodange ,&nbsp;Adwait Pradhan ,&nbsp;Fengyuan Yang ,&nbsp;Kapish Karan ,&nbsp;Quyen Schwing ,&nbsp;Thomas Durig ,&nbsp;Feng Zhang","doi":"10.1016/j.ijpharm.2025.125563","DOIUrl":"10.1016/j.ijpharm.2025.125563","url":null,"abstract":"<div><div>Granule growth in twin-screw melt granulation (TSMG) is driven by viscous and frictional heat dissipation at the kneading block. The formation of larger, stronger granules requires the screws to input more energy into processing the material, resulting in local heat generation (ΔT_local), as indicated by difference between the peak granule temperature and the set barrel temperature. Understanding ΔT_local is essential for comprehending TSMG and expanding its use in pharmaceutical manufacturing. This study examined the effects of process parameters and binder levels on ΔT_local using paracetamol or acetaminophen (APAP) as model drug and Klucel<!--> <!-->Fusion^TM X HPC (hydroxypropyl cellulose) as binder. The Q/N ratio (feed rate to screw speed), representing degree of fill, and the staggering angle of the kneading block significantly impacted ΔT_local. Specific mechanical energy (SME) showed a strong correlation with ΔT_local, with higher SME resulting in greater ΔT_local. These results highlighted the complex interaction between process parameters and binder levels, and their combined effect on SME and ΔT_local. Materials were exposed to elevated temperatures (93 °C to 110 °C) for short duration (≤33 s). Higher SME and ΔT_local led to increased particle size reduction of APAP post-granulation. Granule growth was achieved at a low binder level (5 % Klucel<!--> <!-->Fusion^TM X HPC), producing tablets with the desired tensile strength (&gt; 2 MPa) and less drug’s particle size reduction compared to a 10 % binder level. These findings underscore the benefits of using the 5 % binder in TSMG for effective granulation with minimal particle size reduction of the drug during granulation.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125563"},"PeriodicalIF":5.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787712","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":"Transdermal administration of macromolecular drugs by multi-frequency sequential ultrasonic irradiation","authors":"Kengo Matsubara ,&nbsp;Daichi Konosu ,&nbsp;Munenari Itoh ,&nbsp;Hirotaka J. Okano ,&nbsp;Kentaro Nakamura ,&nbsp;Yuta Kurashina","doi":"10.1016/j.ijpharm.2025.125560","DOIUrl":"10.1016/j.ijpharm.2025.125560","url":null,"abstract":"<div><div>Administration methods of macromolecular drugs with high efficacy and minimal side effects are generally limited to highly invasive injections due to their components and large molecular weight. Here, we propose a sequential ultrasonic irradiation method using multi-frequency for minimally invasive administration of macromolecular drugs. In this demonstration, low-frequency ultrasound (kHz band) and high-frequency ultrasound (MHz band) were sequentially irradiated onto the porcine skin to evaluate the dosing efficiency using fluorescence-modified ovalbumin (Mw = 45 kDa), a macromolecular drug model. Quantitative evaluation of the transdermal dosage by fluorescence intensity measurement shows that the proposed method significantly increased the transdermal dosage by almost double that of the conventional method. In particular, the distance of MHz ultrasonic irradiation is indicated to influence the dosing efficiency. In addition, the evaluation of transdermal permeability by confocal observation of skin sections shows that the macromolecular drug model penetrates through the epidermis of porcine skin, including the stratum corneum, to the dermis layer with the proposed method. The proposed method permeated the drug model with a behavior correlated to the intensity of the MHz ultrasonic beam, as opposed to the discrete penetration of the drug model in the conventional method. Our results provide a minimally invasive method of administering macromolecular drugs as an alternative to injection.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125560"},"PeriodicalIF":5.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787750","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}