International Journal of Pharmaceutics: X最新文献

{"title":"Comparing the transfection efficiency of cationic monomer ratios in vinylimidazole and aminoethyl methacrylate copolymers","authors":"Sahel Soghrati ,&nbsp;Jaleh Varshosaz ,&nbsp;Mahboubeh Rostami ,&nbsp;Mina Mirian ,&nbsp;Fariborz Sharifianjazi ,&nbsp;Ketevan Ta-vamaishvili","doi":"10.1016/j.ijpx.2025.100327","DOIUrl":"10.1016/j.ijpx.2025.100327","url":null,"abstract":"<div><div>Employing polycations as non-viral gene delivery vectors has been extensively studied owing to their safety, efficiency and possibility of modifying them in an intended way compared with viral vectors. However, the main challenge is finding a biocompatible and transfection-efficient polymer. In this study, 2-aminoethyl methacrylate (A) and 1-vinyl imidazole (V) were copolymerized at three different molar ratios by a free radical polymerization method and novel biocompatible polycations with narrow molecular weight distribution were obtained. The resulting copolymers were used for condensation of plasmid DNA (pDNA) at different N/P ratios followed by physicochemical characterizations of resulting polyplexes. At N/P ratio of 2, the nanoplexes were smaller than 120 nm. The optimum formulations were stable in presence of polyanions and capable of protecting the condensed pDNA against nucleases. The polyplexes having V to A molar ratio of 1:1 were the most efficient carrier in transfecting HeLa cells and were introduced as a promising non-viral vector.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100327"},"PeriodicalIF":5.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reticuloendothelial system blockade does not enhance siRNA-LNP circulation or tumor accumulation in mice","authors":"Pol Escudé Martinez de Castilla ,&nbsp;Mariona Estapé Senti ,&nbsp;Sigrun Erkens ,&nbsp;Wytske M. van Weerden ,&nbsp;Sander A.A. Kooijmans ,&nbsp;Marcel H. Fens ,&nbsp;Pieter Vader ,&nbsp;Raymond M. Schiffelers","doi":"10.1016/j.ijpx.2025.100324","DOIUrl":"10.1016/j.ijpx.2025.100324","url":null,"abstract":"<div><div>One of the biggest challenges for siRNA-based therapeutics is intracellular delivery into the target cell, which can be facilitated by encapsulating siRNA in lipid nanoparticles (LNPs). In this study, we formulated D-Lin-MC3-DMA-LNPs encapsulating siRNA against the androgen receptor (AR), a key driver in prostate cancer. We effectively knocked down AR expression at both the mRNA as well as protein levels <em>in vitro</em> in AR-expressing prostate cancer cell lines. However, when moving to <em>in vivo</em> studies, siRNA-LNP efficacy is hindered by rapid clearance by the reticuloendothelial system (RES) in the liver and spleen. We evaluated whether transient RES blockade through systemic pre-administration of dextran sulfate or liposomes could extend the circulation time and enhance tumor accumulation of siRNA-LNPs in tumor-bearing mice. In two different mouse prostate cancer (PCa) xenograft models, we observed that, upon systemic administration, LNPs still predominantly accumulated in the liver and spleen, with only limited tumor uptake. Our findings demonstrate that pre-treatment with dextran sulfate or liposomes did not enhance siRNA-LNP blood circulation time or tumor accumulation <em>in vivo</em>, indicating the need for alternative strategies to enhance siRNA-LNP delivery to tumors.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100324"},"PeriodicalIF":5.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fucoidan/Polyvinylpyrrolidone/Hesperitin nanoparticle complex for corneal injury treatment: Synthesis, characterization, and therapeutic efficacy","authors":"Yalu Liu ,&nbsp;Zhengpei Zhang ,&nbsp;Lina Guan ,&nbsp;Jie Li ,&nbsp;Xing Ge ,&nbsp;Xiaochen Wu ,&nbsp;Haiyang Liu","doi":"10.1016/j.ijpx.2025.100325","DOIUrl":"10.1016/j.ijpx.2025.100325","url":null,"abstract":"<div><div>Corneal injury is a common ailment that, if not addressed promptly and efficiently, has the potential to result in significant visual impairment. This study investigates the therapeutic potential of a novel FU/PVP/Hes nanoparticle complex composed of fucoidan (FU), polyvinylpyrrolidone (PVP), and hesperitin (Hes) for corneal injury treatment. The FU/PVP/Hes nanoparticles were synthesized using a solvent evaporation method and characterized for their morphology, size distribution, biocompatibility, antioxidant activity, and anti-inflammatory capacity. The nanoparticles demonstrated excellent biocompatibility with low hemolysis rates and minimal cytotoxicity. They also exhibited potent antioxidant and anti-inflammatory properties, which were attributed to the enhanced solubility and bioavailability of Hes through nanoparticle formation. <em>In vivo</em> investigations employing a mouse model of corneal injury induced by alkali burns showed that the FU/PVP/Hes nanoparticles significantly promoted corneal epithelial healing, reduced corneal opacity, and suppressed the elevation of inflammatory cytokines. Histopathological analysis confirmed the nanoparticles' ability to facilitate corneal tissue repair. The study concludes that the FU/PVP/Hes nanoparticle complex is a promising therapeutic agent for corneal injury treatment due to its biocompatibility and multifaceted therapeutic effects.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100325"},"PeriodicalIF":5.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RGD peptide-functionalized micelles loaded with crocetin ameliorate doxorubicin-induced cardiotoxicity","authors":"Ting Wang ,&nbsp;Zhimin Li ,&nbsp;Jiawei Lei ,&nbsp;Yuchen Zhang ,&nbsp;Yingpeng Tong ,&nbsp;Xingang Guan ,&nbsp;Shuangshuang Wang","doi":"10.1016/j.ijpx.2025.100326","DOIUrl":"10.1016/j.ijpx.2025.100326","url":null,"abstract":"<div><div>Doxorubicin (Dox)-induced cardiotoxicity presents a significant challenge to fully harnessing its chemotherapeutic potential. Crocetin (Cro), a dicarboxylic acid found in the crocus flower and gardenia fruit, has shown remarkable antioxidant and anti-inflammatory activities. However, its poor aqueous solubility and limited cellular uptake severely constrain its further application in treating diseases. In this study, we developed Arg-Gly-Asp (RGD) peptide-decorated nanomicelles delivering Cro to alleviate Dox-induced cardiac injury. The RGD@M(Cro) nanomicelles exhibited excellent aqueous solubility and a drug-loading efficiency of 93.3 %. RGD-decorated micelles could enhance the cellular uptake of Cro in cardiomyocytes and inhibit approximately 60 % of HL-1 cell apoptosis through efficient reactive oxygen species (ROS) scavenging. In a cardiomyopathy mouse model, RGD@M(Cro) substantially reduced cardiac damage and improved cardiac indicators. This study highlights the great potential of RGD-decorated micelles in treating cardiac injury and other diseases.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100326"},"PeriodicalIF":5.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral colon-targeted delivery of recombinant human MANF for alleviation of ulcerative colitis","authors":"Jie Zhou ,&nbsp;Tian-Le Li ,&nbsp;Bo Wei ,&nbsp;Yue-Feng Ruan ,&nbsp;Ye-Qin Wang ,&nbsp;Jiao-Yan Liu ,&nbsp;Meng-Meng Song ,&nbsp;Yu-Xian Shen","doi":"10.1016/j.ijpx.2025.100320","DOIUrl":"10.1016/j.ijpx.2025.100320","url":null,"abstract":"<div><div>Midbrain astrocyte-derived neurotrophic factor (MANF) is a secreted protein induced by endoplasmic reticulum stress. Previous studies have indicated that intravenous administration of 1 mg/kg/day recombinant human MANF protein with His tag (His-MANF) for 3 days can ameliorate acute ulcerative colitis in mice. However, long-term intravenous therapy has many disadvantages. In this paper, His-MANF protein was successfully encapsulated into alginate and hyaluronic acid hybrid hydrogel microcapsules in one step using the gas shear method and then coated by Eudragit S100 to construct an oral colon-targeted delivery system (MSH@E). The MSH@E microcapsules exhibited controlled and sustained release behavior and colon-targeting properties. Both fluorescent imaging and immunohistochemistry staining results showed that His-MANF protein could accumulate in the colitis colon for a longer residence time after oral delivery. In vivo studies demonstrated that oral administration of MSH@E microcapsules could alleviate DSS-induced colitis in mice without systemic toxicity. Importantly, even if the oral His-MANF dose was half of the intravenous His-MANF dose, oral delivery was still much more effective than intravenous injection, suggesting the development of the oral colon-targeted delivery system (MSH@E) has great significance and makes a breakthrough from intravenous to oral administration for His-MANF treatment of ulcerative colitis (UC).</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100320"},"PeriodicalIF":5.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin and EGCG combined formulation in nanostructured lipid carriers for anti-aging applications","authors":"Chidchanok Prathumwon ,&nbsp;Songyot Anuchapreeda ,&nbsp;Kanokwan Kiattisin ,&nbsp;Pawaret Panyajai ,&nbsp;Panikchar Wichayapreechar ,&nbsp;Young-Joon Surh ,&nbsp;Chadarat Ampasavate","doi":"10.1016/j.ijpx.2025.100323","DOIUrl":"10.1016/j.ijpx.2025.100323","url":null,"abstract":"<div><div>Curcumin (Cur) and epigallocatechin gallate (EGCG), the primary active compounds in turmeric and green tea, respectively, have been investigated for their anti-aging potential. The Cur and EGCG combination was encapsulated in sustained-release nanostructured lipid carriers (NLCs) to enhance their bioactivities and pharmaceutical properties. A significant enhancement in the antioxidant activities of the Cur and EGCG combination was observed at an optimal ratio, as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (118.83 ± 3.78 %), ferric ion reducing antioxidant power assay (217.25 ± 13.45 %), and lipid peroxidation inhibition assay (106.08 ± 12.93 %), compared to Cur alone without compromising the antioxidant activities and total phenolic content of EGCG. This is due to the enhancement of total phenolic content of the combination of 218.83 ± 10.57 %. For anti-aging activities, the combination exhibited stimulation of SIRT1 protein and inhibition of collagenase and elastase of 27.53 ± 0.73 %, 43.70 ± 1.05 % and 51.76 ± 6.52 % compared with that achieved with Cur alone, respectively. The incorporation of the Cur and EGCG combination into NLCs resulted in high entrapment efficiencies of 98.60 ± 0.05 % for Cur and 98.40 ± 0.08 % for EGCG, with corresponding loading capacities of 0.789 ± 0.001 % and 3.935 ± 0.003 %, respectively. When formulated NLCs into an emulgel base, the system demonstrated sustained release profiles over 48 h, with 12.82 ± 0.99 % release of Cur and 63.77 ± 5.76 % release of EGCG. Significant skin retention was also observed after 24 h, with 23.88 ± 1.71 % Cur and 22.79 ± 4.65 % EGCG retained in the skin. Therefore, Cur: EGCG-loaded NLCs in emulgel can deliver the active compounds into the dermis, enhancing skin penetration, sustained delivery, and anti-aging activity superior to each conventional single active compound in topical formulations.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100323"},"PeriodicalIF":5.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the potential of antifungal-loaded proniosomes to consolidate corneal permeation in fungal keratitis: A comprehensive investigation from laboratory characterization to microbiological evaluation","authors":"Sadek Ahmed ,&nbsp;Michael M. Farag ,&nbsp;Heba Attia ,&nbsp;Bander Balkhi ,&nbsp;Islam M. Adel ,&nbsp;Asmaa Ashraf Nemr","doi":"10.1016/j.ijpx.2025.100322","DOIUrl":"10.1016/j.ijpx.2025.100322","url":null,"abstract":"<div><div>This work aimed to prepare Terconazole loaded proniosomes (TCZ-PNS) utilizing modified coacervation technique for the management of fungal keratitis. Terconazole (TCZ) is a potent antifungal with poor aqueous solubility posing intricacies in its incorporation in ocular formulations. A 2³ factorial design was adopted to probe independent formulation variables including A: Lecithin: cholesterol ratio, B: Surfactant: cholesterol ratio and C: Span® 80 contribution (% of total SAA). The formulae, generated by the design, were prepared and scrutinized regarding entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). Numerical desirability algorithms selected an optimum TCZ-PNS which boasted plausible %EE (89.51 % ± 0.94 %), nanoscale vesicles consistent with TEM measurements (247.9 ± 0.42 nm), a sufficiently high ZP (−43.42 ± 0.85 mV), and an in-vitro biphasic release profile that remained stable even after Gamma irradiation and short-term storage. The transcorneal ex-vivo permeation of TCZ-PNS was higher than that of TCZ suspension (≈ 2-fold). The formulation was further evaluated for pH, corneal hydration threshold, and histopathological safety, confirming its suitability for ocular application. Confocal laser microscopy revealed substantial corneal uptake (approximately twice as deep as of TCZ suspension). Additionally, microbiological assessments of the optimal TCZ-PNS compared to TCZ suspension demonstrated an inhibition zone nearly 50 % larger, a significantly lower MIC and MFC (64-fold reduction), and enhanced biofilm inhibition activity across most tested concentrations. These findings suggest that TCZ-PNS could be a propitious treatment choice to deeply deliver antifungal therapy for the eradication of deeply rooted and inaccessible fungal keratitis.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100322"},"PeriodicalIF":5.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-destructive quantification of low colchicine concentrations in commercially available tablets using transmission raman spectroscopy with partial least squares","authors":"Ningzi Guo ,&nbsp;Sijing Niu ,&nbsp;Ying Geng ,&nbsp;Guangzhi Shan ,&nbsp;Ningyi Wei ,&nbsp;Hua Chen","doi":"10.1016/j.ijpx.2025.100321","DOIUrl":"10.1016/j.ijpx.2025.100321","url":null,"abstract":"<div><div>The narrow therapeutic index and significant toxicity of colchicine (COL) underscore the importance of content uniformity of dosage units to ensure drug safety and efficacy. In this study, transmission Raman spectroscopy (TRS) technology combined with partial least squares (PLS) regression was used for the non-destructive determination of low concentration levels of COL in commercial tablets (0.83 % <em>w</em>/w). Based on a multifactor orthogonal design of experiment, one hundred calibration tablets ranging in drug content from 70 % to 130 % of the label claim were manufactured to develop an initial model which was further calibrated using the HPLC results. The quantitative model displayed good repeatability and high accuracy with a root-mean-standard error for calibration of 0.038 % and root-mean-standard error for cross-validation of 0.039 %. The limits of detection and quantification were 0.13 % and 0.40 % <em>w</em>/w, respectively. The absolute value of relative error of the TRS and HPLC content results for commercial tablets varied between 0 and 3.8 %. Notably, the relative standard deviation (RSD) of the TRS method was 1.2 %, lower than the RSD of 2.9 % observed with HPLC. The results demonstrated a fast and non-destructive method for the quality control of highly toxic and low content active pharmaceutical ingredients in commercial products, without human or environmental exposure to toxic substances during sample preparation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100321"},"PeriodicalIF":5.2,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils-mediated accelerated blood clearance phenomenon in beagles and rats based on the cross-injection of non-PEGylated and PEGylated nanoemulsions","authors":"Mengyang Liu ,&nbsp;Jia Wang ,&nbsp;Ge Chen ,&nbsp;Lirong Wang ,&nbsp;Xuling Wang ,&nbsp;Bai Xiang ,&nbsp;Yihui Deng ,&nbsp;Chaoxing He ,&nbsp;Lei Wang","doi":"10.1016/j.ijpx.2025.100318","DOIUrl":"10.1016/j.ijpx.2025.100318","url":null,"abstract":"<div><div>The initial injection of PEGylated nanoparticles can activate antibodies and the complement system, leading to the accelerated blood clearance (ABC) phenomenon, characterized by reduced circulation time and abnormal liver and spleen accumulation upon re-exposure. However, PEGylation is not essential for ABC induction, as non-PEGylated nanoparticles can also trigger the similar ABC phenomenon. In this study, we found non-PEGylated nanoemulsions (CE) could accelerate the blood clearance of subsequent injection of PEGylated nanoemulsions (PE) in beagles and rats, which was independent of antibodies and the complement system, but was associated with an increase in neutrophil numbers and phagocytic activity. We propose classifying this as a “general ABC phenomenon,” broadening clinical relevance and highlighting potential immune risks of ABC phenomenon. The intensity of the ABC phenomenon correlated with the initial CE phospholipid dose in both species. Notably, larger CE particles (∼ 300 nm) induced the ABC phenomenon in beagles, while smaller particles (∼ 80 nm) with higher immunogenicity were required in rats. This suggested that beagles are more susceptible to CE-induced ABC phenomenon. The higher neutrophil proportion in beagles likely contributed to species differences in ABC phenomenon. This is the first study to report neutrophil involvement in ABC induction by non-PEGylated nanoparticles, more importantly, underscoring potential immune risks in the cross-injection of non-PEGylated and PEGylated nanoparticles during the developments and clinical applications of nano-drug delivery systems.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100318"},"PeriodicalIF":5.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced transdermal delivery of pioglitazone hydrochloride via conductive hydrogel microneedles combined with iontophoresis","authors":"Jianling Hu ,&nbsp;Yue An ,&nbsp;Weiqing Wang ,&nbsp;Jing Yang ,&nbsp;Wenxin Niu ,&nbsp;Xiumei Jiang ,&nbsp;Kun Li ,&nbsp;Changzhao Jiang ,&nbsp;Jincui Ye","doi":"10.1016/j.ijpx.2025.100317","DOIUrl":"10.1016/j.ijpx.2025.100317","url":null,"abstract":"<div><div>The conventional oral administration of pioglitazone for Type II diabetes management is frequently compromised by hepatic first-pass metabolism and associated systemic adverse effects, necessitating the development of enhanced transdermal delivery approaches. This study developed a transdermal drug delivery system combining conductive hydrogel microneedles and iontophoresis to improve the transdermal delivery of pioglitazone hydrochloride (PIO) and its therapeutic efficacy in the treatment of type II diabetes. The microneedles, fabricated using poly(methyl vinyl ether-<em>alt</em>-maleic anhydride) as the main matrix material, exhibited excellent conductivity, mechanical strength, and high drug loading capacity. In vitro permeation experiments demonstrated that, when combined with iontophoresis at a current intensity of 0.5 mA, the cumulative permeation of PIO reached 238.1 ± 27.14 μg/cm² within 48 h, significantly higher than that of the microneedle group alone. In a type II diabetic rat model, the microneedle-iontophoresis system displayed a significantly better hypoglycemic effect than the oral administration group, with a blood glucose reduction of 6.3 mmol/L on day 8, significantly higher than the 5.1 mmol/L reduction in the positive control group. Pharmacokinetic analysis indicated that the T_max, T_1/2, and mean residence time of the system were longer than those of oral administration, indicating sustained-release characteristics. Skin irritation tests revealed that the system caused only mild, transient skin irritation, with complete skin recovery within 24 h. In conclusion, conductive hydrogel microneedles combined with iontophoresis can effectively enhance PIO transdermal delivery, bioavailability, and therapeutic efficacy while also exhibiting good safety and potential clinical application value.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100317"},"PeriodicalIF":5.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}