International Journal of Pharmaceutics: X最新文献

{"title":"Feed factor profile prediction model for two-component mixed powder in the twin-screw feeder","authors":"Yuki Kobayashi ,&nbsp;Sanghong Kim ,&nbsp;Takuya Nagato ,&nbsp;Takuya Oishi ,&nbsp;Manabu Kano","doi":"10.1016/j.ijpx.2024.100242","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100242","url":null,"abstract":"<div><p>In continuous pharmaceutical manufacturing processes, it is crucial to control the powder flow rate. The feeding process is characterized by the amount of powder delivered per screw rotation, referred to as the feed factor. This study aims to develop models for predicting the feed factor profiles (FFPs) of two-component mixed powders with various formulations, while most previous studies have focused on single-component powders. It further aims to identify the suitable model type and to determine the significance of material properties in enhancing prediction accuracy by using several FFP prediction models with different input variables. Four datasets from the experiment were generated with different ranges of the mass fraction of active pharmaceutical ingredients (API) and the powder weight in the hopper. The candidates for the model inputs are (a) the mass fraction of API, (b) process parameters, and (c) material properties. It is desirable to construct a high-performance prediction model without the material properties because their measurement is laborious. The results show that using (c) as input variables did not improve the prediction accuracy as much, thus there is no need to use them.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000148/pdfft?md5=e39edc07e8ce19bfa70a064e4c6ae931&pid=1-s2.0-S2590156724000148-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140346680","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":"The interplay of poorly soluble drugs in dissolution from amorphous solid dispersions","authors":"Marcel Kokott,&nbsp;Jörg Breitkreutz,&nbsp;Raphael Wiedey","doi":"10.1016/j.ijpx.2024.100243","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100243","url":null,"abstract":"<div><p>In recent years, the application of fixed dose combinations of antiretroviral drugs in HIV therapy has been established. Despite numerous therapeutic benefits, this approach poses several challenges for the formulation development especially when poorly soluble drugs are considered. Amorphous solid dispersions (ASD) thereby have gained considerable interest in the pharmaceutical field, however, mainly including binary systems containing only one drug and a polymer. The <em>co</em>-formulation of two amorphous drugs can be accompanied by an immense increase in the complexity of the system as exemplarily reported for ritonavir and lopinavir embedded in a composite polymer matrix of PVPVA. The present study aims to present a new formulation approach to overcome the well-documented interaction during dissolution. Two different polymers, PVPVA and HPMCAS were used to produce ASDs for both drugs individually via hot-melt extrusion. The embedding of lopinavir in the slower dissolving polymer HPMCAS, while using PVPVA for ritonavir was found to significantly improve the overall dissolution performance compared to the individual use of PVPVA as well as to the commercial product Kaletra®. In addition, the use of different grades of HPMCAS demonstrated the possibility to further modify the dissolution profile. For a preliminary biorelevant assessment, the selected formulations were tested in a biphasic dissolution setup.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259015672400015X/pdfft?md5=0aee7123035bce40c8fcfd17e816b6a3&pid=1-s2.0-S259015672400015X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343929","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":"Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia","authors":"Bjad K. Almutairy ,&nbsp;El-Sayed Khafagy ,&nbsp;Mohammed F. Aldawsari ,&nbsp;Abdullah Alshetaili ,&nbsp;Hadil Faris Alotaibi ,&nbsp;Amr Selim Abu Lila","doi":"10.1016/j.ijpx.2024.100240","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100240","url":null,"abstract":"<div><p>Bimatoprost (BIM) is a prostaglandin F2α analogs originally approved for the treatment of glaucoma and ocular hypertension. Recent studies have highlighted its potential to boost hair growth. The objective of this investigation is to challenge the potential of spanlastics (SLs) as a surfactant-based vesicular system for promoting the cutaneous delivery of BIM for the management of alopecia. BIM-loaded spanlastics (BIM-SLs), composed of Span as the main vesicle component and Tween as the edge activator, were fabricated by ethanol injection method. The formulated BIM-SLs were optimized by 2³ full factorial design. The optimized formula (F1) was characterized for entrapment efficiency, surface charge, vesicle size, and drug release after 12 h (Q_12h). The optimized formula (F1) exhibited high drug entrapment efficiency (83.1 ± 2.1%), appropriate zeta potential (−19.9 ± 2.1 mV), Q_12h of 71.3 ± 5.3%, and a vesicle size of 364.2 ± 15.8 nm, which favored their cutaneous accumulation. In addition, <em>ex-vivo</em> skin deposition studies revealed that entrapping BIM within spanlastic-based nanogel (BIM-SLG) augmented the dermal deposition of BIM, compared to naïve BIM gel. Furthermore, <em>in vivo</em> studies verified the efficacy of spanlastic vesicles to boost the cutaneous accumulation of BIM compared to naive BIM gel; the AUC_0-12h of BIM-SLG was 888.05 ± 72.31 μg/mL.h, which was twice as high as that of naïve BIM gel (AUC_0-12h 382.86 ± 41.12 μg/mL.h). Intriguingly, BIM-SLG outperforms both naïve BIM gel and commercial minoxidil formulations in stimulating hair regrowth in an androgenetic alopecia mouse model. Collectively, spanlastic vesicles might be a potential platform for promoting the dermal delivery of BIM in managing alopecia.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000124/pdfft?md5=31c97412f1f763f28d6a16d81b46b73d&pid=1-s2.0-S2590156724000124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140321255","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":"Halofuginone-guided nano-local therapy: Nano-thermosensitive hydrogels for postoperative metastatic canine mammary carcinoma with scar removal","authors":"Runan Zuo ,&nbsp;Lingqing Kong ,&nbsp;Wanjun Pang ,&nbsp;Shanxiang Jiang","doi":"10.1016/j.ijpx.2024.100241","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100241","url":null,"abstract":"<div><p>In female dogs, the highest morbidity and mortality rates cancer are the result of mammary adenocarcinoma, which presents with metastases in the lung. Other than early surgical removal, however, no special methods are available to treat mammary adenocarcinoma. Because human breast cancer and canine mammary carcinoma share clinical characteristics and heterogeneity, the canine model is a suitable spontaneous tumor model for breast cancer in humans. In this study, the physical swelling method was used to prepare halofuginone-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) polymer micelles nano-thermosensitive hydrogels (HTPM-gel). Furthermore, HTPM-gel was investigated via characterization, morphology, properties such as swelling experiment and <em>in vitro</em> release with reflecting its splendid nature. Moreover, HTPM-gel was further examined its capability to anti-proliferation, anti-migration, and anti-invasion. Ultimately, HTPM-gel was investigated for its <em>in vivo</em> anticancer activity in the post-operative metastatic and angiogenic canine mammary carcinoma. HTPM-gel presented spherical under transmission electron microscope (TEM) and represented grid structure under scanning electron microscope (SEM), with hydrodynamic diameter (HD) of 20.25 ± 2.5 nm and <em>zeta</em> potential (ZP) of 15.10 ± 1.82 mV. Additionally, HTPM-gel own excellent properties comprised of pH-dependent swelling behavior, sustained release behavior. To impede the migration, invasion, and proliferation of CMT-U27 cells, we tested the efficacy of HTPM-gel. Evaluation of <em>in vivo</em> anti-tumor efficacy demonstrates HTPM-gel exhibit a splendid anti-metastasis and anti-angiogenic ability, with exhibiting ideal biocompatibility. Notably, HTPM-gel also inhibited the scar formation in the healing process after surgery. In summary, HTPM-gel exhibited anti-metastasis and anti-angiogenic and scar repair features. According to the results of this study, HTPM-gel has encouraging clinical potential to treat tumors with multifunctional hydrogel.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000136/pdfft?md5=9b24978aa3117713504a565872d6dea9&pid=1-s2.0-S2590156724000136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327644","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-invasive caffeinated-nanovesicles as adipocytes-targeted therapy for cellulite and localized fats","authors":"Lobna M. Khalil ,&nbsp;Wessam M. El-Refaie ,&nbsp;Yosra S.R. Elnaggar ,&nbsp;Hamdy Abdelkader ,&nbsp;Adel Al Fatease ,&nbsp;Ossama Y. Abdallah","doi":"10.1016/j.ijpx.2024.100236","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100236","url":null,"abstract":"<div><p>Caffeine (CAF) is a non-selective adenosine A1 receptor antagonist which predominates in fat cells. When CAF binds to adenosine receptors, it increases cyclic adenosine monophosphate; inhibiting adipogenesis and inducing fat lipolysis. Resveratrol (RSV) is an antioxidant polyphenol possessing different anti-obesity mechanisms. Topical application of both hydrophilic CAF and lipophilic RSV is limited.</p><p>This study aimed to develop novel caffeinated-resveratrol bilosomes (CRB) and caffeine-bilosomes (CB) that could non-invasively target and deposit in fat cells. RSV bilosomes (RB) were prepared as a non-targeted system for comparison. CRB showed nanosize (364.1 nm ±6.5 nm) and high entrapment for both active compounds. Rats treated topically with CRB revealed a significant decrease (<em>P</em> = 0.039) in body weight. Histological analysis of the excised skin demonstrated a reduction in the subcutaneous fatty layer thickness and a decrease in the size of connective tissue-imbedded fat cells. Kidney histological examination of RB-treated rats showed subcapsular tubular epithelial cells with cytoplasmic vacuolation. This reflects a systemic effect of RSV from the non-targeted RB compared to CRB, which had a targeting effect on the adipose tissue. In conclusion, CAF in CRB significantly enhanced RSV deposition in adipose tissue and assisted its local-acting effect for managing obesity and cellulite.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000082/pdfft?md5=965207ea439ea05c29d9d734c2f11dba&pid=1-s2.0-S2590156724000082-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137908","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":"A network of regulatory innovations to improve FDA quality assessments of human drug applications","authors":"Russie Tran,&nbsp;Grace Fraser,&nbsp;Adam C. Fisher,&nbsp;Sau L. Lee,&nbsp;Ashley Boam,&nbsp;Stelios Tsinontides,&nbsp;Jennifer Maguire,&nbsp;Lawrence X. Yu,&nbsp;Susan Rosencrance,&nbsp;Steven Kozlowski,&nbsp;Don Henry","doi":"10.1016/j.ijpx.2024.100239","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100239","url":null,"abstract":"<div><p>A network of regulatory innovations brings a holistic approach to improving the submission, assessment, and lifecycle management of pharmaceutical quality information in the U.S. This dedicated effort in the FDA’s Center for Drug Evaluation and Research (CDER) aims to enhance the quality assessment of submissions for new drugs, generic drugs, and biological products including biosimilars. These regulatory innovations include developing or contributing: (i) the Knowledge-Aided Assessment and Structured Application (KASA), (ii) a new common technical document for quality (ICH M4Q(R2)), (iii) structured data on Pharmaceutical Quality/Chemistry, Manufacturing and Controls (PQ/CMC), (iv) Integrated Quality Assessment (IQA), (v) the Quality Surveillance Dashboard (QSD), and (vi) the Established Conditions tool from the ICH Q12 guideline. The innovations collectively drive CDER toward a more coordinated, effective, and efficient quality assessment. Improvements are made possible by structured regulatory submissions, a systems approach to quality risk management, and data-driven decisions based on science, risk, and effective knowledge management. The intended result is better availability of quality medicines for U.S. patients.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000112/pdfft?md5=e8c8fe5fc89a8ee9a2360ed20920c21a&pid=1-s2.0-S2590156724000112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140160102","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":"Evaluating a targeted Palbociclib-Trastuzumab loaded smart niosome platform for treating HER2 positive breast cancer cells","authors":"Shaghayegh Saharkhiz ,&nbsp;Negar Nasri ,&nbsp;Nazanin Naderi ,&nbsp;Ghasem Dini ,&nbsp;Saeid Shirzadi Ghalehshahi ,&nbsp;Fateme Firoozbakht","doi":"10.1016/j.ijpx.2024.100237","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100237","url":null,"abstract":"<div><p>In this study, we present a targeted and pH-sensitive niosomal (pHSN) formulation, incorporating quantum dot (QD)-labeled Trastuzumab (Trz) molecules for the specific delivery of Palbociclib (Pal) to cells overexpressing human epidermal growth factor receptor 2 (HER2). FTIR analyses confirmed the successful preparation of the pHSNs and their bioconjugation. The labeled Trz-conjugated Pal-pHSNs (Trz-Pal-pHSNs) exhibited a size of approximately 170 nm, displaying a spherical shape with a neutral surface charge of −1.2 mV. Pal encapsulation reached ∼86%, and the release pattern followed a two-phase pH-dependent mechanism. MTT assessments demonstrated enhanced apoptosis induction, particularly in HER2-positive cells, by Trz-Pal-pHSNs. Fluorescence imaging further validated the internalization of particles into cells. In conclusion, Trz-Pal-pHSNs emerge as a promising platform for personalized medicine in the treatment of HER2-positive breast cancer.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000094/pdfft?md5=72f0b03793377c22e7fd9492588d41d1&pid=1-s2.0-S2590156724000094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134297","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":"Rationalized landscape on protein-based cancer nanomedicine: Recent progress and challenges","authors":"Zhechen Fan ,&nbsp;Haroon Iqbal ,&nbsp;Jiang Ni ,&nbsp;Naveed Ullah Khan ,&nbsp;Shahla Irshad ,&nbsp;Anam Razzaq ,&nbsp;Mohammad Y. Alfaifi ,&nbsp;Serag Eldin I. Elbehairi ,&nbsp;Ali A. Shati ,&nbsp;Jianping Zhou ,&nbsp;Hao Cheng","doi":"10.1016/j.ijpx.2024.100238","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100238","url":null,"abstract":"<div><p>The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000100/pdfft?md5=2a1875e2e0561c02f64b4fb2ab03e865&pid=1-s2.0-S2590156724000100-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140122571","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":"Dual-responsive chondroitin sulfate self-assembling nanoparticles for combination therapy in metastatic cancer cells","authors":"Ensieh Poursani ,&nbsp;Giuseppe Cirillo ,&nbsp;Manuela Curcio ,&nbsp;Orazio Vittorio ,&nbsp;Michele De Luca ,&nbsp;Antonella Leggio ,&nbsp;Fiore Pasquale Nicoletta ,&nbsp;Francesca Iemma","doi":"10.1016/j.ijpx.2024.100235","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100235","url":null,"abstract":"<div><p>In this study, we developed self-assembling nanoparticles (LCPs) able to trigger the release of Chlorambucil (Chl) and Doxorubicin (DOX) to MDA-MB-231 cells by exploiting the enzyme and redox signals. The DOX loaded LCPs was prepared by the self-assembly of two chondroitin sulphate (CS) derivatives, obtained by the covalent conjugation of Lipoic Acid (LA) and Chlorambucil (Chl) to the CS backbone. After the physic-chemical characterization of the conjugates by FT-IR, ¹H NMR, and determination of the critical aggregation concentration, spherical nanoparticles with mean hydrodynamic diameter of 45 nm (P.D.I. 0.24) and <em>Z</em>-potential of - 44 mV were obtained by water addition/solvent evaporation method. In vitro experiments for the release of Chl and DOX were performed in healthy and cancer cells, using a cell culture media to maintain the physiological intracellular conditions (pH 7.4) (and concentration of esterase and GSH. The results allowed the selective release of the payloads to be detected: Chl release of 0 and 41% were obtained after 2 h incubation in normal and in cancer cells respectively, while values of 35 (in healthy cells) and 60% (in cancer cells) were recorded for DOX release after 96 h. Finally, viability studies proved the ability of the newly proposed nanosystem to enhance the cytotoxic activity of the two drugs against cancer cells.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000070/pdfft?md5=625bb0fe8f8d17a646ce9861a6328e0a&pid=1-s2.0-S2590156724000070-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051728","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":"Design and validation of a custom-made system to measure transepithelial electrical impedance in human corneas preserved in active storage machine","authors":"Marielle Mentek ,&nbsp;Benjamin Peyret ,&nbsp;Siwar Zouari ,&nbsp;Sébastien Urbaniak ,&nbsp;Jean-Marie Papillon ,&nbsp;Emmanuel Crouzet ,&nbsp;Chantal Perrache ,&nbsp;Sophie Hodin ,&nbsp;Xavier Delavenne ,&nbsp;Zhiguo He ,&nbsp;Philippe Gain ,&nbsp;Gilles Thuret","doi":"10.1016/j.ijpx.2024.100234","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100234","url":null,"abstract":"<div><p>Corneal epithelial barrier represents one of the major limitations to ocular drug delivery and can be explored non-invasively through the evaluation of its electrical properties. Human corneas stored in active storage machine (ASM) could represent an interesting physiological model to explore transcorneal drug penetration. We designed a new system adapted to human corneas preserved in ASM to explore corneal epithelial barrier function ex-vivo. A bipolar set-up including Ag/AgCl electrodes adaptors to fit the corneal ASM and a dedicated software was designed and tested on freshly excised porcine corneas (<em>n</em> = 59) and human corneas stored 14 days in ASM (<em>n</em> = 6). Porcine corneas presented significant and proportional decrease in corneal impedance in response to increasing-size epithelial ulcerations and acute exposure to benzalkonium chloride (BAC) 0.01 and 0.05%. Human corneas stored 14 days in ASM presented a significant increase in corneal impedance associated with the restoration of a multi-layer epithelium and an enhanced expression of tight junctions markers zonula occludens 1, claudin 1 and occludin. These results support the relevance of the developed approach to pursue the exploration and development of human corneas stored in ASM as a physiological pharmacological model.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000069/pdfft?md5=1415dea1eb2579fd72e98a2f249aba2c&pid=1-s2.0-S2590156724000069-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725760","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}