Frontiers in drug delivery最新文献

{"title":"Transnasal-brain delivery of nanomedicines for neurodegenerative diseases.","authors":"Xu Zhang, Maohua Wang, Zhixian Liu, Ying Wang, Li Chen, Jiaqi Guo, Wentao Zhang, Yao Zhang, Chenjie Yu, Tongwu Bie, Youjun Yu, Bing Guan","doi":"10.3389/fddev.2023.1247162","DOIUrl":"10.3389/fddev.2023.1247162","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) have become a serious global health problem as the population ages. Traditionally, treatment strategies for NDs have included oral and intravenous administration; however, the blood-brain barrier (BBB) can prevent drugs from reaching the brain, rendering the treatment incomplete and the effect unsatisfactory. Additionally, the prolonged or excessive use of drugs that can cross the BBB can damage liver and kidney function. Recent studies have shown that nose-to-brain drug delivery can noninvasively bypass the BBB, allowing drugs to enter the brain through the olfactory or trigeminal nerve pathways; additionally, nanoparticle carriers can enhance drug delivery. This review introduces drug carrier nanoparticles for nose-to-brain delivery systems, compares the advantages and disadvantages of different nanoparticles, and discusses the factors influencing nose-to-brain nanomedicine delivery and enhancement strategies. We also summarize nose-to-brain delivery and nanomedicines for treating NDs, the current challenges of this approach, and the future promise of nanomedicine-based ND treatment.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1247162"},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42743187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of simulated brain interstitial fluid flow on the chemokine CXCL12 release from an alginate-based hydrogel in a new 3D <i>in vitro</i> model.","authors":"Wiam El Kheir, Anaïs Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon","doi":"10.3389/fddev.2023.1227776","DOIUrl":"10.3389/fddev.2023.1227776","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Extensive investigation has been undertaken regarding drug delivery systems for the management of glioblastoma multiforme (GBM). The infiltrative behavior of GBM cells within the brain tissue is primarily attributed to their heterogeneity, the movement of interstitial fluid (IFF), and the presence of chemokines. These factors contribute to the limited effectiveness of current conventional treatments. To address the dissemination of GBM cells, a proposed therapeutic approach involves utilizing a controlled release gradient of CXC-chemokine-ligand-12 (CXCL12). However, the impact of IFF on GBM cell migration within the brain underscores its critical importance as a significant parameter, which, surprisingly, has not been extensively studied in the context of localized drug delivery targeting the brain. &lt;b&gt;Methods:&lt;/b&gt; Hydrogels are known for their inherent capacity to entrap various agents and exert precise control over their subsequent release. In the present investigation, we aimed to elucidate the release kinetics of CXCL12, whether in its free form or encapsulated within nanoparticles, from alginate-based hydrogels, both under static and dynamic conditions. To investigate the impact of convective forces mimicking the interstitial fluid flow (IFF) within the peritumoral environment of the brain, a three-dimensional &lt;i&gt;in vitro&lt;/i&gt; model was developed. This model enabled the evaluation of CXCL12 release as a function of time and position, specifically accounting for the contribution of simulated IFF on the release behavior. &lt;b&gt;Results:&lt;/b&gt; We first demonstrated that the release kinetic profiles under static culture conditions were independent of the initial mass loading and the predominant phenomenon occurring was diffusion. Subsequently, we investigated the release of CXCL12, which was loaded into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded within an alginate hydrogel matrix. Mathematical modeling results also indicated the presence of electrostatic interactions between alginate and CXCL12. The Alg/Chit-NPs effectively slowed down the initial burst release, leading to a reduction in the diffusion coefficient of CXCL12. To further study the release behavior, we developed a perfusion bioreactor with a unique culture chamber designed to recapitulate the peritumoral environment and varied the fluid flow rates at 0.5 µL/min, 3 µL/min, 6.5 µL/min, and 10 µL/min. As the flow rate increased, the cumulative amount of released CXCL12 also increased for all three initial mass loadings. Beyond 3 µL/min, convection became the dominant mechanism governing CXCL12 release, whereas below this threshold, diffusion played a more prominent role. &lt;b&gt;Conclusion:&lt;/b&gt; The indirect perfusion flow had a crucial impact on CXCL12 release and distribution inside the hydrogel in and against its direction. This system highlights the importance of considering the IFF in brain targeting delivery system and will be used in the future to","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1227776"},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46252690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyethylene Glycol-grafted poly alpha-lipoic acid-dexamethasone nanoparticles for osteoarthritis.","authors":"Yuanqiang Cheng, Zheng Jing, Yan Xu, Lihui Sun, Dongbo Li, Jianguo Liu, Dongsong Li","doi":"10.3389/fddev.2023.1168287","DOIUrl":"10.3389/fddev.2023.1168287","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a chronic inflammatory disease that causes synovial hyperplasia, cartilage destruction, and the formation of bone spurs. Macrophages play an indispensable role in the pathogenesis of OA by producing proinflammatory cytokines. To achieve the effect of arthritis, hormones can effectively inhibit the progression of inflammation by inhibiting the secretion of inflammatory cytokines by macrophages in traditional therapy. However, the drug is quickly cleared from the joint space, and the high injection site infection rate and low local drug concentration make the clinical efficacy of corticosteroids greatly reduced. We described the design and preparation of Polyethylene Glycol-grafted Poly Alpha-lipoic Acid-dexamethasone Nanoparticles (NP_DXM/PPLA), elucidated the mechanism of action of NP_DXM/PPLA in the treatment of OA in mice, and provided an experimental basis for investigating the treatment of OA with polymer nanoparticles loaded with dexamethasone. Flow cytometry and confocal laser scanning microscopy were used to confirm that NP_DXM/PPLA was well absorbed and released by macrophages, and it was discovered that NP_DXM/PPLA could efficiently reduce the proliferation of activated macrophages (RAW 264.7 cells). Enzyme-linked immunosorbent assay revealed that NP_DXM/PPLA could efficiently reduce the expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α. The knee bone structure of OA mice was investigated by MicroCT, and it was discovered that intraarticular injection of NP_DXM/PPLA effectively alleviated the bone damage of the articular cartilage. Therefore, NP_DXM/PPLA is a potential therapeutic nanomedicine for the treatment of OA.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1168287"},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47476855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Strategies to overcome the barriers to effective inhaled treatments.","authors":"Philip Chi Lip Kwok, Mohammad A M Momin, Basanth Babu Eedara, Shing Fung Chow","doi":"10.3389/fddev.2023.1253709","DOIUrl":"10.3389/fddev.2023.1253709","url":null,"abstract":"","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1253709"},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45235751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of large volume subcutaneous injections using computed tomography imaging and simultaneous pressure measurements.","authors":"Mona Purcell, Sahab Babaee, Michael Galluppi, John Cline, Guangli Hu, Ioan Petrescu, Jennifer Hughes, Meredith Allen, Eric Messina, Steven Persak, Yogita Krishnamachari, Ashley Lay-Fortenbery, Corin O Miller","doi":"10.3389/fddev.2023.1223177","DOIUrl":"10.3389/fddev.2023.1223177","url":null,"abstract":"<p><p>Many commercially available biologics, previously delivered only intravenously, are being re-formulated for subcutaneous delivery to improve patient access and compliance. However, due to inherent solubility limitations, large volume injections (more than 2 mL) are typically required. Different strategies are being explored to improve the tolerability of such injections, including the co-formulation with hyaluronidase and/or implementing different needle designs. While there have been separate reports of measuring injection forces and using imaging to track injection delivery and tissue response, there is no current set of methods to simultaneously characterize the injection delivery (bleb) and measure injection pressures. In this study we describe the development of Computed Tomography imaging methods in minipigs to characterize the morphology of the bleb following injection, along with inline pressure measurements to assess subcutaneous pressure during injection using two different injection volumes, 4.5 mL and 9 mL. We show that these parameters change with injection volume, and that inclusion of hyaluronidase in the injection increases bleb dispersion and reduces skin distention while also lowering the injection pressure. This method will likely be a valuable tool for assessing and comparing different injection delivery methods and formulations.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"1 1","pages":"1223177"},"PeriodicalIF":0.0,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69813363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AAV2 and AAV9 tropism and transgene expression in the mouse eye and major tissues after intravitreal and subretinal delivery.","authors":"Sanna Koponen, Emmi Kokki, Toni Tamminen, Seppo Ylä-Herttuala","doi":"10.3389/fddev.2023.1148795","DOIUrl":"10.3389/fddev.2023.1148795","url":null,"abstract":"<p><p><b>Introduction:</b> The eye is an excellent target for gene therapy because of its anatomical features. Gene therapy to treat ocular disorders relies on efficient gene delivery and transgene expression in the target cells. The aim of this study was to compare the biodistribution and safety of two different AAV serotypes after intravitreal (IVT) and subretinal injections. <b>Methods:</b> AAV2 (1 × 10¹² vg/mL) and AAV9 (5 × 10¹² vg/mL) vectors expressing an enhanced green fluorescent protein (EGFP) and an AAV9-empty (6 × 10¹¹ vg/mL) vector were injected intravitreally or subretinally into both eyes of adult C57Bl/OlaHsd mice. The biodistribution of the viral vectors in the eye and off-target tissues was studied using qPCR. GFP expression was studied from cryosections, and GFP transduction efficacy was verified using immunohistostaining for GFP. In addition, electroretinography (ERG) was used to assess the effect of vectors on retinal function. <b>Results:</b> In addition to the eyes, viral vector copies were found in distant off-target tissues such as the liver, especially after AAV9-EGFP IVT and subretinal injections. AAV9-EGFP injections showed more GFP expression throughout the retina compared to AAV2-EGFP. AAV2-EGFP IVT showed transgene expression mainly in the ganglion cell layer, whereas subretinal injection showed GFP expression in the retinal pigment epithelium. In addition, GFP was expressed at a moderate level in the liver after both injection routes of AAV9 and in parts of the brain after all injection groups except AAV9-empty. Lowered a- and b-amplitude values were seen in ERG in both scotopic and photopic experiments after AAV9-EGFP subretinal injection compared to all other groups. <b>Discussion:</b> This study shows that intraocular injection of AAV2 and AAV9 transduces retinal cells. Although the more efficient transduction of the retina, negative effect on the retinal function, and off-target transgene expression of AAV9 makes AAV2 a more suitable gene delivery vector to treat ocular disorders.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1148795"},"PeriodicalIF":0.0,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45602483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferrin receptor-targeting property of pabinafusp alfa facilitates its uptake by various types of human brain-derived cells <i>in vitro</i>.","authors":"Tomoki Fukatsu, Hanae Morio, Tomomi Furihata, Hiroyuki Sonoda","doi":"10.3389/fddev.2023.1082672","DOIUrl":"10.3389/fddev.2023.1082672","url":null,"abstract":"<p><p>Pabinafusp alfa, which is an anti-mucopolysaccharidosis II drug, consists of iduronate-2-sulfatase (IDS) genetically fused with an anti-transferrin receptor (TfR) antibody. While IDS is known to enter cells via mannose-6-phosphate receptor (M6PR)-mediated endocytosis, the anti-TfR antibody moiety of pabinafusp alfa is supposed to trigger the TfR-mediated transcytosis involved in its blood-brain barrier (BBB) penetration to deliver IDS into the brain, which thus makes it effective for treatment of brain symptoms of the disease. However, since these uptake processes remain unexamined <i>in vitro</i>, this study aims at elucidating how human brain cells manipulate these receptors to facilitate pabinafusp alfa uptake. The results of pabinafusp alfa uptake assays showed that the TfR played an primary role in its uptake by brain microvascular endothelial cells. The TfR contribution was also found in neuronal cells at levels comparable to M6PR. Interestingly, the predominant roles of TfR over M6PR in pabinafusp alfa uptake were also observed in astrocytes and pericytes. To summarize, our results support the TfR-targeting strategy of pabinafusp alfa for facilitating its BBB penetration while simultaneously identifying previously unnoticed TfR roles in its uptake into human neuronal and non-neuronal brain cells. These findings are certain to provide important insights into the mechanisms behind clinical actions of pabinafusp alfa.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1082672"},"PeriodicalIF":0.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44905517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of respirable sprayed microparticles of encapsulated bacteriophages.","authors":"Alberto Baldelli, Mingtao Liang","doi":"10.3389/fddev.2023.1209534","DOIUrl":"10.3389/fddev.2023.1209534","url":null,"abstract":"<p><p>Antibiotic resistance is exponentially increasing, and the number of deaths caused by bacterial infections is expected to surge. When dealing with the respiratory system, inefficient antibiotics heighten the chance of death from bacterial infection. However, the alternatives to antibiotics are limited. Bacteriophages are a valid option since they can target a specific type of bacterium. Bacteriophages are highly specific and can avoid any side effects when delivered. However, their poor stability makes their use inefficient. Encapsulation is commonly used to protect any bioactive compound for different types of delivery. In the case of respiratory delivery, particle engineering is used to generate stable dry powders to target the nasal or lung areas. This review article provides a guideline for engineering a process of nasal dry powders of encapsulated bacteriophages.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"3 1","pages":"1209534"},"PeriodicalIF":0.0,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41705974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On a model-based approach to improve intranasal spray targeting for respiratory viral infections.","authors":"Mohammad Mehedi Hasan Akash, Yueying Lao, Pallavi A Balivada, Phoebe Ato, Nogaye K Ka, Austin Mituniewicz, Zachary Silfen, Julie D Suman, Arijit Chakravarty, Diane Joseph-McCarthy, Saikat Basu","doi":"10.3389/fddev.2023.1164671","DOIUrl":"10.3389/fddev.2023.1164671","url":null,"abstract":"<p><p>The nasopharynx, at the back of the nose, constitutes the dominant initial viral infection trigger zone along the upper respiratory tract. However, as per the standard recommended usage protocol (\"Current Use\", or CU) for intranasal sprays, the nozzle should enter the nose almost vertically, resulting in sub-optimal nasopharyngeal drug deposition. Through the Large Eddy Simulation technique, this study has replicated airflow under standard breathing conditions with 15 and 30 L/min inhalation rates, passing through medical scan-based anatomically accurate human airway cavities. The small-scale airflow fluctuations were resolved through use of a sub-grid scale Kinetic Energy Transport Model. Intranasally sprayed droplet trajectories for different spray axis placement and orientation conditions were subsequently tracked via Lagrangian-based inert discrete phase simulations against the ambient inhaled airflow field. Finally, this study verified the computational projections for the upper airway drug deposition trends against representative physical experiments on sprayed delivery performed in a 3D-printed anatomic replica. The model-based exercise has revealed a new \"Improved Use\" (or, IU) spray usage protocol for viral infections. It entails pointing the spray bottle at a shallower angle (with an almost horizontal placement at the nostril), aiming slightly toward the cheeks. From the conically injected spray droplet simulations, we have summarily derived the following inferences: (a) droplets sized between 7-17 <i>μ</i>m are relatively more efficient at directly reaching the nasopharynx via inhaled transport; and (b) with realistic droplet size distributions, as found in current over-the-counter spray products, the targeted drug delivery through the IU protocol outperforms CU by a remarkable 2 orders-of-magnitude.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1164671"},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45625566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of transport systems involved in eflornithine delivery across the blood-brain barrier.","authors":"Christopher P Watson, Gayathri Nair Sekhar, Sarah A Thomas","doi":"10.3389/fddev.2023.1113493","DOIUrl":"10.3389/fddev.2023.1113493","url":null,"abstract":"<p><p>Human African Trypanosomiasis (HAT) is a neglected parasitic disease that continues to persist in sub-Saharan Africa. It is fatal if untreated. The first stage of the disease is associated with the presence of the parasite in the periphery and the second stage with the presence of the parasites in the CNS. The treatment of CNS stage HAT requires the drugs to cross the blood-brain barrier (BBB). Eflornithine is an amino acid analogue that is used to treat second stage HAT gambiense both alone and in combination with nifurtimox. Recent studies have identified that accumulation of eflornithine into the parasites (trypanosomes) involves the amino acid transporter (<i>Trypanosoma brucei</i> AAT6). In this study we tested the hypothesis that eflornithine uses a cationic amino acid transport system to cross the BBB. We particularly focused on system-y⁺ and system-B^0,+. To do this we utilized specialist databases to compare the physicochemical characteristics of relevant molecules and an <i>in vitro</i> model of the BBB to explore the mechanisms of eflornithine delivery into the CNS. Our results confirmed that eflornithine is related to the endogenous amino acid, ornithine. At pH 7.4, eflornithine is predominately (92.39%) a zwitterionic (dipolar) amino acid and ornithine is predominately (99.08%) a cationic (tripolar) amino acid. In addition, the gross charge distribution at pH 7.4 of eflornithine is much smaller (+0.073) than that of ornithine (+0.99). Further results indicated that eflornithine utilized a saturable transport mechanism(s) to cross the hCMEC/D3 cell membranes and that transport was inhibited by the presence of other amino acids including ornithine. Eflornithine transport was also sodium-independent and sensitive to a y⁺-system inhibitor, but not a B^0,+-system inhibitor. Eflornithine transport was also inhibited by pentamidine, suggestive of transport by organic cation transporters (OCT) which are expressed in this cell line. We confirmed expression of the y⁺-system protein, CAT1, and the B^0,+-system protein, ATB^0,+, in the hCMEC/D3 cells. We conclude that eflornithine uses the cationic amino acid transporter, system y⁺, and OCT to cross the BBB. This research highlights the potential of system-y⁺ to deliver drugs, including eflornithine, across the BBB to treat brain diseases.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1113493"},"PeriodicalIF":0.0,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42002808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}