Biological & pharmaceutical bulletin最新文献_第10页

Involvement of Cannabinoid Receptors and Adenosine A2B Receptor in Enhanced Migration of Lung Cancer A549 Cells Induced by γ-Ray Irradiation. 大麻素受体和腺苷A2B受体参与γ射线诱导的癌症A549细胞迁移增强。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 Epub Date: 2023-11-03 DOI: 10.1248/bpb.b23-00631

Misaki Oyama, Misaki Sakamoto, Kazuki Kitabatake, Kanami Shiina, Daisuke Kitahara, Sohei Onozawa, Keisuke Nishino, Yuka Sudo, Mitsutoshi Tsukimoto

{"title":"Involvement of Cannabinoid Receptors and Adenosine A2B Receptor in Enhanced Migration of Lung Cancer A549 Cells Induced by γ-Ray Irradiation.","authors":"Misaki Oyama, Misaki Sakamoto, Kazuki Kitabatake, Kanami Shiina, Daisuke Kitahara, Sohei Onozawa, Keisuke Nishino, Yuka Sudo, Mitsutoshi Tsukimoto","doi":"10.1248/bpb.b23-00631","DOIUrl":"10.1248/bpb.b23-00631","url":null,"abstract":"Residual cancer cells after radiation therapy may acquire malignant phenotypes such as enhanced motility and migration ability, and therefore it is important to identify targets for preventing radiation-induced malignancy in order to increase the effectiveness of radiotherapy. G-Protein-coupled receptors (GPCRs) such as adenosine A2B receptor and cannabinoid receptors (CB1, CB2, and GPR55) may be involved, as they are known to have roles in proliferation, invasion, migration and tumor growth. In this study, we investigated the involvement of A2B and cannabinoid receptors in γ-radiation-induced enhancement of cell migration and actin remodeling, as well as the involvement of cannabinoid receptors in cell migration enhancement via activation of A2B receptor in human lung cancer A549 cells. Antagonists or knockdown of A2B, CB1, CB2, or GPR55 receptor suppressed γ-radiation-induced cell migration and actin remodeling. Furthermore, BAY60-6583 (an A2B receptor-specific agonist) enhanced cell migration and actin remodeling in A549 cells, and this enhancement was suppressed by antagonists or knockdown of CB2 or GPR55, though not CB1 receptor. Our results indicate that A2B receptors and cannabinoid CB1, CB2, and GPR55 receptors all contribute to γ-radiation-induced acquisition of malignant phenotypes, and in particular that interactions of A2B receptor and cannabinoid CB2 and GPR55 receptors play a role in promoting cell migration and actin remodeling. A2B receptor-cannabinoid receptor pathways may be promising targets for blocking the appearance of malignant phenotypes during radiotherapy of lung cancer.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"60-71"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular Guanosine and Guanine Nucleotides Decrease Viability of Human Breast Cancer SKBR-3 Cells. 细胞外鸟苷和鸟嘌呤核苷酸降低人癌症SKBR-3细胞的活力。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 Epub Date: 2023-10-25 DOI: 10.1248/bpb.b23-00402

Ai Hotani, Kazuki Kitabatake, Mitsutoshi Tsukimoto

{"title":"Extracellular Guanosine and Guanine Nucleotides Decrease Viability of Human Breast Cancer SKBR-3 Cells.","authors":"Ai Hotani, Kazuki Kitabatake, Mitsutoshi Tsukimoto","doi":"10.1248/bpb.b23-00402","DOIUrl":"10.1248/bpb.b23-00402","url":null,"abstract":"Though the physiological effects of adenosine and adenine nucleotides on purinergic receptors in cancer cells have been well studied, the influence of extracellular guanosine and guanine nucleotides on breast cancer cells remains unclear. Here, we show that extracellular guanosine and guanine nucleotides decrease the viability and proliferation of human breast cancer SKBR-3 cells. Treatment with guanosine or guanine nucleotides increased mitochondrial production of reactive oxygen species (ROS), and modified the cell cycle. Guanosine-induced cell death was suppressed by treatment with adenosine or the equilibrium nucleoside transporter (ENT) 1/2 inhibitor dipyridamole, but was not affected by adenosine receptor agonists or antagonists. These results suggest that guanosine inhibits adenosine uptake through ENT1/2, but does not antagonize adenosine receptors. In contrast, guanosine triphosphate (GTP)-induced cell death was suppressed not only by adenosine and dipyridamole, but also by the A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), suggesting that GTP-induced cell death is mediated in part by an antagonistic effect on adenosine A1 receptor. Thus, both guanosine and GTP induce apoptosis of breast cancer cells, but via at least partially different mechanisms.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"14-22"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50160555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteomic Analysis of Staphylococcus aureus Treated with ShangKeHuangShui. 上克黄水治疗金黄色葡萄球菌的蛋白质组分析。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00471

Lichu Liu, Na Zhao, Kuangyang Yang, Honghong Liao, Xiaofang Liu, Ying Wu, Yan Wang, Xiao Peng, Yuanyan Wu

{"title":"Proteomic Analysis of Staphylococcus aureus Treated with ShangKeHuangShui.","authors":"Lichu Liu, Na Zhao, Kuangyang Yang, Honghong Liao, Xiaofang Liu, Ying Wu, Yan Wang, Xiao Peng, Yuanyan Wu","doi":"10.1248/bpb.b23-00471","DOIUrl":"10.1248/bpb.b23-00471","url":null,"abstract":"Staphylococcus aureus (SAU) stands as the prevailing pathogen in post-traumatic infections, with the emergence of antibiotic resistance presenting formidable treatment hurdles. The pressing need is to explore novel antibiotics to address this challenge. ShangKeHuangShui (SKHS), a patented traditional Chinese herbal formula, has gained widespread use in averting post-traumatic infections, but its biological effects remain incomplete understanding. This study's primary objective was to delve into the antibacterial properties, potential antibacterial compounds within SKHS, and their associated molecular targets. In vitro SKHS antibacterial assays demonstrated that the minimum inhibitory concentration (MIC) was 8.625 mg/mL and the minimum bactericide concentration (MBC) was 17.25 mg/mL. Proteomic analysis based on tandem mass tag (TMT) showed significant changes in the expression level of 246 proteins in SKHS treated group compared to control group, with 79 proteins upregulated and 167 proteins downregulated (>1.5-fold, p < 0.05). Subsequently, thirteen target proteins related to various biological processes and multiple metabolic pathways were selected to conduct parallel reaction monitoring (PRM) and molecular docking screen. In protein tyrosine phosphatase PtpA (ptpA) docking screening, phellodendrine and obacunone can bind to ptpA with the binding energy of - 8.4 and - 8.3 kcal/mol, respectively. This suggests their potential impact on antibacterial activity by modulating the two-component system of SAU. The discovery lays a groundwork for future research endeavors for exploring new antibacterial candidates and elucidating specific active chemical components within SKHS that match target proteins. Further investigations are imperative to unveil the biological effects of these monomers and their potential synergistic actions.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 1","pages":"292-302"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Mechanism of 5-Fluorouracil-Induced Hyperpigmentation in HRM-2 Hairless Mice: Focus on the Increase of Blood Vessels. 5-氟尿嘧啶诱导 HRM-2 无毛小鼠色素沉着过度的机制：关注血管的增加。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00584

Atsuo Fujito, Shota Tanaka, Keiichi Hiramoto, Ning Ma, Kazuya Ooi

{"title":"The Mechanism of 5-Fluorouracil-Induced Hyperpigmentation in HRM-2 Hairless Mice: Focus on the Increase of Blood Vessels.","authors":"Atsuo Fujito, Shota Tanaka, Keiichi Hiramoto, Ning Ma, Kazuya Ooi","doi":"10.1248/bpb.b23-00584","DOIUrl":"10.1248/bpb.b23-00584","url":null,"abstract":"5-Fluorouracil (5-FU), an effective chemotherapeutic agent for many solid tumors, has long been reported to cause pigmentation in patients treated intravenously, which occurs with increasing frequency of administration and decreases the QOL of the patients. Although melanin accumulation is thought to be the cause, the mechanism of pigmentation induced by 5-FU administration remains unclear, and there is no effective treatment for this problem. In this study, we investigated the mechanism of pigmentation induced by continuous 5-FU administration in 9-week-old male HRM-2 hairless mice for 8 weeks by focusing on the blood vessels for basic verification. In the auricular skin of 5-FU-administered mice, hyperpigmentation caused by melanin accumulation was observed macroscopically and by Fontana-Masson Staining. In addition, the expression of tyrosinase, melanin synthase, and blood vessel markers in the auricular skin was increased by 5-FU-administration in mice auricular skin. Other anticancer agents, cytarabine (Ara-C) and irinotecan (CPT-11), were also administered, and the differences between them and 5-FU were investigated; these changes were not observed in the auricles of these mice. These results suggest that tyrosinase is associated with 5-FU-induced melanin production and that an increase in blood vessels may be involved. Furthermore, pigmentation with melanin accumulation in the basal epidermal layer is a characteristic finding of 5-FU compared with Ara-C and CPT-11. In conclusion, this study indicates that 5-FU causes hyperpigmentation by melanin accumulation in a characteristic manner, including an increase in blood vessels.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 1","pages":"311-317"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Errata for Biological and Pharmaceutical Bulletin. 生物与制药公报》勘误表。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-e4702b

引用次数: 0

Reasons and Predictors of Treatment Change in Rheumatoid Arthritis Patients Treated with Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs: A Single-Center Retrospective Observational Study. 使用生物制剂和靶向合成改善病情抗风湿药物治疗的类风湿关节炎患者改变治疗方案的原因和预测因素：单中心回顾性观察研究》。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00366

Chihiro Nakagawa, Ryosuke Ota, Atsushi Hirata, Satoshi Yokoyama, Takaya Uno, Kouichi Hosomi

{"title":"Reasons and Predictors of Treatment Change in Rheumatoid Arthritis Patients Treated with Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs: A Single-Center Retrospective Observational Study.","authors":"Chihiro Nakagawa, Ryosuke Ota, Atsushi Hirata, Satoshi Yokoyama, Takaya Uno, Kouichi Hosomi","doi":"10.1248/bpb.b24-00366","DOIUrl":"10.1248/bpb.b24-00366","url":null,"abstract":"Rheumatoid arthritis (RA) patients receiving biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) often experience treatment changes due to inefficacy or adverse events. The purpose of this study was to clarify the incidence and reasons for change of b/tsDMARDs in a cohort of Japanese patients with RA and to identify the predictors of treatment change. This was a retrospective observational study of RA patients prescribed b/tsDMARD between April 2011 and December 2020 at the Kindai University Nara Hospital. We focused on the change of first-line b/tsDMARDs and identified the reasons for change using the electronic medical records. Logistic regression analysis was performed to identify predictors of treatment change as the objective variable and baseline characteristics as the explanatory variable. The reasons for treatment change were inefficacy in 69.6% of cases and adverse events in 29.7% of cases. Concomitant administration of higher dose prednisolone at baseline (adjusted odds ratio: [95% confidence interval]: 2.52 [1.19-5.33]) and old age (2.00 [1.03-3.87]) were associated with change in b/tsDMARD treatment due to inefficacy within 2 years of initiation. A better understanding of b/tsDMARDs persistence and elucidating the predictors of treatment change can help improve treatment outcomes for RA.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 10","pages":"1759-1767"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional Expression of Carnitine/Organic Cation Transporter 1 in Murine Choroid Plexus. 肉碱/有机阳离子转运体 1 在小鼠脉络丛中的功能表达

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00451

Takahiro Ishimoto, Noritaka Nakamichi, Takayuki Taguchi, Misa Nishiyama, Yukio Kato

{"title":"Functional Expression of Carnitine/Organic Cation Transporter 1 in Murine Choroid Plexus.","authors":"Takahiro Ishimoto, Noritaka Nakamichi, Takayuki Taguchi, Misa Nishiyama, Yukio Kato","doi":"10.1248/bpb.b24-00451","DOIUrl":"10.1248/bpb.b24-00451","url":null,"abstract":"Membrane transporters expressed in the choroid plexus (CP) are involved in the transport of substances between the blood and cerebrospinal fluid (CSF). Carnitine/organic cation transporter 1 (OCTN1, also known as SLC22A4) is expressed in rodent CP; however, its specific roles in blood-CSF transport remain unclear. Therefore, in this study, we aimed to evaluate the potential role of OCTN1 in the elimination of substances from CSF. Tritium-labeled ergothioneine ([3H]ERGO), a typical in vivo substrate of OCTN1, was injected into the lateral ventricles of wild-type and octn1 gene knockout (octn1-/-) mice. Clearance of [3H]ERGO from CSF was higher than that of the bulk flow marker, [14C]mannitol, in wild-type mice. However, [3H]ERGO clearance was significantly lower in octn1-/- mice than in wild-type mice. Furthermore, OCTN1 expression in CP was determined via immunohistochemical analysis. CP/CSF ratio of [3H]ERGO was significantly lower in octn1-/- mice than in wild-type mice. These results suggest that OCTN1 is functionally expressed in CP and involved in the elimination of ERGO from CSF in mice.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 9","pages":"1484-1486"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activation of Mitochondria in Mesenchymal Stem Cells by Mitochondrial Delivery of Coenzyme Q₁₀. 通过线粒体输送辅酶 Q10 激活间充质干细胞中的线粒体。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00284

Yuji Maruo, Masahiro Shiraishi, Mitsue Hibino, Jiro Abe, Atsuhito Takeda, Yuma Yamada

{"title":"Activation of Mitochondria in Mesenchymal Stem Cells by Mitochondrial Delivery of Coenzyme Q10.","authors":"Yuji Maruo, Masahiro Shiraishi, Mitsue Hibino, Jiro Abe, Atsuhito Takeda, Yuma Yamada","doi":"10.1248/bpb.b24-00284","DOIUrl":"https://doi.org/10.1248/bpb.b24-00284","url":null,"abstract":"The efficacy of mesenchymal stem cell (MSC) transplantation has been reported for various diseases. We previously developed a drug delivery system targeting mitochondria (MITO-Porter) by using a microfluidic device to encapsulate Coenzyme Q10 (CoQ10) on a large scale. The current study aimed to confirm if treatment with CoQ10 encapsulated by MITO-Porter enhanced mitochondrial functions in MSCs, with the potential to improve MSC transplantation therapy. We used highly purified human bone marrow-derived MSCs, described as rapidly expanding clones (RECs), and attempted to control and increase the amount of CoQ10 encapsulated in the MITO-Porter using microfluidic device system. We treated these RECs with CoQ10 encapsulated MITO-Porter, and evaluated its cellular uptake, co-localization with mitochondria, changes in mitochondrial respiratory capacity, and cellular toxicity. There was no significant change in mitochondrial respiratory capacity following treatment with the previous CoQ10 encapsulated MITO-Porter; however, mitochondrial respiratory capacity in RECs was significantly increased by treatment with CoQ10-rich MITO-Porter. Utilization of a microfluidic device enabled the amount of CoQ10 encapsulated in MITO-Porter to be controlled, and treatment with CoQ10-rich MITO-Porter successfully activated mitochondrial functions in MSCs. The MITO-Porter system thus provides a promising tool to improve MSC cell transplantation therapy.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 8","pages":"1415-1421"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Asperuloside Suppresses the Development of Depression through Wnt3α/GSK-3β Signal Pathway in Rats. 阿片苷通过Wnt3α/GSK-3β信号通路抑制大鼠抑郁症的发展

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00200

Li Yin, Chengshu Lu, Shiyuan Zeng, Deqi Jiang, Guofang Zeng, Huakun Wang

{"title":"Asperuloside Suppresses the Development of Depression through Wnt3α/GSK-3β Signal Pathway in Rats.","authors":"Li Yin, Chengshu Lu, Shiyuan Zeng, Deqi Jiang, Guofang Zeng, Huakun Wang","doi":"10.1248/bpb.b24-00200","DOIUrl":"10.1248/bpb.b24-00200","url":null,"abstract":"Depressive disorder is the most common mental disorder with significant economic burden and limited treatments. Traditional Chinese medicine monomer has emerged as a promising non-pharmacological treatment for reducing depressive symptoms. The aim of this study was to investigate the antidepressant-like effects of asperuloside (ASP) and its mechanism. The depression-like behaviors of chronic unpredictable mild stress (CUMS)-exposed rats were evaluated by behavioral tests. At the same time, the behaviors of rats treated with different concentrations of ASP (10, 20, 40 mg/kg) were also evaluated. RNA sequencing was performed to screen for dysregulated genes following ASP treatment. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to state the enriched pathways. Protein expression was detected by Western blotting. With the increase of ASP concentration (over 20 mg/kg), the depression-like behaviors of the rats were alleviated, which was manifested as the increase of the number of entries in the central zone, decrease of immobility time, and the increase of swimming time, sucrose preference, and body weight. ASP activated the Wnt3α/glycogen synthase kinase 3β (GSK-3β)/β-catenin signaling pathway in vivo. Knockdown of β-catenin reversed the effects of ASP on regulating depression-like behaviors. ASP alleviates depression-like behaviors by activating the Wnt3α/GSK-3β/β-catenin signaling pathway, indicating that ASP may be a potential therapeutic drug for treatment of depression.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 10","pages":"1637-1643"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessment of in Vivo Performance of Lipid-Based Formulations: Correlation between in Vitro Drug Release Profiles and in Vivo Absorption Rate Profiles. 评估脂质制剂的体内性能：体外药物释放曲线与体内吸收率曲线之间的相关性

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00458

Haruki Higashino, Takato Masada, Keiko Minami, Makoto Kataoka, Shinji Yamashita

{"title":"Assessment of in Vivo Performance of Lipid-Based Formulations: Correlation between in Vitro Drug Release Profiles and in Vivo Absorption Rate Profiles.","authors":"Haruki Higashino, Takato Masada, Keiko Minami, Makoto Kataoka, Shinji Yamashita","doi":"10.1248/bpb.b24-00458","DOIUrl":"https://doi.org/10.1248/bpb.b24-00458","url":null,"abstract":"The purpose of this study was to assess the in vivo absorption enhancement effects of lipid-based formulations (LBFs) through in vitro release studies. The type IIIA-MC (medium-chain) and type IIIA-LC (long-chain) formulations containing a Biopharmaceutics Classification System (BCS) Class II drug (dipyridamole or ketoconazole) were used as model LBFs. The type IIIA-MC formulation, but not the type IIIA-LC formulation, showed a higher initial absorption rate than the control suspension for both model drugs in rats. An in vitro side-by-side chamber system coupled with a lipid digestion model was used to measure free drugs, available for intestinal absorption, that are released from a model LBF. The profiles of free drug concentration on the donor side were determined by calculating the ratio of permeation rate (LBF/suspension) at every sampling interval. The in vitro free drug concentration was immediately supersaturated when the digestion of type IIIA-MC formulation was initiated for both drugs, which would cause the initially high absorption rate in rats. In contrast, the free concentration of the type IIIA-LC formulation became lower than the equilibrium solubility over time for both drugs. Overall, the profiles of in vitro free concentrations were consistent with those of in vivo absorption rates for both drugs and all LBFs. These findings would help predict the in vivo performance and establish an in vitro-in vivo correlation (IVIVC) of LBFs.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 10","pages":"1616-1623"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0