Biopharmaceutics & Drug Disposition最新文献

{"title":"Development of a Biorelevant In Vitro Release System and Level A In Vitro-In Vivo Correlation for Doxorubicin Hydrochloride Liposome Injection via Flow-Through Cell Method","authors":"Xue-ting Huang,&nbsp;Jing-jing Liu,&nbsp;Xi-yang Tang,&nbsp;Guo Yin,&nbsp;Yi Dai,&nbsp;Xiao-wei Wang","doi":"10.1002/bdd.70036","DOIUrl":"10.1002/bdd.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>Doxorubicin hydrochloride liposome injection represents a complex nano-drug delivery system with significant clinical advantages, yet its quality evaluation remains challenging. Traditional static release methods often fail to simulate the physiological environment, which leads to poor in vivo predictions. The flow-through cell method provides distinct advantages by simulating hemodynamic characteristics and maintaining stable sink conditions. This study utilizes the flow-through cell method to simulate the release process of doxorubicin hydrochloride liposomes and establishes a Level A in vitro-in vivo correlation (IVIVC) based on the in vivo data of three commercial brands to develop a biorelevant in vitro release method. The in vivo cumulative release fraction is derived from the plasma concentration data of three commercial products using the fractional area (AUC) method for deconvolution, which serves as the target reference for the in vitro release profile. In vitro release experiments are conducted using a phosphate buffer containing 0.3% SDS and 15% artificial plasma as the release medium, which is optimized through single-factor analysis and an <i>L</i>₉ (3⁴) orthogonal experimental design. The experimental setup employs a dialysis membrane with a 300 KDa molecular weight cutoff and a flow rate of 4 mL/min. High-performance liquid chromatography (HPLC) determines the concentration of the released drug to calculate the in vitro cumulative release fraction. A Level A IVIVC model is established between the cumulative in vitro and in vivo release fractions of doxorubicin hydrochloride liposome injection, which is subsequently confirmed through internal validation. The IVIVC model demonstrates robust predictive capability, and the developed in vitro release method exhibits high sensitivity in distinguishing the release characteristics of products from different manufacturers. This study provides a scientific reference for the in vitro-in vivo correlation and quality evaluation of long-acting injections.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 3","pages":"138-149"},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954709","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}

{"title":"Prediction of Human Serum Concentration–Time Profiles of Golimumab and Ustekinumab Using Pharmacokinetic Data From Common Marmosets With Assessment of Anti-Drug Antibodies","authors":"Ayaka Tajiri,&nbsp;Shogo Matsumoto,&nbsp;Nanami Furukawa,&nbsp;Kensuke Kagiyama,&nbsp;Hiroshi Ikeda,&nbsp;Kazumasa Fukasawa,&nbsp;Hiroki Takano","doi":"10.1002/bdd.70035","DOIUrl":"10.1002/bdd.70035","url":null,"abstract":"<p>In a previous study, retrospective predictions of human serum concentration–time profiles for three therapeutic monoclonal antibodies (mAbs) with linear pharmacokinetics were performed using allometric scaling in common marmosets and achieved favorable predictability. To generalize this method, in the present study, golimumab and ustekinumab, which exhibit linear pharmacokinetics, were repeatedly administered to marmosets. Additionally, the immunogenicity of these mAbs in common marmosets was evaluated. Golimumab and ustekinumab were administered in four repeated doses. Following the initial administration, the scaling exponents of the two mAbs were calculated, and the average scaling exponents of the five mAbs were used for the predictions. Furthermore, serum anti-ustekinumab and anti-golimumab antibodies were evaluated following the repeated-dose administration. Human serum concentration–time curves of golimumab and ustekinumab were predicted using the average scaling exponents of the five mAbs. Although the predictability of the golimumab elimination rate was slightly inferior, ustekinumab showed excellent prediction performance. Low levels of anti-ustekinumab antibodies were detected in the serum when the serum ustekinumab levels were considered to have completely diminished. Furthermore, serum anti-golimumab antibodies were negligible during the experimental period. We identified provisional optimal scaling exponents for predicting human PK and found minimal anti-drug antibody formation. As the cost of acquiring and maintaining cynomolgus monkeys is increasing, pharmacokinetic data of marmosets is expected to encourage the potential use of these small non-human primates as an alternative model.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 3","pages":"127-137"},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdd.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized GFR Estimation Equations for Chinese Neonates and Children: Development of New Models and Comparison With Existing Ones","authors":"Hiotong Lam,&nbsp;Yahui Zhang,&nbsp;Zhe Hou,&nbsp;Jinfang Yuan,&nbsp;Zihan Lei,&nbsp;Haiyan Li,&nbsp;Xueting Yao,&nbsp;Tongyan Han,&nbsp;Dongyang Liu","doi":"10.1002/bdd.70032","DOIUrl":"10.1002/bdd.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>Glomerular filtration rate (GFR) maturation is critical for drug dosing in neonates and children. Current equations face dual limitations: they are primarily derived from Caucasian populations and fail to account for the fundamental physiological differences between neonates and children. This study aimed to develop Chinese-specific GFR equations and to characterize how the key predictors of GFR differ between these two developmental stages. Creatinine clearance as measured GFR (mGFR) in 58 hospitalized neonates (gestational age range, 30.3–41.0 weeks, postnatal age range, 0 to 26 days, mGFR = 3.08 ± 1.86 mL/min) without renal impairment were enrolled. Moreover, a published database of Chinese children (<i>N</i> = 87, age range, 1 to 18 years, mGFR = 97.0 ± 31.9 mL/min/1.73 m²) was applied. Demographic and renal function markers were included to develop equations using the stepwise regression method in allometric form. The GFR prediction equation of serum cystatin C, blood urea nitrogen and postmenstrual age of Chinese neonates was established. In children, GFR is associated with cystatin C, creatinine, weight and age. In an internal comparison with 16 published equations, our newly developed models showed favorable performance within our cohorts, with correlation (<i>R</i>² of 0.617 and 0.578) and accuracy (P₂₀ of 46.6% and 70.1%, P₅₀ of 93.1% and 100%), respectively. The equations would provide scientific basis for aiding diagnosis of renal function of Chinese neonates and children, and supporting better precision medicine of drugs mainly excreted by kidney.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 3","pages":"103-113"},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148271","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}

{"title":"Pharmacokinetic Assessment of Atazanavir and Favipiravir Following Echinacea Supplementation: A Controlled Herb–Drug Interaction Investigation","authors":"Siva Nageswara Rao Gajula,&nbsp;Jeevan Sai Kallam,&nbsp;Aarika Kanukolanu,&nbsp;Ganesh Korada,&nbsp;Lakshmi Vineela Nalla","doi":"10.1002/bdd.70034","DOIUrl":"10.1002/bdd.70034","url":null,"abstract":"<p><i>Echinacea</i> is a widely used herbal supplement and is frequently co-administered with antiviral drugs, raising concerns regarding potential herb–drug interactions. This study evaluated the effect of repeated <i>Echinacea</i> administration on the pharmacokinetics of favipiravir and atazanavir in rats. Male Sprague Dawley rats were administered <i>Echinacea</i> (250 mg/kg) or vehicle once daily for 10 days, followed by a single oral dose of favipiravir (70 mg/kg) or atazanavir (35 mg/kg). Plasma drug concentrations were quantified using validated LC–MS/MS methods, and pharmacokinetic parameters were determined by noncompartmental analysis. <i>Echinacea</i> co-administration did not significantly alter favipiravir exposure (<i>C</i>_max: 39,677 ± 5385 vs. 36,364 ± 5379 ng/mL; AUC0–t: 144,457 ± 17,267 vs. 104,840 ± 27,001 ng h/mL) or atazanavir exposure (<i>C</i>_max: 3274 ± 256 vs. 4004 ± 629 ng/mL; AUC0–t: 8962 ± 1667 vs. 10,645 ± 2949 ng h/mL). No relevant changes were observed in clearance, half-life, or mean residence time for either drug. These findings indicate that repeated <i>Echinacea</i> administration does not result in a pharmacokinetically relevant interaction with favipiravir or atazanavir under the investigated conditions.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 3","pages":"114-126"},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdd.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tebapivat: Pharmacokinetic Properties in Preclinical Species and Pharmacodynamic Responses Associated With Pyruvate Kinase Activation in Wild-Type Mice","authors":"Chuck Locuson,&nbsp;Sebastien Ronseaux,&nbsp;Michael McVay","doi":"10.1002/bdd.70037","DOIUrl":"10.1002/bdd.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>The investigation of pyruvate kinase activating drugs is expanding into previously untested diseases as the benefits of increasing glycolytic flux within pyruvate kinase-expressing tissues emerges. Recently, we reported the discovery of allosteric activator tebapivat, an investigational drug currently being studied in lower-risk myelodysplastic syndrome and sickle cell disease patients. This new compound is chemically distinct from the other marketed or investigational pyruvate kinase activators and demonstrated pharmacodynamic effects at low plasma exposures in healthy volunteers. To further distinguish the tebapivat chemotype, this report describes the pharmacokinetic and pharmacodynamic studies used to advance tebapivat to the clinic. Good oral bioavailability and low clearance were observed across animal species, but corrections for in vitro species differences in plasma binding were necessary to predict human clearance from animals. In mouse pharmacodynamic studies, blood biomarkers of pyruvate kinase activation reached near-maximum effect-area-under-the-curve changes at low oral dose (∼0.03 mg/kg). Lastly, we observed long-lived blood pharmacodynamics (up to 14 d), non-linear red blood cell partitioning, and the convergence of terminal blood drug concentrations from different doses in mice. We hypothesize these findings are most consistent with target-mediated drug disposition and are a result of the long residence time of tebapivat on its pharmacological target pyruvate kinase in red blood cells, and thus represents a subtle saturable property related to the high potency of tebapivat.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 3","pages":"150-159"},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987644","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}

{"title":"Ampicillin Is a Substrate of Organic Anion Transporters 3","authors":"Yu-Ting Liu,&nbsp;Xue-Yan Gou,&nbsp;Lu Gan,&nbsp;Yi-Mai MaLiu,&nbsp;Yan-Rong Ma,&nbsp;Xin-An Wu","doi":"10.1002/bdd.70024","DOIUrl":"10.1002/bdd.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>Ampicillin (AMP) is an organic anion drug widely used in clinical setting as a β-lactam antibiotic. However, the specific transporter involved in mediating AMP transport remains unidentified. Thus, we investigated whether organic anion transporters1/3 (OAT1/3) mediate the renal transport of AMP in this study. Both rOAT1/OAT3 (<i>Slc22a6/Slc22a8</i>) double-knockout and wild-type (WT) rats were administered AMP via intraperitoneal injection simultaneously. Following the knockout, a significant increase in AMP plasma concentration and the area under the plasma concentration–time curve (AUC) was observed, accompanied by a marked reduction in cumulative urinary excretion. OAT1/3-overexpressing cell uptake experiments demonstrated that AMP is a substrate of OAT3, with a Michaelis–Menten constant (<i>K</i>_<i>m</i>) of 138.6 μM and a maximum transport velocity (<i>V</i>_max) of 80.43 pmol/mg protein/min. In conclusion, AMP was identified as a substrate of OAT3, rather than OAT1.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 2","pages":"69-77"},"PeriodicalIF":2.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224814","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}

{"title":"Cyclooxygenase-2 Inhibition and Anti-Platelet Aggregation Activity of Astaxanthin-Hydrogel in Comparison to Celecoxib Against Rheumatoid Arthritis in Wistar Rat Model","authors":"Anzeela Ghaffar,&nbsp;Sumaira Sharif,&nbsp;Quindeel Naveed,&nbsp;Taimoor Aslam,&nbsp;Madeeha Shahzad Lodhi,&nbsp;Iffat Nayila","doi":"10.1002/bdd.70027","DOIUrl":"10.1002/bdd.70027","url":null,"abstract":"<div>\u0000 \u0000 <p>Rheumatoid arthritis is an auto-immune disease, commonly treated with celecoxib (Cyclooxygenase-2 inhibitor), which comes with serious cardiovascular threats. Astaxanthin is a natural carotenoid, possessing extraordinary anti-inflammatory and anti-platelet aggregation qualities. The aim of this study was to investigate the superlative effects of astaxanthin-hydrogel to inhibiting the cyclooxygenase-2 in comparison to celecoxib and its cardiac side-effects, specifically platelet aggregation. Induction of rheumatoid arthritis was accomplished by type-II-collagen/Complete Freund's adjuvant followed by a booster dose of Incomplete Freund's adjuvant and confirmed by arthritic score calculation, CRP and ACCPA tests. Astaxanthin-hydrogel was subcutaneously injected into the neck and back of arthritic Wistar rats in comparison to oral-celecoxib. Cyclooxygenase-2 inhibitory activity was observed by rat ELISA kit and platelet aggregation was monitored by optical chrono-log aggregometer. Results were compared by statistical analysis, executed through IBMM SPSS. The anti-inflammatory activity of 20 mg/week astaxanthin-hydrogel to inhibiting the cyclooxygenase-2 for 6 weeks in arthritic wistar rats was found more effective in comparison to 20 mg/day celecoxib. Continued use of 40 mg/day celecoxib for 8 weeks has been seen involved with platelet aggregation, whereas the regimen consisting of 20 mg/week astaxanthin-hydrogel administered with 20 mg/d celecoxib for 8 weeks was observed with no platelet aggregation. Celecoxib monotherapy was found associated with a little risk of platelet aggregation, whereas along with astaxanthin-hydrogel, no platelet aggregation was found. Notably, astaxanthin-hydrogel was significant to suppress the cyclooxygenase-2 in comparison to celecoxib.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 2","pages":"78-87"},"PeriodicalIF":2.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282209","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}

{"title":"Improvement of XZP8257 Dissolution Properties Through Amorphous and Mixed-Phase Precipitate Formation in Biorelevant Media","authors":"Miao Zhang,&nbsp;Shudong Zhang,&nbsp;Bin Wu,&nbsp;Zhe Zhang,&nbsp;Qin Hu,&nbsp;Lin Wang,&nbsp;Dongyang Liu","doi":"10.1002/bdd.70025","DOIUrl":"10.1002/bdd.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>Although precipitation of poorly soluble drugs in the gastrointestinal (GI) tract is often considered detrimental to bioavailability, the solid-state nature of the precipitate, either crystalline or amorphous, may critically redefine its impact. Contrasting with reported crystalline precipitates of weakly basic drugs, this study investigates XZP8257 (C₂₇H₂₃Cl₂N₃O₄S), a poorly soluble weakly acidic/zwitterionic compound (BCS II), to explore how GI fluid composition governs precipitate formation and its resulting physicochemical properties. Precipitates were generated in simulated intestinal media with varied bile salt concentrations and pH values. Their solid-state forms were characterized using XRD, SEM, FTIR, and DSC, whereas dissolution performance was evaluated via equilibrium solubility and intrinsic dissolution rate (IDR) measurements. Elevated bile salt concentrations induced a molecular structural transition in XZP8257 and facilitated the formation of crystalline–amorphous mixed precipitates, a phenomenon distinct from the crystalline precipitates typically reported. These novel precipitates exhibited a 5.29- to 22.1-fold increase in equilibrium solubility and a 0.7- to 2.35-fold improvement in IDR compared to the crystalline API. This study reveals that for weakly acidic compounds like XZP8257, precipitate formation in the GI tract can lead to high energy, readily redissolving solid forms, potentially enhancing rather than limiting absorption. This challenges the uniform negative view of precipitation and underscores the necessity of compound-specific precipitate characterization to accurately predict oral absorption, especially in physiologically based biopharmaceutics models.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 2","pages":"88-99"},"PeriodicalIF":2.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627145","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}

{"title":"A Slowly Self-Emulsifying Delivery System of Sesamin With Improved Biopharmaceutical Properties.","authors":"Duyen Thi My Ho, Kohei Yamada, Hideyuki Sato, Satomi Onoue","doi":"10.1002/bdd.70033","DOIUrl":"https://doi.org/10.1002/bdd.70033","url":null,"abstract":"<p><p>This study is the first attempt to develop a novel slowly self-emulsifying drug delivery system (SL-SEDDS) of sesamin (SES) for improved biopharmaceutical properties. Firstly, SES-loaded self-emulsifying drug delivery system (SEDDS/SES) comprising krill oil, medium-chain triglyceride, Tween 80, and propylene glycol with 1.5 w/w% SES loading was prepared and optimized using a pseudo-ternary phase diagram. Then, SES-loaded SL-SEDDS (SL-SEDDS/SES) was produced by mixing the optimized SEDDS/SES with varying Geleol (solid lipid) contents. The resulting formulations were evaluated in terms of their physicochemical properties and pharmacokinetics. The self-emulsifying potency of SL-SEDDS/SES remained largely unaffected by the presence of Geleol. The dissolution behavior of SES in SL-SEDDS/SES improved relative to that of crystalline SES, with sustained release that was dependent on Geleol content. Notably, SL-SEDDS/SES containing 20 w/w% Geleol content (SL-SEDDS/SES-20) performed favorable sustained release with 65% dissolved SES at 6 h. After oral administration of SES samples (20 mg-SES/kg) in rats, SL-SEDDS/SES-20 showed 7.9-fold higher area under the curve of plasma concentration-time profile than that of crystalline SES. Additionally, it reduced the peak systemic exposure observed with SEDDS/SES, with a 22% lower C_max and a prolonged mean residence time (MRT) of 5.3 h. These findings suggest that SL-SEDDS is a promising dosage form for enhancing the biopharmaceutical properties of SES and potentially other lipophilic nutraceuticals.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004306","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}

{"title":"Comparative Study on Cannabidiol-Loaded Solubilizing Systems for Improvement of Oral Bioavailability: Liposome and Cyclodextrin-Based Formulations","authors":"Hideyuki Sato,&nbsp;Kenta Watanabe,&nbsp;Ryuji Yagi,&nbsp;Akifumi Yagi,&nbsp;Shingo Rikimura,&nbsp;Yoshitaka Shimizu,&nbsp;Kohei Yamada,&nbsp;Satomi Onoue","doi":"10.1002/bdd.70019","DOIUrl":"10.1002/bdd.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to develop a CBD-loaded liposomal formulation (LIP/CBD) to improve its physicochemical properties and oral bioavailability (BA). LIP/CBD was prepared by the conventional solvent injection method. The physicochemical and pharmacokinetic properties of CBD were evaluated to clarify the possible improvement in the biopharmaceutical properties of CBD by the application of a liposomal system. For comparison, a cyclodextrin-based CBD formulation (CD/CBD) was prepared as a conventional solubilization system. Uniform spherical liposomes of LIP/CBD were observed by transmission electron microscopy, and the mean particle size was calculated to be approximately 120 nm with a polydispersity index of 0.13 and a zeta potential of −68 mV. The amount of CBD dissolved from crystalline CBD was very low under simulated intestinal pH condition (pH 6.8) due to its poor solubility and dispersibility. In contrast, LIP/CBD significantly enhanced the dissolution of CBD, as evidenced by 8-fold higher dissolution amount than that of crystalline CBD. Oral absorption of CBD from crystalline CBD was very poor owing to its low water solubility and severe first-pass metabolism. Orally administered LIP/CBD and CD/CBD exhibited significant improvements of oral absorption with 22- and 5.3-fold higher systemic exposure, respectively. The <i>T</i>_max of LIP/CBD was longer than that of CD/CBD, possibly due to the contribution of lymphatic absorption enhanced by lipidic components. The application of a liposomal system to CBD could be a viable option to enhance the physicochemical properties and oral BA of CBD.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 1","pages":"3-11"},"PeriodicalIF":2.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846312","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}