Journal of pharmaceutical sciences最新文献_第6页

Freezing-induced protein aggregation in a bispecific antibody: Characterization and mechanistic insights.

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-27 DOI: 10.1016/j.xphs.2025.103711

Xiaofeng Lu, Blanca Domingo-Yenes, Noah Cohen, Elissa Grzincic

{"title":"Freezing-induced protein aggregation in a bispecific antibody: Characterization and mechanistic insights.","authors":"Xiaofeng Lu, Blanca Domingo-Yenes, Noah Cohen, Elissa Grzincic","doi":"10.1016/j.xphs.2025.103711","DOIUrl":"10.1016/j.xphs.2025.103711","url":null,"abstract":"<p><p>Aggregation or formation of high molecular weight species (HMWS) was observed with a pharmaceutical bispecific antibody (BsAb) during freeze-thaw and storage at -20 °C, but not at -80 °C. Several freezing stresses that may drive the protein aggregation were evaluated, including temperature, freeze concentration, ice formation, cooling rate, and cold denaturation. Experiments designed to identify the main aggregation mechanism and the drivers revealed that protein dimerization is the main mechanism and protein interaction with ice is the main driver of the protein aggregation. Additionally, higher molecular mobility at -20 °C (compared to -80 °C) propagates the aggregation. Molecular structure modeling of the single-chain variable fragment (scFv) revealed the steric clashes between amino acid residues at the core of the interface between the variable heavy (VH) and variable light (VL) domains, could be an intrinsic driver of the protein aggregation. The study presents an interesting case of sequence-specific product quality liability for bispecifics and provides insights into strategies for prevention and mitigation of the liability.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103711"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Trans-resveratrol-loaded nanostructured lipid carrier formulations for pulmonary drug delivery using medical nebulizers.

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-27 DOI: 10.1016/j.xphs.2025.103713

Iftikhar Khan, Maria Sabu, Nozad Hussein, Huner Omer, Chahinez Houacine, Wasiq Khan, Abdelbary Elhissi, Sakib Yousaf

{"title":"Trans-resveratrol-loaded nanostructured lipid carrier formulations for pulmonary drug delivery using medical nebulizers.","authors":"Iftikhar Khan, Maria Sabu, Nozad Hussein, Huner Omer, Chahinez Houacine, Wasiq Khan, Abdelbary Elhissi, Sakib Yousaf","doi":"10.1016/j.xphs.2025.103713","DOIUrl":"10.1016/j.xphs.2025.103713","url":null,"abstract":"<p><p>Aerosolization is a non-invasive approach of delivering drugs for both localized and systemic effects, specifically pulmonary targeting. The aim of this study was to deliver trans-resveratrol (TR) as an anti-cancer drug entrapped in a new generation versatile carriers nanostructured lipid carrier (NLC) to protect degradation and improve bioavailability via medical nebulizers. Twelve TR-NLC (i.e., F1-F12) formulations were prepared using different combinations and ratios of formulation ingredients via hot high-pressure homogenization. Upon analysis, formulations F1 and F2 demonstrated a particle size of <185 nm, a polydispersity index (PDI) <0.25, Zeta potential values of ∼30 mV and an entrapment efficiency >94%. The aerosolization performance of the F1 and F2 formulations was performed via a next generation impactor (NGI), using medical nebulizers. The air jet nebulizer demonstrated lower drug deposition in the earlier stages (1-2) and significantly higher deposition in the latter stages 3-5 (for both formulations), targeting middle to lower lung deposition. Moreover, the air jet nebulizer exhibited significantly higher emitted dose (ED) (87.44 ± 3.36%), fine particle dose (FPD) (1652.52 ± 9.68 µg) fine particle fraction (FPF) (36.25 ± 4.26%), and respirable fraction (RF) (93.41 ± 4.03%) when the F1 formulation was used as compared to the F2 formulation. Thus, the TR-NLC F1 formulation and air jet nebulizer were identified as the best combination for the delivery and targeting peripheral lungs.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103713"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Impact of Dry Ice Exposure on pH Change During Biologics Transport and Mitigation Strategies. 干冰暴露对生物制品运输过程中 pH 值变化的影响及缓解策略。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-27 DOI: 10.1016/j.xphs.2025.103709

Yu Wang, Dihan Su, Yu Yang, Xinyu Huang, Zhaowei Jin, Quanmin Chen, Hongbing Wu, Jeremy Guo

{"title":"The Impact of Dry Ice Exposure on pH Change During Biologics Transport and Mitigation Strategies.","authors":"Yu Wang, Dihan Su, Yu Yang, Xinyu Huang, Zhaowei Jin, Quanmin Chen, Hongbing Wu, Jeremy Guo","doi":"10.1016/j.xphs.2025.103709","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103709","url":null,"abstract":"<p><p>Cold chain with dry ice is extensively used in the pharmaceutical transportation. Containers designed for cryo-storage are often placed contact with CO<sub>2</sub> released from dry ice, yet the effects of CO<sub>2</sub> on drug formulations during pharmaceutical transportation are infrequently discussed. In this study, the impact of pH change on various containers and buffer systems, the ingress pathway of CO<sub>2</sub> and the mitigation control strategies were investigated. The findings revealed notable pH changes in various types of containers with 5 mL polycarbonate bottles, 150 mL Corning bottles, and plastic tubes, while glass vials with stopper and capping maintained better pH stability. Buffer systems with a higher initial pH, such as phosphate and Tris buffers, were more prone to disturbances. Additionally, buffers with higher ionic strength showed an enhanced capacity to counteract pH reductions. The probability of CO<sub>2</sub> ingress pathway largely depends on the integrity of the sealing approaches at low temperature. Control strategy involving temporary uncapping during thawing and the use of secondary packaging sealed with an aluminum foil bag during transportation proved effective. This research expounded the impact of dry ice on pH change and strategic control measures within pharmaceutical supply chains, aiming to improve understanding of the variables related to container use in scenarios involving dry ice transportation.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103709"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A target affinity enrichment workflow to characterize critical post-translational modifications within therapeutic antibodies 表征治疗性抗体中关键翻译后修饰的目标亲和力富集工作流程。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-27 DOI: 10.1016/j.xphs.2025.103710

Jethro E. Prinston , Wenjing Peng , Kathleen Provoncha , Youmi Moon , Evan Koufos , Cristinel Sandu , Yue Fu , Yuetian Yan , Shunhai Wang , Ning Li , Jennifer B. Nguyen , Michael P. Rosconi , Erica A. Pyles

{"title":"A target affinity enrichment workflow to characterize critical post-translational modifications within therapeutic antibodies","authors":"Jethro E. Prinston , Wenjing Peng , Kathleen Provoncha , Youmi Moon , Evan Koufos , Cristinel Sandu , Yue Fu , Yuetian Yan , Shunhai Wang , Ning Li , Jennifer B. Nguyen , Michael P. Rosconi , Erica A. Pyles","doi":"10.1016/j.xphs.2025.103710","DOIUrl":"10.1016/j.xphs.2025.103710","url":null,"abstract":"<div><div>The therapeutic efficacy of a monoclonal antibody (mAb) relies on tight and specific binding to its intended target. This interaction may be abrogated or influenced by antibody fragmentation and/or post-translational modifications (PTMs) on or near the paratope. PTMs with reduced target affinity are considered impactful to drug quality and should be well-characterized during pharmaceutical development. The task of identifying and characterizing these PTMs can be facilitated by employing a strategy which utilizes semi-preparative affinity chromatography using an immobilized ligand target. Here, we present a proof-of-concept application of this strategy for a therapeutic antibody targeting a Type I cytokine receptor. Briefly, a sub-molar equivalent of the therapeutic antibody was applied to a column containing the immobilized receptor target. Fractions containing antibody variants with differential affinity to target were collected and evaluated by a panel of extended characterization assays, including size, charge, target-binding affinity, and cell-based potency. This approach specifically targets variants based on ligand affinity and enabled the identification of novel and specific PTMs, including Fab glycosylation, which were shown to be impactful to drug quality and could be considered critical quality attributes (CQAs). Furthermore, characterization of affinity-enriched fractions using assays that are orthogonal and complimentary to those used for release could guide or support the development of such assays which are sufficiently sensitive to detect these PTMs during product release.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103710"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Strategies of Formulation and Lyophilization Process for Sodium Chloride-Mannitol-Protein-Based Products.

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-26 DOI: 10.1016/j.xphs.2025.01.007

Chenying Lin, Xiaozhang Zhang, Chunsheng Yang, Zhaowei Jin, Jeremy Guo

{"title":"Strategies of Formulation and Lyophilization Process for Sodium Chloride-Mannitol-Protein-Based Products.","authors":"Chenying Lin, Xiaozhang Zhang, Chunsheng Yang, Zhaowei Jin, Jeremy Guo","doi":"10.1016/j.xphs.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.01.007","url":null,"abstract":"<p><p>Sodium chloride (NaCl) serves as a necessary stabilizer for some proteins, yet it presents an unfriendly eutectic melting temperature and can easily lead to collapse for lyophilized products. Mannitol, serving as bulking agent with property of high eutectic melting point, can provide good mechanical support for lyophilized cake to avoid collapse, therefore it is applied for lyophilized formulations containing NaCl. However, the combination of NaCl and mannitol in formulations often results in structural collapse in lyophilization process due to unproper ratio or lyophilization recipe. In this study, the strategy to improve cake appearance with formulations containing NaCl and mannitol has been explored. The suitable lyophilization formulation compositions and lyophilization process parameters have been proposed with acceptable protein stability. Furthermore, the possibility of mutual inhibition by NaCl and mannitol crystallization is revealed by result of XRD, in which various mannitol crystal forms are observed. It is speculated that protein concentration and lyophilization process parameters are main factors to affect mannitol crystal forms. Our studies not only provide insights into the crystallization behaviors in NaCl-mannitol-protein-based formulations, but also find the strategies to improve the appearance of their lyophilized biopharmaceuticals, facilitating their widespread applications in pharmaceutical development.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Insights into interactions between taxanes and P-glycoprotein using biophysical and in silico methods 使用生物物理和硅学方法深入了解紫杉类药物与 P 糖蛋白之间的相互作用。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-25 DOI: 10.1016/j.xphs.2025.103708

Longwen Xu , Katherine G. Schaefer , Gavin M. King , Zhong-Ru Xie , Michael G. Bartlett

{"title":"Insights into interactions between taxanes and P-glycoprotein using biophysical and in silico methods","authors":"Longwen Xu , Katherine G. Schaefer , Gavin M. King , Zhong-Ru Xie , Michael G. Bartlett","doi":"10.1016/j.xphs.2025.103708","DOIUrl":"10.1016/j.xphs.2025.103708","url":null,"abstract":"<div><div>Multidrug resistance mediated by P-glycoprotein (Pgp) is a significant obstacle to cancer chemotherapy. Taxane drugs, including paclitaxel, docetaxel, and cabazitaxel, are used to treat multiple types of cancer. All taxane drugs are Pgp substrates, but cabazitaxel is also a Pgp inhibitor, indicating potential differential interactions between Pgp and different taxanes. Here, we showed for the first time that cabazitaxel had a partial inhibitory effect on the ATPase activity at concentrations higher than 10 µM. We found the <em>K<sub>D</sub></em> of paclitaxel, docetaxel, and cabazitaxel to Pgp are 0.85 µM, 40.59 µM, and 13.53 µM, respectively. Based on acrylamide quenching, paclitaxel induced Pgp into a wide inward-facing open conformation at a high concentration but a slightly occluded conformation at lower concentrations. Both docetaxel and cabazitaxel shifted Pgp towards occluded states, each drug resulting in a unique degree of occlusion. Furthermore, molecular docking and energy calculations revealed that cabazitaxel binds with the “access tunnel” and blocks the subsequent nucleotide-binding domain dimerization. Our results indicate that the preference of taxanes for different binding sites on Pgp leads to distinct transport mechanisms. These results provide valuable insight into the interaction between taxanes and Pgp, which will enhance future drug development.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103708"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Pediatric off-label use and nonadherence management for nadolol: A mechanistic PBPK model incorporating ontogeny scaling from interracial adults to children.

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-24 DOI: 10.1016/j.xphs.2025.103707

Xiang Chen, Guo Yu, Guangji Wang, Guo-Fu Li

{"title":"Pediatric off-label use and nonadherence management for nadolol: A mechanistic PBPK model incorporating ontogeny scaling from interracial adults to children.","authors":"Xiang Chen, Guo Yu, Guangji Wang, Guo-Fu Li","doi":"10.1016/j.xphs.2025.103707","DOIUrl":"10.1016/j.xphs.2025.103707","url":null,"abstract":"<p><p>Nadolol has demonstrated its superior efficacy over other β-blockers in the treatment of specific cardiovascular diseases in children. The clinical development of nadolol for pediatric use was prioritized by Chinese healthcare authorities in May 2023 while there was a lack of clear medication instructions for children. To expedite the pediatric development of nadolol and provide insights into its off-label applications, we developed a physiologically based pharmacokinetic model incorporating mechanistic disposition knowledge. This model integrates key processes of nadolol including P-glycoprotein (P-gp) transporter mediated the absorption of efflux, multidrug and toxin extrusion protein (MATE) 1 transporter and organic cation (OCT) 2 transporter mediated active renal excretion, organic anion transporting polypeptide (OATP) 1A2 mediated transport, along with biliary excretion. The model accurately captured the pharmacokinetic profiles of nadolol in both Western and East Asian populations following a wide dose range (2-160 mg), including the plasma concentration, urine excretion, and drug-drug interactions with the P-gp inhibitor. After our good validation on interracial adult populations, simulations of nadolol pharmacokinetic profiles in the Chinese population were performed by adjusting the liver volume of the Chinese to 0.9 of the Japanese population. Then, with the consideration of physiological changes and plasma protein ontogeny in pediatrics, the nadolol model for pediatrics was also well-verified on several children aged 3 months to 121 months. Accordingly, specific optimal dosages for children across various ages and racial backgrounds with or without obesity were offered by exposure matching with adults. Multiple remedial regimen simulations were also compared to obtain the best nonadherence management in the case of missed dosages, in which resuming a regular dose as soon as possible was the most recommended.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103707"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A novel method for encapsulating nutritional supplements within edible films

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-24 DOI: 10.1016/j.xphs.2025.103706

Gregory Smutzer, Omar Elamin

{"title":"A novel method for encapsulating nutritional supplements within edible films","authors":"Gregory Smutzer, Omar Elamin","doi":"10.1016/j.xphs.2025.103706","DOIUrl":"10.1016/j.xphs.2025.103706","url":null,"abstract":"<div><div>Many nutritional supplements are hydrophobic solids or oils that are extremely difficult to administer in tablet form. These supplements are often consumed as large soft gels that may represent a choking hazard. In addition, many nutritional supplements produce an aversive taste or tactile response when consumed orally. Because of these limitations, improved delivery methods for administering nutritional supplements to the oral cavity represent an important goal. In this study, vitamin E acetate is exploited as a model nutritional supplement for developing an improved oral delivery method by encapsulating this vitamin within rapidly dissolving edible films. Vitamin E acetate was solidified by mixing this oil with a long-chain fatty alcohol. The resulting wax was then pulverized and added to an aqueous polymer solution that included melted gelatin. The mixture was then sonicated to form a stable emulsion that was dried to a thin, flexible film. Vitamin E acetate was successfully encapsulated within films at amounts that approximated the minimum daily requirement for this supplement. Minimal loss of this vitamin occurred when the emulsion was dried to a film. Average film thickness was 150 µm, and the encapsulated vitamin E was not degraded. Film formulations that included the excipients sucralose and peppermint oil produced taste intensity ratings in the moderate range, and displayed favorable hedonic responses. In summary, rapidly dissolving edible films have been developed that greatly increase the load capacity of a hydrophobic oral supplement. These edible films represent a promising approach for delivering hydrophobic oils or solids to the oral cavity at bioavailable amounts.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 4","pages":"Article 103706"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Efflux and uptake of androgen sulfates using transporter-overexpressing HEK293 cells and membrane vesicles.

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-22 DOI: 10.1016/j.xphs.2025.103705

Arttu Uoti, Erkka Järvinen, Noora Sjöstedt, Jan Koenderink, Moshe Finel, Heidi Kidron

{"title":"Efflux and uptake of androgen sulfates using transporter-overexpressing HEK293 cells and membrane vesicles.","authors":"Arttu Uoti, Erkka Järvinen, Noora Sjöstedt, Jan Koenderink, Moshe Finel, Heidi Kidron","doi":"10.1016/j.xphs.2025.103705","DOIUrl":"10.1016/j.xphs.2025.103705","url":null,"abstract":"<p><p>Hydrophilic steroid conjugates require active and facilitated transport mechanisms for their distribution into tissues and excretion from the body. The ATP-binding cassette (ABC) and solute carrier organic anion (SLCO) transporters involved in androgen sulfate (-S) disposition have been poorly characterized. In this study, we investigated the in vitro transport of testosterone-S, epitestosterone-S, dehydroepiandrosterone-S (DHEA-S), androsterone-S, and etiocholanolone-S by the multidrug resistance-associated proteins 2-4 (MRP2-4, ABCC2-4), breast cancer resistance protein (BCRP, ABCG2), and organic anion-transporting polypeptides (OATP) 1B1, 1B3, and 2B1 (SLCO1B1, SLCO1B3, and SLCO2B1) using human transporter-overexpressing HEK293 cells and membrane vesicles. We found testosterone-S, epitestosterone-S, and DHEA-S to be selectively transported by BCRP and/or MRP4, whereas all studied androgen sulfates were substrates of MRP3, OATP1B1, OATP1B3, and OATP2B1. MRP2 did not transport any of the studied compounds. Evaluation of transport kinetics revealed MRP4 to interact with its substrates at high to moderate affinity, whereas the observed affinities towards MRP3, BCRP, and OATPs were mostly moderate. These results help to build a better mechanistic understanding of the disposition of androgen sulfates in the human body. Additionally, this data may be used to assess the feasibility of androgen sulfates as additional biomarkers in doping detection.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103705"},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Preparation, in vitro and in vivo evaluation and anti-renal injury effects of Niazimicin-loaded mixed polymeric micelles

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-02-22 DOI: 10.1016/j.xphs.2025.103703

Xia Jiang , Mingie Gong , Yue Jia , Michael Adu-Frimpong , Xiaowen Wang , Qinyang Hua , Tingyuan Li , Jiaying Li , Pengfei Pan , Elmurat Toreniyazov , Jiangnan Yu , Xia Cao , Qilong Wang , Ximing Xu

{"title":"Preparation, in vitro and in vivo evaluation and anti-renal injury effects of Niazimicin-loaded mixed polymeric micelles","authors":"Xia Jiang , Mingie Gong , Yue Jia , Michael Adu-Frimpong , Xiaowen Wang , Qinyang Hua , Tingyuan Li , Jiaying Li , Pengfei Pan , Elmurat Toreniyazov , Jiangnan Yu , Xia Cao , Qilong Wang , Ximing Xu","doi":"10.1016/j.xphs.2025.103703","DOIUrl":"10.1016/j.xphs.2025.103703","url":null,"abstract":"<div><h3>Background</h3><div>Chronic Kidney Disease (CKD) has become one of the major life-threatening conditions. Moringa seeds have been reported to exhibit renoprotective effects, with Niazimicin as its characteristic component. Objective: To investigate the anti-renal injury effects of Niazimicin and its mixed micelles (N-M) that composed of monomethyl ether poly (ethylene glycol)-polycaprolactone (mPEG-PCL) and polyethylene glycolated chitosan (PEG-CS) on adenine-induced CKD mice. Methods: PEG-CS was prepared via formaldehyde linkage method. The thin film dispersion method was employed for the preparation of N-M before it was characterized <em>in vivo</em> and <em>in vitro</em>. The anti-renal injury effects were evaluated by analyzing the serum levels of creatinine (Cr), p-Cresol sulphate (pCs), indole sulphate (IS) and hematoxylin-eosin (HE)-stained sections of hepatic and renal pathological tissues in CKD mice. Results: The N-M were spherical micelles of uniform size and highly dispersed with particle size of 42.94 ± 0.58 nm, encapsulation efficiency (EE) of 97.73 ± 2.33% and drug loading (DL) of 16.17 ± 0.28%, as well as good stability, and a very low critical micelle concentration (CMC) value of 0.00731 mg/mL. The N-M had a delayed-release effect and higher oral bioavailability compared to Niazimicin. Conclusion: In CKD mice, Niazimicin exhibited an anti-renal injury effect, while the renoprotective effect of N-M was superior to that of Niazimicin.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 4","pages":"Article 103703"},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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