Tamer Mohamed Mahmoud, Mohammed Ayad Alboreadi, Amr Gamal Fouad, Nada H Mohammed, Amany Belal, Fahad H Baali, Nisreen Khalid Aref Albezrah, Mohammed S Alharthi, Sherif Faysal Abdelfattah Khalil, Fatma I Abo El-Ela
{"title":"提高卡维地洛控制糖尿病相关性心力衰竭的疗效和生物利用度:体外和体内表征","authors":"Tamer Mohamed Mahmoud, Mohammed Ayad Alboreadi, Amr Gamal Fouad, Nada H Mohammed, Amany Belal, Fahad H Baali, Nisreen Khalid Aref Albezrah, Mohammed S Alharthi, Sherif Faysal Abdelfattah Khalil, Fatma I Abo El-Ela","doi":"10.1080/1061186X.2025.2573051","DOIUrl":null,"url":null,"abstract":"<p><p>Carvedilol (CRD) is an oral beta-adrenergic antagonist approved for treating heart failure (HF). However, due to its short half-life and poor solubility, CRD has limited bioavailability and effectiveness. This study aimed to develop a nasal spray of CRD-novasomes (CLN) to enhance CRD's sustainability, targeting, bioavailability, and efficacy as a therapy for diabetes mellitus-associated HF (DMHF). Several CLN formulations were created using Box-Behnken design and characterized in vitro to identify the optimized formulation, which was later evaluated in vivo using an experimental DMHF rat model. The selected optimized CLN formulation consists of 30.079 mg of oleic acid, 56.897 mg of Span 60, and 60 mg of cholesterol. The optimized CLN demonstrated significant improvements over free CRD, enhancing CRD's sustainability and permeability by 71.39% and 6.08-fold, respectively. When compared to oral free CRD, the nasal CLN increased the bioavailability and target efficiency of CRD by 5.74-fold and 4.24-fold, respectively. In relation to DMHF positive control, the nasal CLN significantly lowered glucose, LDH, and CK-MB levels by 93.68%, 94.29%, and 96.50%, respectively, showcasing its efficacy. Histopathological and toxicity studies further validated the activity and safety of the optimized CLN. These findings indicate that the nasal CLN spray shows potential as a therapy for DMHF.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-42"},"PeriodicalIF":3.9000,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Improving the Therapeutic Efficacy and Bioavailability of Carvedilol for Control of Diabetes-Associated Heart Failure: In Vitro and In Vivo Characterization.\",\"authors\":\"Tamer Mohamed Mahmoud, Mohammed Ayad Alboreadi, Amr Gamal Fouad, Nada H Mohammed, Amany Belal, Fahad H Baali, Nisreen Khalid Aref Albezrah, Mohammed S Alharthi, Sherif Faysal Abdelfattah Khalil, Fatma I Abo El-Ela\",\"doi\":\"10.1080/1061186X.2025.2573051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Carvedilol (CRD) is an oral beta-adrenergic antagonist approved for treating heart failure (HF). 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Improving the Therapeutic Efficacy and Bioavailability of Carvedilol for Control of Diabetes-Associated Heart Failure: In Vitro and In Vivo Characterization.
Carvedilol (CRD) is an oral beta-adrenergic antagonist approved for treating heart failure (HF). However, due to its short half-life and poor solubility, CRD has limited bioavailability and effectiveness. This study aimed to develop a nasal spray of CRD-novasomes (CLN) to enhance CRD's sustainability, targeting, bioavailability, and efficacy as a therapy for diabetes mellitus-associated HF (DMHF). Several CLN formulations were created using Box-Behnken design and characterized in vitro to identify the optimized formulation, which was later evaluated in vivo using an experimental DMHF rat model. The selected optimized CLN formulation consists of 30.079 mg of oleic acid, 56.897 mg of Span 60, and 60 mg of cholesterol. The optimized CLN demonstrated significant improvements over free CRD, enhancing CRD's sustainability and permeability by 71.39% and 6.08-fold, respectively. When compared to oral free CRD, the nasal CLN increased the bioavailability and target efficiency of CRD by 5.74-fold and 4.24-fold, respectively. In relation to DMHF positive control, the nasal CLN significantly lowered glucose, LDH, and CK-MB levels by 93.68%, 94.29%, and 96.50%, respectively, showcasing its efficacy. Histopathological and toxicity studies further validated the activity and safety of the optimized CLN. These findings indicate that the nasal CLN spray shows potential as a therapy for DMHF.
期刊介绍:
Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs.
Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.