Abstract
GLM-7 is a novel anti-leukemia drug in the pre-clinical study. The previous study shows that GLM-7 is a poorly water-soluble drug with low oral bioavailability. In this study, we employed the self-emulsifying drug delivery system (SEDDS) to improve the oral bioavailability of GLM-7. The GLM-7 SEDDS formulation was prepared using MCT as oil, ovolecithin as surfactant and Transcutol as co-surfactant, and the formulation parameters were optimized by the response surface methodology. The optimized GLM-7 SEDDS formulation showed a stable liquid state, and can automatically emulsify to form the isotropic emulsion once exposure to the water phase. The generated emulsion showed the spherical shape, and had an average size of about 399nm and a zeta potential of about -42mV. Compared to the GLM-7 dissolution less than 1.4% from pure GLM-7 powder (reference), the GLM-7 SEDDS formulation could remarkably enhance the in vitro dissolution to 83% in the medium of 0.1N HCL. The in vivo oral bioavailability of GLM-7 SEDDS formulation was investigated in beagle dogs. The results demonstrated that the GLM-7 SEDDS formulation significantly enhanced the plasma concentrations of GLM-7, and the Cmax reached to 878ng/ml and was 9.2 folds as high as the Cmax 95.85ng/ml of reference. Moreover, the area under the curve (AUC) of GLM-7 SEDDS formulation was 13.6 times higher than that of reference, which suggested that the SEDDS formulation remarkably increased the oral bioavailability of GLM-7.
Keywords: Bioavailability, dissolution, oral drug delivery, poorly water-soluble drugs, self-emulsifying drug delivery system.
Graphical Abstract
Current Drug Delivery
Title:Enhancing in vivo Bioavailability in Beagle Dogs of GLM-7 as a Novel Anti-Leukemia Drug through a Self-Emulsifying Drug Delivery System for Oral Delivery
Volume: 13 Issue: 1
Author(s): Yuli Wang, Ning Yu, Rui Guo, Meiyan Yang, Li Shan, Wei Huang, Wei Gong, Shuai Shao, Xiaoping Chen and Chunsheng Gao
Affiliation:
Keywords: Bioavailability, dissolution, oral drug delivery, poorly water-soluble drugs, self-emulsifying drug delivery system.
Abstract: GLM-7 is a novel anti-leukemia drug in the pre-clinical study. The previous study shows that GLM-7 is a poorly water-soluble drug with low oral bioavailability. In this study, we employed the self-emulsifying drug delivery system (SEDDS) to improve the oral bioavailability of GLM-7. The GLM-7 SEDDS formulation was prepared using MCT as oil, ovolecithin as surfactant and Transcutol as co-surfactant, and the formulation parameters were optimized by the response surface methodology. The optimized GLM-7 SEDDS formulation showed a stable liquid state, and can automatically emulsify to form the isotropic emulsion once exposure to the water phase. The generated emulsion showed the spherical shape, and had an average size of about 399nm and a zeta potential of about -42mV. Compared to the GLM-7 dissolution less than 1.4% from pure GLM-7 powder (reference), the GLM-7 SEDDS formulation could remarkably enhance the in vitro dissolution to 83% in the medium of 0.1N HCL. The in vivo oral bioavailability of GLM-7 SEDDS formulation was investigated in beagle dogs. The results demonstrated that the GLM-7 SEDDS formulation significantly enhanced the plasma concentrations of GLM-7, and the Cmax reached to 878ng/ml and was 9.2 folds as high as the Cmax 95.85ng/ml of reference. Moreover, the area under the curve (AUC) of GLM-7 SEDDS formulation was 13.6 times higher than that of reference, which suggested that the SEDDS formulation remarkably increased the oral bioavailability of GLM-7.
Export Options
About this article
Cite this article as:
Wang Yuli, Yu Ning, Guo Rui, Yang Meiyan, Shan Li, Huang Wei, Gong Wei, Shao Shuai, Chen Xiaoping and Gao Chunsheng, Enhancing in vivo Bioavailability in Beagle Dogs of GLM-7 as a Novel Anti-Leukemia Drug through a Self-Emulsifying Drug Delivery System for Oral Delivery, Current Drug Delivery 2016; 13 (1) . https://dx.doi.org/10.2174/1570159X13666150713173838
DOI https://dx.doi.org/10.2174/1570159X13666150713173838 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Bax Inhibitor-1 (BI-1) Family in Apoptosis and Tumorigenesis
Current Molecular Medicine Imaging Virus-Associated Cancer
Current Pharmaceutical Design Dietary Polyphenols for Prostate Cancer Therapy
Current Bioactive Compounds Protein Tyrosine Phosphatases: Strategies for Distinguishing Proteins in a Family Containing Multiple Drug Targets and Anti-Targets
Current Pharmaceutical Design Synthesis, Anti-inflammatory and Molecular Docking Study of Schiff Bases Containing Methanesulphonyl Pharmacophore
Letters in Drug Design & Discovery Zinc and Copper Homeostasis in Head and Neck Cancer: Review and Meta-Analysis
Current Medicinal Chemistry The Potential for Targeting Oncogenic WNT/β -Catenin Signaling in Therapy
Current Drug Targets Ghrelin, A Novel Peptide Hormone in the Regulation of Energy Balance and Cardiovascular Function
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) VIP and Drug Design
Current Pharmaceutical Design Vitamins for Cancer Prevention and Treatment: An Insight
Current Molecular Medicine Antimicrobial and Antioxidant Activity of Micromeria Bentham Species
Current Pharmaceutical Design Interaction of Probenecid with the Breast Cancer Resistance Protein Transporter (BCRP/ABCG2)
Letters in Drug Design & Discovery Update on COX-2 Selective Inhibitors: Chemical Classification, Side Effects and their Use in Cancers and Neuronal Diseases
Current Topics in Medicinal Chemistry Desensitization Protocol for Rituximab-Induced Serum Sickness
Current Drug Safety Metal Toxicity and Speciation: A Review
Current Medicinal Chemistry Recent Advances in Receptor-Targeted Fluorescent Probes for In Vivo Cancer Imaging
Current Medicinal Chemistry The Impact of Folate Status on the Efficacy of Colorectal Cancer Treatment
Current Drug Metabolism Signal Transduction Pathways of Inflammatory Gene Expressions and Therapeutic Implications
Current Pharmaceutical Design Metabolic Pathways of Ochratoxin A
Current Drug Metabolism Inhibitors of the Microsomal Prostaglandin E2 Synthase-1 as Alternative to Non Steroidal Anti-Inflammatory Drugs (NSAIDs) – A Critical Review
Current Medicinal Chemistry