Abstract
Background: The mucolytic N-acetylcysteine (NAC) is used to control the excessive mucus secretion if mucus is the underlying cause of broncho-constriction. Its major drawbacks are poor bioavailability due to extensive first pass effect, poor lipophilicity, high protein binding and offensive odor.
Methods: For minimizing above shortcomings of NAC, in present study thioester (A1) prodrug of NAC was synthesized by conventional as well as microwave-assisted methods. Release studies of A-1 were carried out using HPLC and pharmacological evaluation was performed in ovalbumin-induced model of pulmonary inflammation in Sprague dawley rats.
Results: A-1 was found to be stable in HCl buffer, phosphate buffer, stomach homogenates but furnished 30% NAC in 6h and 1.7% of NAC in 4h when incubated with small intestinal and liver homogenates respectively. Upon oral administration of A-1 to rats, 4.85% NAC was detected in blood at 8h. Urine samples pooled over a period of 24h exhibited 0.75% NAC while negligible concentration was found in 24 h pooled samples of feces.
Conclusion: The findings of this preliminary investigation demonstrated significant effects of thioester prodrug A-1 as compared to NAC through reduction of lung inflammation, airway eosinophilia and reversal of lung function parameters in ovalbumin- challenged rats at half the equimolar dose of NAC. Interestingly masking thiol group through thioester formation resulted in odorless prodrug. We propose that thioester prodrug using palmitic acid as a carrier is a promising strategy to enhance bioavailability of NAC by increasing its lipophilicity/ absorption and minimizing its first pass metabolism.
Keywords: N-acetylcysteine, odor masking, ovalbumin, palmitic acid, poor bioavailability, thioester prodrug, thiol.
Current Drug Delivery
Title:Novel Thioester Prodrug of N-acetylcysteine for Odor Masking and Bioavailability Enhancement
Volume: 13 Issue: 4
Author(s): Neha V. Bhilare, Suneela S. Dhaneshwar, Akanksha J. Sinha, Amit D. Kandhare and Subhash L. Bodhankar
Affiliation:
Keywords: N-acetylcysteine, odor masking, ovalbumin, palmitic acid, poor bioavailability, thioester prodrug, thiol.
Abstract: Background: The mucolytic N-acetylcysteine (NAC) is used to control the excessive mucus secretion if mucus is the underlying cause of broncho-constriction. Its major drawbacks are poor bioavailability due to extensive first pass effect, poor lipophilicity, high protein binding and offensive odor.
Methods: For minimizing above shortcomings of NAC, in present study thioester (A1) prodrug of NAC was synthesized by conventional as well as microwave-assisted methods. Release studies of A-1 were carried out using HPLC and pharmacological evaluation was performed in ovalbumin-induced model of pulmonary inflammation in Sprague dawley rats.
Results: A-1 was found to be stable in HCl buffer, phosphate buffer, stomach homogenates but furnished 30% NAC in 6h and 1.7% of NAC in 4h when incubated with small intestinal and liver homogenates respectively. Upon oral administration of A-1 to rats, 4.85% NAC was detected in blood at 8h. Urine samples pooled over a period of 24h exhibited 0.75% NAC while negligible concentration was found in 24 h pooled samples of feces.
Conclusion: The findings of this preliminary investigation demonstrated significant effects of thioester prodrug A-1 as compared to NAC through reduction of lung inflammation, airway eosinophilia and reversal of lung function parameters in ovalbumin- challenged rats at half the equimolar dose of NAC. Interestingly masking thiol group through thioester formation resulted in odorless prodrug. We propose that thioester prodrug using palmitic acid as a carrier is a promising strategy to enhance bioavailability of NAC by increasing its lipophilicity/ absorption and minimizing its first pass metabolism.
Export Options
About this article
Cite this article as:
V. Bhilare Neha, S. Dhaneshwar Suneela, J. Sinha Akanksha, D. Kandhare Amit and L. Bodhankar Subhash, Novel Thioester Prodrug of N-acetylcysteine for Odor Masking and Bioavailability Enhancement, Current Drug Delivery 2016; 13 (4) . https://dx.doi.org/10.2174/1567201812666150904144607
DOI https://dx.doi.org/10.2174/1567201812666150904144607 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...read more
- Author Guidelines
- 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
-
Heat Shock Proteins and Ion Channels. Functional Interactions and Therapeutic Consequences
Current Pharmaceutical Biotechnology The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies
Current Neuropharmacology Effects of Brain IKKβ Gene Silencing by Small Interfering RNA on P-Glycoprotein Expression and Brain Damage in the Rat Kainic Acid-Induced Seizure Model
CNS & Neurological Disorders - Drug Targets Synthesis of Poison-Frog Alkaloids and Their Pharmacological Effects at Neuronal Nicotinic Acetylcholine Receptors
Current Chemical Biology Patent Selections:
Recent Patents and Topics on Imaging (Discontinued) Chemistry and Biology of Cyperus scariosus: An Overview
Current Chemical Biology Approaching Neurological Diseases to Reduce Mobility Limitations in Older Persons
Current Pharmaceutical Design Strategy for a Genetic Assessment of Antipsychotic and Antidepressant- Related Proarrhythmia
Current Medicinal Chemistry Neuropeptides as Therapeutic Targets to Combat Stress-Associated Behavioral and Neuroendocrinological Effects
CNS & Neurological Disorders - Drug Targets Biomedical Application of Polymers: A Case Study of Non-CNS Drugs Becoming CNS Acting Drugs
Central Nervous System Agents in Medicinal Chemistry The Neurotachykinin NK1 Receptor – A Novel Target for Diagnostics and Therapy
Current Molecular Imaging (Discontinued) An Update on GABAρ Receptors
Current Neuropharmacology Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) Genes, Blame and Loss of Control: is there a Place in Criminal Law for a ‘Genetic Defense’?
Recent Advances in DNA & Gene Sequences (Discontinued) New Therapeutic Strategies in Perinatal Stroke
Current Drug Targets - CNS & Neurological Disorders Valproic acid, A Potential Inducer of Osteogenesis in Mouse Mesenchymal Stem Cells
Current Molecular Pharmacology α7 Nicotinic Acetylcholine Receptor Mediated Neuroprotection in Parkinson’s Disease
Current Drug Targets Methylphenidate (Ritalin): What Makes it so Widely Prescribed During the Last 60 Years?
Current Drug Therapy A Comprehensive Investigation of Molecular Signatures and Pathways Linking Alzheimer’s Disease and Epilepsy <i>via</i> Bioinformatic Approaches
Current Alzheimer Research Antiepileptic Drugs During Pregnancy: Pharmacokinetics and Transplacental Transfer
Current Pharmaceutical Biotechnology