![conference banner](/images/conference-banner.jpeg)
Abstract
Novel amide conjugates of the NSAID naproxen (NAP, 1) with short-chain α-alkylamino acids (C4 to C6 alkyl chain) were synthesized through a carbodiimide (EDAC)-assisted coupling reaction and evaluated as dermal prodrugs of NAP. The 2-α-aminobutyl derivative (2) showed lipophilicity similar to that of NAP, while the higher homologues (3) and (4) were more lipophilic than the parent drug, as assessed by CLogP and HPLC methods. The chemical and enzymatic hydrolysis of these compounds was evaluated in aqueous buffer solution (pH 7.4) and 80% human plasma. All compounds showed a good chemical stability (t1 / 2 = 88-133 h) but underwent a rapid enzymatic hydrolysis to NAP (t1 / 2_around 3 h). The bioconversion of prodrugs into NAP was confirmed by an in vivo test, since i.p. administration of compounds 2-4 to mice gave a similar analgesic response than the parent drug. In vitro skin permeation experiments were performed using adult human SCE samples mounted in Franz-type diffusion cells. The butyl derivative 2 that showed an increased aqueous solubility compared to NAP gave a 5-fold improvement of skin permeation compared to NAP. In conclusion, the conjugate 2 could be regarded as a good candidate to improve NAP topical delivery and will be further studied as a prodrug for topical administration of this drug.
Keywords: naproxen, prodrugs, 2-alkylamino acids, lipophilicity, dermal delivery
Current Drug Delivery
Title: Synthesis and In Vitro Skin Permeation of Naproxen Conjugates with α- Alkylamino Acids
Volume: 2 Issue: 2
Author(s): Rosario Pignatello, Lucia Montenegro, Annalisa H.S. Stancampiano, Antonina Puleo and Giovanni Puglisi
Affiliation:
Keywords: naproxen, prodrugs, 2-alkylamino acids, lipophilicity, dermal delivery
Abstract: Novel amide conjugates of the NSAID naproxen (NAP, 1) with short-chain α-alkylamino acids (C4 to C6 alkyl chain) were synthesized through a carbodiimide (EDAC)-assisted coupling reaction and evaluated as dermal prodrugs of NAP. The 2-α-aminobutyl derivative (2) showed lipophilicity similar to that of NAP, while the higher homologues (3) and (4) were more lipophilic than the parent drug, as assessed by CLogP and HPLC methods. The chemical and enzymatic hydrolysis of these compounds was evaluated in aqueous buffer solution (pH 7.4) and 80% human plasma. All compounds showed a good chemical stability (t1 / 2 = 88-133 h) but underwent a rapid enzymatic hydrolysis to NAP (t1 / 2_around 3 h). The bioconversion of prodrugs into NAP was confirmed by an in vivo test, since i.p. administration of compounds 2-4 to mice gave a similar analgesic response than the parent drug. In vitro skin permeation experiments were performed using adult human SCE samples mounted in Franz-type diffusion cells. The butyl derivative 2 that showed an increased aqueous solubility compared to NAP gave a 5-fold improvement of skin permeation compared to NAP. In conclusion, the conjugate 2 could be regarded as a good candidate to improve NAP topical delivery and will be further studied as a prodrug for topical administration of this drug.
Export Options
About this article
Cite this article as:
Pignatello Rosario, Montenegro Lucia, Stancampiano H.S. Annalisa, Puleo Antonina and Puglisi Giovanni, Synthesis and In Vitro Skin Permeation of Naproxen Conjugates with α- Alkylamino Acids, Current Drug Delivery 2005; 2 (2) . https://dx.doi.org/10.2174/1567201053585976
DOI https://dx.doi.org/10.2174/1567201053585976 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advancements in Robotic and AI-Based Drug Discovery and Delivery for Neurological Disorders
Neurological disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, and brain tumors, pose significant challenges in drug delivery due to the blood-brain barrier's intricate structure and the complexity of neuronal networks. Traditional drug delivery methods often fall short in reaching therapeutic concentrations within the central nervous system, limiting treatment efficacy and ...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 to 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
Extracellular vesicles as drug delivery systems
Extracellular vesicles (EVs) are membranous vesicles released from almost all types of cells into extracellular space. EVs are categorized into different types including exosome (~30-150 nm), microvesicle or microparticle (~100-1,000 nm), apoptotic body (~1,000-5,000 nm), and others produced by different mechanisms. Since EVs bear the molecules (e.g., specific lipids, carbohydrates, ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Essential Roles of Intracellular Calcium Release Channels in Muscle, Brain, Metabolism, and Aging
Current Molecular Pharmacology Structural Disorder within the Measles Virus Nucleoprotein and Phosphoprotein
Protein & Peptide Letters Modulation of Expression and Activity of ABC Transporters by the Phytoestrogen Genistein. Impact on Drug Disposition
Current Medicinal Chemistry TMEM16A/B Associated CaCC: Structural and Functional Insights
Protein & Peptide Letters Gene Electrotransfer in 3D Reconstructed Human Dermal Tissue
Current Gene Therapy Old and New Antiepileptic Drugs for the Treatment of Idiopathic Generalized Epilepsies
Current Clinical Pharmacology Activated T Lymphocytes in Type 2 Diabetes: Implications From in Vitro Studies
Current Drug Targets Enzyme Mediated Baeyer-Villiger Oxidations
Current Organic Chemistry Editorial (Thematic Issue: Molecular and Cellular Engineering Approaches for Neurological Disorders, Diseases, and Injuries Involved the Central and Peripheral Nervous Systems)
CNS & Neurological Disorders - Drug Targets Novel Research Strategies of Benzimidazole Derivatives: A Review
Mini-Reviews in Medicinal Chemistry Chemopreventive and Chemotherapeutic Potential of Curcumin in Breast Cancer
Current Drug Targets Antiviral Treatment of HCV Carriers with Persistently Normal ALT Levels
Mini-Reviews in Medicinal Chemistry Upstream Processing of Plasmid DNA for Vaccine and Gene Therapy Applications
Recent Patents on Biotechnology Differential Regulation of Protein- and Polysaccharide-Specific Ig Isotype Production In Vivo in Response to Intact Streptococcus pneumoniae
Current Protein & Peptide Science Therapeutic Potential of Janus Kinase 3 (JAK3) Inhibitors
Current Pharmaceutical Design Neuroprotective Potential of Adenyl Cyclase/cAMP/CREB and Mitochondrial CoQ10 Activator in Amyotrophic Lateral Sclerosis Rats
Current Bioactive Compounds Prostacyclin Synthase Gene: Genetic Polymorphisms and Prevention of Some Cardiovascular Diseases
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Leptomeningeal Metastasis: Challenges in Diagnosis and Treatment
Current Cancer Therapy Reviews G4-Interacting DNA Helicases and Polymerases: Potential Therapeutic Targets
Current Medicinal Chemistry Therapeutic Proteins for Treatment of Corneal Epithelial Defects
Current Medicinal Chemistry