Abstract
Background: Hydrogels are the polymeric network, which can retain large amount of water. Thus, these delivery systems always remained an issue of intensive research among the scientist fraternity.
Objective: In this piece of work, we have reconnoitered the significance of the PEGylated anticancer loaded drug onto poloxamer based thermoresponsive injectable hydrogel to understand the role of delivery system.
Method: To accomplish the objective, firstly it was necessary to improve the solubility of the melphalan, achieved by PEGylation of the drug with two grades of linear methoxy poly ethylene glycol (M-PEG), viz. M-PEG 2000 and 5000 Da to form a PEGylated melphalan conjugate (MLPEG). In our previous study, we have found that the prepared conjugates were efficiently enhanced the solubility of the melphalan and significantly reduced the hemolytic effect due to the presence of the PEG chains. Thus, in the present work, the prepared conjugates (MLPEG 5000 and 2000) were loaded to the thermosensitive Poloxamer 407 (P407) gel to produce an injectable hydrogel (MPX). To underline the reduction of the initial burst of the drug at the site of action, one of the hydrogels was prepared in the presence of the NaCl salt.
Results: This in turn, tightened the PEO chains and remarkably reduced the drug’s initial burst from the delivery system as only 43 % of drug was released during 2 hours from MPX-CG hydrogel. Moreover, a lower diffusion coefficient (D) was noticed for MPX-CG gel as compared with MPX-7.4 gel. To confirm the depot formation, prepared hydrogels were administered to Wistar rats via subcutaneous and intramuscular routes.
Conclusion: Thus, P407 based injectable hydrogel could play an important role for the delivery of a low dose-alkylating agent with reduced host cytotoxicity.
Keywords: Diffusion coefficient. Injectable, In situ, MCF-7, Melphalan, Poloxamer, Thermoreversible.
Current Drug Delivery
Title:Understanding the Role of Poloxamer 407 based Thermoreversible In Situ Gelling Hydrogel for Delivery of PEGylated Melphalan Conjugate
Volume: 13 Issue: 4
Author(s): Amit Alexander, Swarnlata Saraf and Shailendra Saraf
Affiliation:
Keywords: Diffusion coefficient. Injectable, In situ, MCF-7, Melphalan, Poloxamer, Thermoreversible.
Abstract: Background: Hydrogels are the polymeric network, which can retain large amount of water. Thus, these delivery systems always remained an issue of intensive research among the scientist fraternity.
Objective: In this piece of work, we have reconnoitered the significance of the PEGylated anticancer loaded drug onto poloxamer based thermoresponsive injectable hydrogel to understand the role of delivery system.
Method: To accomplish the objective, firstly it was necessary to improve the solubility of the melphalan, achieved by PEGylation of the drug with two grades of linear methoxy poly ethylene glycol (M-PEG), viz. M-PEG 2000 and 5000 Da to form a PEGylated melphalan conjugate (MLPEG). In our previous study, we have found that the prepared conjugates were efficiently enhanced the solubility of the melphalan and significantly reduced the hemolytic effect due to the presence of the PEG chains. Thus, in the present work, the prepared conjugates (MLPEG 5000 and 2000) were loaded to the thermosensitive Poloxamer 407 (P407) gel to produce an injectable hydrogel (MPX). To underline the reduction of the initial burst of the drug at the site of action, one of the hydrogels was prepared in the presence of the NaCl salt.
Results: This in turn, tightened the PEO chains and remarkably reduced the drug’s initial burst from the delivery system as only 43 % of drug was released during 2 hours from MPX-CG hydrogel. Moreover, a lower diffusion coefficient (D) was noticed for MPX-CG gel as compared with MPX-7.4 gel. To confirm the depot formation, prepared hydrogels were administered to Wistar rats via subcutaneous and intramuscular routes.
Conclusion: Thus, P407 based injectable hydrogel could play an important role for the delivery of a low dose-alkylating agent with reduced host cytotoxicity.
Export Options
About this article
Cite this article as:
Alexander Amit, Saraf Swarnlata and Saraf Shailendra, Understanding the Role of Poloxamer 407 based Thermoreversible In Situ Gelling Hydrogel for Delivery of PEGylated Melphalan Conjugate, Current Drug Delivery 2016; 13 (4) . https://dx.doi.org/10.2174/1567201813666160204114000
DOI https://dx.doi.org/10.2174/1567201813666160204114000 |
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
-
Role of Advanced Glycation End Products in Diabetic Neuropathy
Current Pharmaceutical Design Metal Catalyzed Oxidation of Alpha-Synuclein – A Role for Oligomerization in Pathology?
Current Alzheimer Research Investigation on the Molecular Interactions Stabilizing the Structure of α-synuclein Fibril: An In silico Study
Central Nervous System Agents in Medicinal Chemistry Cell Arrest and Apoptosis Induced by the Next Generation of Vanadium Based Drugs: Action Mechanism to Structure Relation and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry Gynecomastia in Infants, Children, and Adolescents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Aβ(1-42) Aggregates into Non-Toxic Amyloid Assemblies in the Presence of the Natural Polyphenol Oleuropein Aglycon
Current Alzheimer Research Histone Deacetylase Inhibitors: An Attractive Strategy for Cancer Therapy
Current Medicinal Chemistry Andrographolide Mitigates Unfolded Protein Response Pathway and Apoptosis Involved in Chikungunya Virus Infection
Combinatorial Chemistry & High Throughput Screening Synthetic Lipoproteins as Carriers for Drug Delivery
Current Medicinal Chemistry Spectroscopic Characterization of a Pyridine Alkaloid from an Endophytic Strain of the Fusarium incarnatum-equiseti Species Complex
Current Bioactive Compounds Structural Diversity of Neuritogenic Substances and their Application Perspective
Mini-Reviews in Medicinal Chemistry Tumor Specific Novel Taxoid-Monoclonal Antibody Conjugates
Current Medicinal Chemistry CASC15: A Tumor-Associated Long Non-Coding RNA
Current Pharmaceutical Design Src Kinase Inhibitors: An Update on Patented Compounds
Current Medicinal Chemistry PSEN1 Promoter Demethylation in Hyperhomocysteinemic TgCRND8 Mice is the Culprit, not the Consequence
Current Alzheimer Research Production and Application of Copper Radiopharmaceuticals
Current Radiopharmaceuticals The Sam Domain of EphA2 Receptor and its Relevance to Cancer: A Novel Challenge for Drug Discovery?
Current Medicinal Chemistry Natural Product-Derived Small Molecule Activators of Hypoxia-Inducible Factor-1 (HIF-1)
Current Pharmaceutical Design Cervical Cancer Diagnosis: Insights into Biochemical Biomarkers and Imaging Techniques
Combinatorial Chemistry & High Throughput Screening Biotransformation of Microcystins in Eukaryotic Cells - Possible Future Research Directions
Mini-Reviews in Medicinal Chemistry