Synthesis, Characteristics and Potential Application of Poly(β-Amino Ester Urethane)-Based Multiblock Co-Polymers as an Injectable, Biodegradable and pH/Temperature-Sensitive Hydrogel System (original) (raw)
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Acta Biomaterialia, 2011
An injectable biodegradable pH/temperature-sensitive oligo(b-amino ester urethane) (OAEU) was synthesized. The OAEU was synthesized by addition polymerization between the isocyanate groups of 1,6diisocyanato hexamethylene and the hydroxyl groups of a synthesized monomer piperazine dihydroxyl amino ester (monomer PDE) in chloroform in the presence of dibutyltin dilaurate as a catalyst. The synthesized OAEU was characterized by 1 H NMR spectroscopy, Fourier transform infrared spectroscopy and gel permeation chromatography. The aqueous solutions of OAEU showed a sol-to-gel-to-sol phase transition as a function of temperature and pH. The gel window covered the physiological conditions (37°C, pH 7.4) and could be controlled by changing the OAEU concentration. After a subcutaneous injection of the OAEU solution into Sprague-Dawley rats, a gel formed rapidly in situ and remained in the body for more than 2 weeks. The in vitro cytotoxicity test and in vitro degradation showed that the OAEU hydrogel was non-cytotoxic and biodegradable. The in vitro release of doxorubicin from this OAEU hydrogel was sustained for more than 10 days. This injectable biodegradable pH/temperature-sensitive OAEU hydrogel is a potential candidate as a drug/protein carrier and in biomedical applications.
Characterisation and controlled drug release from novel drug-loaded hydrogels
European Journal of Pharmaceutics and Biopharmaceutics, 2008
Hydrogel based devices belong to the group of swelling controlled drug delivery systems. Temperature responsive poly(N-isopropylacrylamide)-poly(vinylpyrrolidinone) random copolymers were produced by free radical polymerisation, using 1-hydroxycyclohexylphenyketone as an ultraviolet-light sensitive initiator, and poly(ethylene glycol) dimethacrylate as the crosslinking agent (where appropriate). The hydrogels were synthesised to have lower critical solution temperatures (LCST) near body temperature, which is favourable particularly for 'smart' drug delivery applications. Two model drugs (diclofenac sodium and procaine HCl) were entrapped within these xerogels, by incorporating the active agents prior to photopolymerisation. The properties of the placebo samples were contrasted with the drug-loaded copolymers at low levels of drug integration. Modulated differential scanning calorimetry (MDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscopy (AFM) were used to investigate the influence of the drugs incorporated on the solid-state properties of the xerogels. MDSC and swelling studies were carried out to ascertain their effects on the LCST and swelling behaviour of the hydrated samples. In all cases, drug dissolution analysis showed that the active agent was released at a slower rate at temperatures above the phase transition temperature. Finally, preliminary in vitro cytotoxicity evaluations were performed to establish the toxicological pattern of the gels.
Injectable polymeric hydrogels for the delivery of therapeutic agents: A review
European Polymer Journal, 2015
Since drug delivery systems have become one of the most promising areas of human health related research, the applications of biomaterials such as hydrogels have been widely investigated. Possessing unique hydrophilic, biocompatible network structures and the ability to form solid-like gel states once administered, injectable hydrogels facilitate the encapsulation and release of therapeutic agents, including drugs, proteins, genes and cells, in a controllable manner. A wide and diverse range of techniques have been used to generate hydrogels, from chemical cross-linking, such as photo-polymerization, click chemistry, enzyme-catalyzed reactions, Schiff's base reactions, and thiol-based Michael reactions, to physical cross-linking induced by temperature, pH, ionic interaction, guesthost inclusion, stereo-complexation or complementary binding. This review covers the utilization of various injectable hydrogel systems for the delivery of therapeutic agents from the viewpoint of cross-linking methods.
As A Review on Hydrogels as Drug Delivery in the Pharmaceutical Field
Hydrogel is a network of polymer chains that are water-insoluble, sometimes found as a colloidal gel in which water is the dispersion medium. Hydrogels are crosslinked polymer networks that absorb substantial amounts of aqueous solutions. Due to their high water content, these gels resemble natural living tissue more than any other type of synthetic biomaterial. Several techniques have been reported for the synthesis of hydrogels like co polymerization/crosslinking of co-monomers using multifunctional co-monomer, which acts as crosslinking agent. Chemical initiator initiates the polymerization reaction. Some applications are used of hydrogels in human body. Some environmental variables, such as low pH and elevated temperatures, are found in the body. For this reason, either pH-sensitive and/or temperature sensitive hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosens...
Applications of Hydrogels in Drug Delivery: A Review
Target specific drug delivery has gained increased importance in recent years. The polymeric hydrogels has recently been playing a more important role as target specific drug delivery devices. These hydrogels can be synthesized to respond to various physiological stimuli in the body, for example pH, ionic strength and temperature. This article briefly summarizes drug delivery applications of hydrogels.
Journal of Biomaterials Science, Polymer Edition, 2014
The objective of the present study was to develop 2-hydroxypropyl methacrylate-co-polyethylene methacrylate [p(HPMA-co-PEG-MEMA)] hydrogels that are able to efficiently entrap doxorubicin for the application of loco-regional control of the cancer disease. Systemic chemotherapy provides low clinical benefit while localized chemotherapy might provide a therapeutic advantage. In this study, effects of hydrogel properties such as PEG chains length, cross-linking density, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. In addition, the characterization of the hydrogel formulations was conducted with swelling experiments, permeability tests, Fourier transform infrared, SEM, and contact angle studies. In these drughydrogel systems, doxorubicin contains amine group that can be expected a strong Lewis acid-base interaction between drug and polar groups of PEG chains, thus the drug was released in a timely fashion with an electrostatic interaction mechanism. It was observed that doxorubicin release from the hydrogel formulations decreased when the density of cross-linking, and drug/polymer ratio were increased while an increase in the PEG chains length of the macro-monomer (i.e. PEG-MEMA) in the hydrogel system was associated with an increase in water content and doxorubicin release. The biocompatibility of the hydrogel formulations has been investigated using two measures: cytotoxicity test (using lactate dehydrogenase assay) and major serum proteins adsorption studies. Antitumor activity of the released doxorubicin was assessed using a human SNU398 human hepatocellular carcinoma cell line. It was observed that doxorubicin released from all of our hydrogel formulations which remained biologically active and had the capability to kill the tested cancer cells.
Hydrogels Used As A Potential Drug Delivery System: A Review
International Journal of Pharmaceutical & Biological …, 2011
Hydrogels, the swellable polymeric materials have been widely investigated as the carrier for drug delivery systems. These biomaterials have gained attention owing to their peculiar characteristics like swelling in aqueous medium, pH and temperature sensitivity or sensitivity towards other stimuli. Hydrogels being biocompatible materials have been recognized to function as drug protectors, especially for peptides and proteins, from in-vivo environment. Also, these swollen polymers are helpful as targetable carriers for bioactive drugs with tissue specificity. Hydrogels are presently under investigation as a delivery system for bioactive molecules, because of their similar physical properties as that of living tissue, which is due to their high water content, soft and rubbery consistency, and low interfacial tension with water or biological fluids. This review presents an overview to the advances in hydrogel based drug delivery that have became the interest of most researchers.
A stimuli-responsive hydrogel for doxorubicin delivery
Biomaterials, 2010
The goal of this study was to develop a polymeric carrier for delivery of anti-tumor drugs and sustained release of these agents in order to optimize anti-tumor activity while minimizing systemic effects. We used oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels modified with small negatively charged molecules, sodium methacrylate (SMA), for delivery of doxorubicin (DOX). SMA at different concentrations was incorporated into the OPF hydrogel with a photo-crosslinking method. The resulting hydrogels exhibited sensitivity to the pH and ionic strength of the surrounding environment. Our results revealed that DOX was bound to the negatively charged hydrogel through electrostatic interaction and was released in a timely fashion with an ion exchange mechanism. Release kinetics of DOX was directly correlated to the concentration of SMA in the hydrogel formulations. Anti-tumor activity of the released DOX was assessed using a human osteosarcoma cell line. Our data revealed that DOX released from the modified, charged hydrogels remained biologically active and had the capability to kill cancer cells. In contrast, control groups of unmodified OPF hydrogels with or without DOX did not exhibit any cytotoxicity. This study demonstrates the feasibility of using SMA-modified OPF hydrogels as a potential carrier for chemotherapeutic drugs for cancer treatments.
Journal of Biomedical Materials Research, 2002
A class of new biodegradable hydrogels based on poly(ethylene glycol) methacrylate-graft-poly(glutamic acid) and poly(ethylene glycol) dimethacrylate was synthesized by photoinduced polymerization. Because all the polymeric constituents were highly hydrophilic, crosslinking could be performed in aqueous solutions. This type of crosslinked hydrogel was prepared by modifying a select number of acidic side-groups on poly(glutamic acid) with poly(ethylene glycol) methacrylate. These modified chains were then crosslinked in the presence of poly(ethylene glycol) dimethacrylate under a photoinduced polymerization at a wavelength of 365 nm. Swelling experiments were conducted to study the crosslinking density, pH-responsive behavior, and degradation of the hydrogel. Results showed that the degree of swelling of this type of hydrogels increased as the crosslinker concentration (or density) was reduced. Because of the presence of acidic side chains on poly-(glutamic acid), swelling behavior was found to be pHresponsive, increasing at high pH in response to the increase in the amount of ionized acidic side chains. The degradation rate of these hydrogels also varied with pH. More rapid degradation was observed under stronger alkaline conditions because of the hydrolysis of the ester bonds between the crosslinker and the polymer backbone. Practically useful degradation rates could be achieved for such hydrogels under physiological conditions. Drug release rates from these hydrogels were found to be proportional to the protein molecular weight and the crosslinker density; increasing at lower protein molecular weight or crosslinker density. The preliminary findings presented in this article suggest that this class of biodegradable hydrogels could be an attractive avenue for drug delivery applications. The specific photoinduced crosslinking chemistry used would permit hydrogels to be synthesized in existence of the entrapped macromolecular drugs including peptides, proteins, and cells. In addition, the rapid feature of this polymerization procedure along with the ability to perform hydrogel synthesis and drug loading in an aqueous environment would offer great advantages in retaining drug activity during hydrogel synthesis.