The Release of Doxorubicin’s Active Ingredient from the Hydrogels with Poly (HEMA/Acrylamide/ Itaconic acid) and Their Biological Function (original) (raw)
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Indian Journal of Pharmaceutical Education and Research, 2019
Poly (HEMA/acrylamide/ methyl methacrylate) (PHAM) and Poly (Acrylamide/ methyl methacrylate)(PAM) polymers were synthesized for using in the release of Doxorubicin drug. Poly (HEMA/acrylamide/methyl methacrylate) (PHAM) and Poly (Acrylamide/methyl methacrylate) (PAM) composite hydrogels were prepared by a radical addition reaction in aqueous media formed by HEMA, acrylamide, and methacrylamide, with the presence of N,N'-methylenebisacrylamide. The characterization of the polymer was performed by FTIR analysis. Swelling and drug absorption properties of the polymers were analyzed in distilled water. Polymers' toxic effects were investigated by XTT assay. It has been observed that the entire drug, which was added to the solution with 1 g of polymer, was absorbed for 3.5 h. The absorption of these polymers was found quite high. PHAM polymer showed >800% swelling and PAM polymer showed >600% at 600 min. PHAM polymer was less toxic than PAM polymer. These results, this new polymer is very suitable for the release of Doxorubicin drug.
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.
Chemical Problems, 2020
The paper deals with water swollen and pH environment-sensitive hydrogels by means of stitching of poly-Nvinylpyrrolidone with average molecular weight 10 kDa and N,N`-methylene-bis-acrylamide by 1-20% (mass). Hydrogel`s swelling degree and kinetics and their structures were characterized by FTIR, NMR, SEM and TGA methods. Also, some mechanical, biocompatible and mucoadhesive properties of hydrogels were determined. Besides, hydrogels were immobilized by means of doxorubicin as a model preparation and various mathematical models of zero and first order, as well as laws of Korsmeyer-Peppas and Hixson-Crowell were applied to its release profile. Note that the drug proceeded in line with non-Fickian diffusion mechanism while the releaee profile is best fitted with the Higuchi square root model.
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 Applied Polymer Science, 2010
Temperature sensitive polymer network porous hydrogels were developed with N-Isopropylacrylamide (NIPAAm) and AMPS (2-acrylamido-2-methyl-1-propanesulfonicacid), as well as with sucrose as porogen by crosslinking with hydrophilic crosslinker N,N1-methylenebisacrylamide (MBA). The temperature responsive behaviour, the swelling/deswelling kinetics of the hydrogels were investigated. The structural and morphological characterizations of the developed hydrogels were obtained from FTIR spectroscopy and scanning electron microscopy (SEM). The increment in the lower critical solution temperature (LCST) of NIPAAm hydrogels can be done with the help of AMPS and it is confirmed with differential scanning calorimetry (DSC) as well as temperature dependent swelling curves. The model cancer chemotherapy drug Doxorubicin (Dox) was loaded into theses hydrogels and the release studies as well as the released profiles of the drug showed that more than 8–54% of the loaded drug was released in the first half-an-hour at a buffer solution of 7.4 and the rest of the drug was released slowly. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Objective(s): Nowadays hydrogels are one of the upcoming classes of polymer-based controlled-release drug delivery systems. Temperature and pH-responsive delivery systems have drawn much attention because some diseases reveal themselves by a change in temperature and/or pH. The objective of this work is to prepare and characterize composite membrane using responsive nanoparticles into a polymer matrix. Materials and Methods: These nanoparticles were made of the copolymer poly (N-isopropylacrylamide-comethaçrylic acid) by an aqueous dispersion polymerization process and are responsible for dual sensitivity to temperature and pH. Morphology study with SEM, swelling behavior with Dynamic Light Scattering Technique, in vitro drug release behavior with side-by-side Diffusion Cells were also investigated in this paper. Doxorubicin hydrochloride was used as a model solute. Results: The study on the release of doxorubicin hydrochloride showed that the release rate was higher at pH 5 than pH 7.4, increased with the increase of temperature. Nevertheless, ionic strength only poses a minor direct effect at higher pH. Conclusion: Such system may be potentially used as a tumor-targeting doxorubicin hydrochloride delivery in the body.
Advanced Science Letters, 2012
The objective of this study is to utilize the pH sensitivity of modified mesoporous silica nanoparticles (MSN) for oral drug delivery. In the first time, a pH-sensitive ionic liquid was synthesized through the quaternization of 3-aminopropyltrimethoxysilane (3-ATMS) with sodium monochloroacetate (SMCA). Then, silica nanoparticle was modified by this pH-sensitive ionic liquid and converted to a pH-sensitive positive-charge silica nanoparticle (PCSN). The nanoparticle was characterized by FTIR and SEM. Naproxen as anionic drug molecules was entrapped in this pH-sensitive positive-charge silica nanoparticles (PCSN) and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4).
Utilization of a sol–gel method for encapsulation of doxorubicin
Journal of Biomaterials Science, Polymer Edition, 2004
The sol-gel pre-doping method was used to encapsulate doxorubicin in silica gels and optimum conditions of preparation of drug-loaded gel were established, ensuring both reproducible and effective results of quantitative encapsulation of doxorubicin and its gradual but complete release. Doxorubicin was encapsulated in polysiloxane polymers using the method based on solgel encapsulation without a catalyst, with an acid catalyst (HCl) and a base catalyst (NH 3 ). The time of gelation of the gel loaded with doxorubicin, encapsulation ef ciency of the drug and the degree of release of the drug from the gel are all affected by the kind of catalyst (acidic or basic) or its absence at the gel preparation stage, and the temperature of the gelation process. The time of sol gelation when using the NH 3 or HCl catalyst was 9 days at 21 ± C, 2 days at 30 ± C and 1.5 days at 37 ± C, while for the gel prepared without a catalyst it was 90 days at 21 ± C, 75 days at 30 ± C and 70 days at 37 ± C. The ef ciency of doxorubicin encapsulation was 99:5 § 0:5% (w/w) for acid-catalyzed gel, 98:9 § 1:01% (w/w) for base-catalyzed gel and 86:4 § 11:6% (w/w) for non-catalyzed gel. A 100% (w/w) release of doxorubicin by diffusion through pores was found only in the case of base-catalyzed gel after a 140-h incubation time. For acid-catalyzed gel and non-catalyzed gel, the total amounts of released doxorubicin after 140 h of incubation were 3-5% (w/w) and 9-11% (w/w), respectively. The stability of doxorubicin encapsulated in the three kinds of gel matrices was found to be improved compared to the stability of a free form of the drug in solution.
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.