Poly(vinyl alcohol)-induced thixotropy of an l-carnosine-based cytocompatible, tripeptidic hydrogel (original) (raw)
Related papers
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 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.
Indian Journal of Pharmaceutical Education and Research
In this study, Poly (HEMA/Acrylamide/ Itaconic acid) (HAI) polymer was synthesized for using in the release of Doxorubicin drug. Poly (HEMA/acrylamide/Itaconic acid) (HAI) hydrogel was prepared by a radical addition reaction in aqueous media formed by HEMA, acrylamide, Itaconic acid, in the presence of TEMED (N,N,N',N'-tetramethylenediamine). The characterization of the polymer was performed by FTIR analysis. At the same time, swelling and drug absorption capabilities of the polymers were analyzed. It has been observed that the entire drug, which was added to the solution with 0.1 mg of polymer, was absorbed in around 25 hours. This measurement showed that the absorption of this polymer is quite high compared to many polymers in the literature. Moreover, this polymer showed 80% swelling at 1000 minutes. In the light of these results, it has been concluded that this new polymer is very suitable for the release of Doxorubicin drug.
Click-cross-linked, doxorubicin-loaded hydrogels based on poly(styrene-alt-maleic anhydride)
Express Polymer Letters, 2020
A hydrogel is a cross-linked three-dimensional product of macromolecular hydrophilic networks. Due to their unique properties, hydrogels have been extensively studied for tissue engineering, especially, they have excellent biocompatibility and the capability to be the type of drug delivery system [1, 2]. The high water content provides them with properties similar to natural extracellular matrixes. The risk of the drug denaturation and aggregation due to exposure to an organic solvent can be minimized by hydrogels. The internal network makes hydrogels have solid-like properties. Hydrogel networks may be physical gels or chemical gels. Physical gels form through physical interactions, while chemical gels are held together by covalent bonds. Chemical gel methods for making the internal network have made significant progress so far. Click chemistry, one of the methods, provided hydrogels with moderately high mechanical properties [3-6] and was also useful in biomedical engineering [7-12]. The emerging studies in click chemistry have generated 'metal-free' reactions. One example of interesting metal-free click chemistry is the inverse 248
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.
Synthesis and evaluation of water soluble pH sensitive poly (vinyl alcohol)-doxorubicin conjugates
Journal of biomaterials science. Polymer edition, 2018
The accuracy of spatiotemporal control cargo delivery and release are primordial to enhance the therapeutic efficiency and decrease the undesirable effects, in this context a novel prodrug were developed based on biocompatible polyvinyl alcohol (PVA) substrate. PVA was conjugated to doxorubicin (PVA-DOX) via an acid-labile hydrazone linkage. PVA was first functionalized with acidic groups, then reacted with hydrazine hydrate to form an amide bond. The amine group of PVA hydrazide was linked to carbonyl group (C = O) of DOX to form a pH sensitive hydrazone bond. The molecular structure of the PVA-DOX was confirmed by FTIR, XPS, and H-NMR analysis methods. The degree of grafting were evaluated by TGA and confirmed by XPS, which reveals the successful bond attachment of DOX to PVA. Our findings confirm pH dependent DOX release from PVA-DOX prodrug with faster release rate in acidic environment (pH 5.0, pH 6.0) and slower release rate in neutral pH environment (pH 7.4). Compared to the ...
pH Triggered Injectable Amphiphilic Hydrogel Containing Doxorubicin and Paclitaxel
International Journal of …, 2011
Injectable hydrogel with hydrophobic microdomains for incorporating both hydrophilic and hydrophobic drugs, herein doxorubicin hydrochloride (DOX) and paclitaxel (PTX), was synthesized through dynamic bonding of glycol chitosan and benzaldehyde capped poly(ethylene glycol)-block-poly(propylene glycol)block-poly(ethylene glycol) via Schiff's reaction triggered by environmental pH. Rheology tests show that the inclusion of hydrophilic drug decreases the gelation time and gains more robust gel, while the addition of hydrophobic drug has opposite influences. Dual-drug release from the DOX + PTX loaded gels was observed and the release rate can be accelerated by decreasing the environmental pH from physiological (7.4) to weak acidic pH (6.8). In vivo investigation proved that the gels were able to diminish the amount of DOX in blood circulation and limit the DOX-induced cardiotoxicity. By intratumoral administration, the hydrogel-drug formulations resulted in efficient growth inhibition of subcutaneous tumor (B16F10) on C57LB/6 mouse model. The advantage of the current system for DOX + PTX combination therapy was demonstrated by a prolongation of survival time in comparison with the single drug therapy.
Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release capability
International Journal of Pharmaceutics, 2006
The influence of the proportion of acrylamidomethyl-␥-cyclodextrin (␥-CD-NMA) on loading and release of the hydrophobic triamcinolone acetonide (TA) and the hydrophilic propranolol (PR) by acrylic acid hydrogels was evaluated. ␥-CD-NMA was synthesized by condensation of ␥-cyclodextrin (␥-CD) with N-(hydroxymethyl) acrylamide. Hydrogels were prepared with ␥-CD-NMA and sodium acrylate (3 M or 4 M), using N,N-methylen(bisacrylamide) (BIS) as cross-linker, by free radical polymerization into glass moulds of 2 mm wide and were cut as discs (10 mm diameter). ␥-CD-NMA did not modify the pH-dependent swelling of the hydrogels, but significantly increased the swelling degree in the 40:60 ethanol:water, medium in which TA can be dissolved. Hydrogels prepared with ␥-CD-NMA above 5% (w/w of total monomers) showed a remarkably higher capacity to load TA, e.g., 33 mg/g dry hydrogel versus 0.6 mg/g dry hydrogel without ␥-CD-NMA. This is explained by the formation of 1:1 inclusion complexes of TA with ␥-CD mers that overcomes the lack of interactions with the acrylic groups of the network. The release of TA in water, 0.1 N HCl, or pH 6.8 phosphate buffer was sustained for at least 24 h, whatever the pH and the composition of the medium used. In contrast, loading of PR from the water solutions was greater for hydrogels prepared with 3 M acrylate than with 4 M acrylate, irrespective to their content in ␥-CD-NMA, and in less than 2 h ca. 80% PR was released. The lower affinity of PR for the ␥-CD cavities, compared to the strong intensity of the electrostatic interactions with the acrylic acid groups, explains why the incorporation of ␥-CD-NMA did not increased the loading and control release capacity of the hydrogels of this hydrophilic drug. In summary, the copolymerisation of CD with acrylic monomers can provide highly hydrophilic pH-sensitive networks which load large amounts of hydrophobic drugs and release them in a sustained way.
ACS Applied Bio Materials, 2020
Dynamic G-quadruplex hydrogel is engineered by using guanosine, 2-formylphenylboronic acid and 4-Arm PEG-NH 2. The gelation conditions are optimized by varying concentrations of the gelators, pH and different alkali metal ions. The formation of imino-boronate bonds during the gelation process is fully characterized with FT-IR, 1 H NMR and 11 B NMR spectroscopy. The secondary supramolecular G-quadruplex structure and the formation of nanofibrillar morphology are well examined using several spectroscopic and microscopic techniques. The mechanical strength of the hydrogel is investigated by rheological experiments. The hydrogel is injectable and self-healable due to dynamic nature of the imono-boronate bonds. The dynamic bonds provide distinct shear-thinning and thixotropic properties to the resulting hydrogel with almost 90% recovery of its mechanical strength after 4 cycles. The pH responsive behavior of the hydrogel is achieved by pH sensitive imino-boronate bonds, which are unstable at acidic pH. To investigate the biocompatibility of the hydrogel, a wide range of hydrogel concentrations are examined by in vitro cell culture experiments using MCF-7 cell line. After biocompatibility test of the hydrogel, the anticancer drug doxorubicin is incorporated inside the gel to analyze the drug release profile at different pHs. The release rate of the loaded drug is observed faster in lower pH (pH 4.8) than in physiological pH (pH 7.4). Different release rate of the drug from the drug loaded hydrogel in different pHs is driven by the pH sensitive imino-boronate bonds. The release profiles of the drug follow zero order kinetics due to slow degradation of the hydrogel.
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.