Poly(vinyl alcohol)-induced thixotropy of an l-carnosine-based cytocompatible, tripeptidic hydrogel (original) (raw)
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.
New Formulations of Polysaccharide-Based Hydrogels for Drug Release and Tissue Engineering
Gels, 2015
Polysaccharide-based hydrogels are very promising materials for a wide range of medical applications, ranging from tissue engineering to controlled drug delivery for local therapy. The most interesting property of this class of materials is the ability to be injected without any alteration of their chemical, mechanical and biological properties, by taking advantage of their thixotropic behavior. It is possible to modulate the rheological and chemical-physical properties of polysaccharide hydrogels by varying the cross-linking agents and exploiting their thixotropic behavior. We present here an overview of our synthetic strategies and applications of innovative polysaccharide-based hydrogels: hyaluronan-based hydrogel and new derivatives of carboxymethylcellulose have been used as matrices in the field of tissue engineering; while guar gum-based hydrogel and hybrid magnetic hydrogels, have been used as promising systems for targeted controlled drug release. Moreover, a new class of materials, interpenetrating hydrogels (IPH), have been obtained by mixing various native thixotropic hydrogels.
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.
Journal of Controlled Release, 2011
Topotecan (TPT) Camptothecin (CPT) Injectable hydrogel Local chemotherapy Anticancer Drug-material interaction Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) hydrogels were tried as implants to encapsulate antitumor drug topotecan (TPT), a derivative of camptothecin (CPT). Despite of water solubility of TPT, the in vitro release of this lowmolecular-weight drug from hydrogels sustained for 5 days with only a mild initial burst. The antitumor efficacy of the released TPT was further validated in S180-bearing mice. Surprisingly, the fraction of the active lactone form of TPT was increased to above 50% in the hydrogel matrix, while the fraction was just about 10% in phosphate buffer saline under physiological pH at 37°C. This significant effect was interpreted not by the local acidic pH within the hydrogel, but by the increase of pK a of the carboxylate group of the open-ring form due to the hydrophobic interaction between the amphiphilic polymer and TPT. Theoretical analysis via a pK a -related mechanism was also performed, which was consistent with our experimental measurements. Hence, this study has revealed that an appropriate biomaterial could, via drug-material interactions, enhance the drug efficacy by increasing the active fraction of some drugs which exhibit a reversible conversion between the active and inactive structures.
Controlled release of doxorubicin from pH-responsive microgels
Acta Biomaterialia, 2013
Stimuli-responsive hydrogels have enormous potential in drug delivery applications. They can be used for site-specific drug delivery due to environmental variables in the body such as pH and temperature. In this study, we have developed pH-responsive microgels for the delivery of doxorubicin (DOX) in order to optimize its anti-tumor activity while minimizing its systemic toxicity. We used a copolymer of oligo(polyethylene glycol) fumarate (OPF) and sodium methacrylate (SMA) to fabricate the pH-responsive microgels. We demonstrated that the microgels were negatively charged, and the amounts of charge on the microgels were correlated with the SMA concentration in their formulation. The resulting microgels exhibited sensitivity to the pH and ionic strength of the surrounding environment. We demonstrated that DOX was efficiently loaded into the microgels and released in a controlled fashion via an ionexchange mechanism. Our data revealed that the DOX release was influenced by the pH and ionic strength of the solution. Moreover, we designed a phenomenological mathematical model, based on a stretched exponential function, to quantitatively analyze the cumulative release of DOX. We found a linear correlation between the maximum release of DOX calculated from the model and the SMA concentration in the microgel formulation. The anti-tumor activity of the released DOX was assessed using a human chordoma cell line. Our data revealed that OPF-SMA microgels prolonged the cell killing effect of DOX.
Journal of Applied Polymer Science, 2013
ABSTRACTPoly(vinyl alcohol) (PVA) hydrogels containing drug–β‐cyclodextrin inclusion complexes (ICs) were synthesized with glutaraldehyde (GA) as a crosslinker. The role of cyclodextrin (CD), the effect of the nature of drug, and the degree of crosslinking on the drug‐release process were investigated. The probable mechanism of drug release was also explored. Controlled release of the drug was achieved from the hydrogels containing the ICs. The nature of the drug, in terms of its binding efficacy with CD, played an important role. The effect of the degree of crosslinking on the release pattern was strikingly different from that in the hydrogels containing free drug and those with ICs. The role of CD in the drug‐release process was not only due to its inclusion ability but also its effect on the polymer relaxation. GA, apart from crosslinking PVA, probably interacted with the cyclodextrins and, thereby, influenced the matrix structure and the drug‐release kinetics. © 2013 Wiley Perio...