Tetracycline hydrochloride loaded-alginate based nanoparticle-hydrogel beads for potential wound healing applications: In vitro drug delivery, release kinetics, and antibacterial activity.

Novel hydrogel beads based on nanocomposite with outstanding antibacterial and swelling capabilities have been successfully produced as an efficient drug carrier for potential drug delivery systems in wound healing applications. The beads were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and EDX-Mapping analysis. Then, using tetracycline hydrochloride (TCH) as a model drug system, they were studied in vitro for their potential efficiency as pH and temperature dependent sustained drug delivery carriers. Moreover, they were assessed in terms of porosity, swelling degree, encapsulation efficiency, and in vitro release kinetics. Beads released drugs at their highest levels under alkaline circumstances (pH = 8) and at a temperature of 39 °C, with a cumulative TCH release of 96.2 % at 36 h and in accordance with the Weibull kinetics model (R2 = 0.98). Additionally, the disc diffusion experiment demonstrated the strong antibacterial activity of the synthesized beads and offered a feasible and cost-effective wound dressing material for treating infected wounds.

Magnetic nanocomposite through coating mannose-functionalized metal-organic framework with biopolymeric pectin hydrogel beads: A potential targeted anticancer oral delivery system.

This study designed magnetic nanocomposite hydrogel beads for a potential targeted anticancer oral delivery system. To end this, nanohybrids of Fe3O4/MIL-88(Fe) (FM) were synthesized through in-situ method by the treatment of terephthalic acid (TPA) and (Fe(NO3)3·9H2O) in the presence of Fe3O4 nanoparticles. They were then modified with mannose sugar as an anticancer receptor to achieve a targeted drug delivery system. After loading methotrexate (MTX), they were coated with pH-sensitive pectin hydrogel beads in the presence of a calcium chloride crosslinker for possible transferring the nanohybrids to the intestine through the acidic environment of the digestive system. The results of different analysis techniques showed that the materials were properly synthesized, coated, and loaded. The designed magnetic nanocomposite hydrogel beads showed pH-sensitive swelling and drug release rate, protecting MTX from the acidic environment of the stomach. MTT test revealed a good cytotoxicity toward colon cancer HT29 cell lines. Remarkably, the functionalization of MTX-loaded FM nanohybrids with mannose (MTX-MFM) enhanced their anticancer properties up to about 20 %. The results recommended that the prepared novel magnetic nanocomposite hydrogel beads have a good potential to be used as a targeted anticancer oral delivery system.

Ultrasound-assisted adsorption of chlorpyrifos from aqueous solutions using magnetic chitosan/graphene quantum dot­iron oxide nanocomposite hydrogel beads in batch adsorption column and fixed bed.

Chlorpyrifos is a hazardous material that pollutes the environment and also poses risks to human health. Thus, it is necessary to remove chlorpyrifos from aqueous media. In this study, chitosan-based hydrogel beads with different content of iron oxide-graphene quantum dots were synthesized and used for the ultrasonic-assisted removal of chlorpyrifos from wastewater. The results of batch adsorption experiments showed that among the hydrogel beads-based nanocomposites, the chitosan/graphene quantum dot­iron oxide (10) indicated a higher adsorption efficiency of about 99.997 % at optimum conditions of the response surface method. Fitting the experimental equilibrium data to different models shows that the adsorption of chlorpyrifos is well described by the Jossens, Avrami, and double exponential models. Furthermore, for the first time, the study of the ultrasonic effect on the removal performance of chlorpyrifos showed that the ultrasonic-assisted removal of chlorpyrifos significantly reduces the equilibration time. It is expected that the ultrasonic-assisted removal strategy can be a new method to develop highly efficient adsorbents for rapid removal of pollutants in wastewater. Also, the results of the fixed bed adsorption column showed that the breakthrough time and exhausting time of chitosan/graphene quantum dot­iron oxide (10) were equal to 485 and 1099 min, respectively. And finally, the adsorption-desorption study showed the successful reuse of adsorbent for chlorpyrifos adsorption in seven runs without a significant decrease in adsorption efficiency. Therefore, it can be said that the adsorbent has a high economic and functional potential for industrial applications.

Preparation and characterization of magnetic nanohydrogel based on chitosan for 5-fluorouracil drug delivery and kinetic study.

Chemotherapy is currently used for most cancer treatments, but one of the significant problems of this treatment is that it affects the healthy tissues of the body. Therefore, designing new systems for the intelligent and controlled release of these drugs in cancer tissues is one of the major challenges in the world. Hence, today, huge costs are spent designing appropriate new drug delivery systems (DDS) with controlled drug release. In this study, chitosan-polyacrylic acid encapsulated Fe3O4 magnetic nanogelic core-shell (Fe3O4@CS-PAA) was synthesized in the presence of glutaraldehyde used for loaded anticancer 5-fluorouracil (5-FU) drug. Also, the prepared Fe3O4@CS-PAA was characterized by using FT-IR, SEM, XRD, and VSM analysis. Then, drug delivery tests were carried out in the in-vitro conditions that are the simulated physiological environment and tumor tissue conditions. The drug release tests indicated that the Fe3O4@CS-PAA upgraded the rate of 5-FU release from nanogelic core-shell under tumor tissue conditions (pH 4.5) than physiological environments (pH 7.4). In addition, various models were used to investigate the drug release mechanism. Results of modeling studies of drug release showed the mechanism of 5-FU release from Fe3O4@CS-PAA controlled by Fickian diffusion.

Development of novel aptasensor for ultra-sensitive detection of myoglobin via electrochemical signal amplification of methylene blue using poly (styrene)-block-poly (acrylic acid) amphiphilic copolymer.

Amplification of electrochemical signal in order to betterment of limit of detection in determination of biomarkers has an important role in early detection of some dangerous diseases such as cancers. For this purpose, in this research, two types of poly (styrene)-block-poly (acrylic acid) amphiphilic copolymer (PS61-b-PAA596 and PS596-b-PAA61) were synthesized by controlled radical polymerization method via reversible addition-fragmentation chain transfer polymerization (RAFT) technique. Chemical structure of block copolymers was confirmed by FT-IR spectroscopy and their surface morphology was assessed by scanning electron microscopy (SEM). Self-assembly of these block copolymers into polymeric vesicles (polymersomes), loading and release efficiency of methylene blue as an electroactive indicator were investigated in DMF and THF solvents. On the basis of our findings PS61-b-PAA596 has better capability for loading and release of MB than PS596-b-PAA61. Then the obtained methylene blue-loaded polymersome successfully used for development of an aptasensor toward determination of trace amounts of myoglobin. The proposed aptasensor showed a wide linear range from 1.0 aM to 1.0 µM with an ultra-low detection limit of 0.73 aM. Applying this amplification strategy, determination of myoglobin in real samples was successfully performed.

Synthesis of chitosan-grafted poly-acrylic acid (CTS-g-PAA) hydrogel and its potential application in biosensors for signal enhancing and bioanalysis.

Nowadays, hydrogels have been attracted a lot of interest due to their immense potential in different fields such as biomedicine and biotechnology. Biodegradable and biocompatible pH-sensitive chitosan-grafted polyacrylic acid (CTS-g-PAA) hydrogel was synthesized by grafting an acrylic acid monomer onto chitosan at the presence of methylene bisacrylamide as a cross-linking agent and ammonium persulphate as an initiator. FT-IR spectroscopy and scanning electron microscopy (SEM) were used to analyze the properties of the obtained hydrogel. The synthesized hydrogel is suitable for the delivery of many hydrophilic drugs or species. Using a multi-walled carbon nanotube modified-glassy carbon electrode (CNT-GCE), the loading and release conditions of Nile Blue (NB) as an electroactive compound were evaluated utilizing the differential pulse voltammetry (DPV) and cyclic voltammetry (CV). The effect of various parameters on the electrochemical signal of NB was investigated, and the optimal conditions for the efficient performance of hydrogel to delivery of NB were obtained. The electrocatalytic current values show linear dependence to NB concentration in the range of 0.098 - 0.971 µM while the detection limit of this electrochemical platform was 12.3 nM. The unique proposed hydrogel with the electroactive NB has a broad range of possible applications in biosensors for signal enhancement and bioanalysis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10854-021-06939-7.

5­Fluorouracil loaded chitosan/polyacrylic acid/Fe3O4 magnetic nanocomposite hydrogel as a potential anticancer drug delivery system.

In most cancer treatments, chemotherapy is currently necessary; hence, more attention was devoted to developing new methods for designing drug delivery systems (DDS) with controlled drug release. For this aim, anticancer 5­fluorouracil (5-FU) drug was loaded into chitosan/polyacrylic acid/Fe3O4 magnetic nanocomposite hydrogel (CS/PAA/Fe3O4) through immersing in the drug solution. The prepared CS/PAA/Fe3O4 was characterized using FT-IR, XRD, VSM, TGA and SEM analysis. For demonstrating the efficiency of the prepared novel nanocomposite carrier as a controlled DDS, in-vitro the drug delivery tests were carried out in mimicking the colon and rectal conditions. The drug release tests showed that the CS/PAA/Fe3O4 enhanced the stability of drug dosing for a long time with controlled releases in the colon and rectal conditions. According to the obtained results, the prepared nanocomposite hydrogel could potentially to be used in DDS as a colon and rectal administration of 5-FU.

Investigation of aqueous stability of taxol in different release media.

In the present study, the aqueous stability of taxol in different aqueous media and immiscible aqueous/organic systems at 37 °C was investigated. The aqueous media included phosphate buffered saline (PBS) and PBS containing 10% methanol, 10% ethanol, 10% hydroxypropyl ß-cyclodextrin (HP-ßCD), 1% sodium citrate and 1% Tween 80. The immiscible systems consisted of PBS/octanol, PBS/dichloromethane, PBS/chloroform and PBS/ethyl acetate. The concentrations of taxol and related derivatives in each of the media were determined through the high-performance liquid chromatography assay. Results showed that hydrolysis and epimerization were two major types of degradation for taxol in the aqueous media starting from the initial hours of contact (6 hours). Addition of Tween 80 to PBS moderately increased the aqueous stability of taxol. As well, using PBS containing 10% HP-ßCD inhibited the taxol hydrolysis, while epimerization still in process. In the case of immiscible systems, except for PBS/ethyl acetate system, no evidences of taxol hydrolysis were observed. Meanwhile, epimerization of taxol in PBS/dichloromethane and PBS/chloroform systems underwent due to the ability of C-Cl bonds to form hydrogen bonding with the hydroxyl group of C7 of taxol.