Assessment of temperature-sensitive properties of ionically crosslinked sodium alginate/hydroxypropyl cellulose blend microspheres: preparation, characterization, and in vitro release of paracetamol.

Today, polymer systems can be formed to respond to single stimuli or multiple stimuli by changing their properties. The use of these systems, which are designed to be sensitive to stimuli, is expanding in a wide range of applications. Herein, microspheres of sodium alginate (NaAlg) and hydroxypropyl cellulose (HPC) sensitive to dual stimuli for the controlled release of model drug paracetamol were produced by the ionotropic gelation method in the presence of Zn2+ ions. FTIR, DSC, TGA, SEM, and particle size measurements were used to describe the blend microspheres. Low critical solution temperatures (LCST) of polymer blends at different ratios were determined and the biggest change according to the LCST value of HPC was found to be approximately 1-2 °C lower than 41 °C in microspheres with a NaAlg/HPC ratio of 50/50. In vitro release experiments of paracetamol from microspheres were carried out in a gastrointestinal tract simulation environment at two different temperatures (37 °C and 47 °C). From the release profiles, paracetamol release varied depending on the NaAlg/HPC ratio, the paracetamol content in the microspheres, the exposure time to Zn2+ ions, and the pH of the medium. Among the microsphere formulations, the highest entrapment efficiency was 57.86%, obtained for B7 formulation microspheres with a NaAlg/HPC ratio of 70/30, a paracetamol loading percentage of 20%, and a crosslinking time of 5 min.RESEARCH HIGHLIGHTSMicrospheres of sodium alginate (NaAlg) and hydroxypropyl cellulose (HPC) sensitive to dual stimuli for the controlled release of model drug paracetamol were produced by the ionotropic gelation method in the presence of Zn2+ ions.LCST values of the microspheres with a NaAlg/HPC ratio of 50/50 were significantly lower by 1-2 °C than the LCST value of HPC, and the release results supported the temperature sensitivity of the microspheres.Among the microsphere formulations, the highest entrapment efficiency was 57.86% obtained for B7 formulation microspheres.These microspheres can be used as a temperature-sensitive drug delivery system in the biomedical field and also as an encapsulation system of cancer drugs for cancer treatment modalities such as hyperthermia.

Synergistic effect of ZnO nanoparticles and hesperidin on the antibacterial properties of chitosan.

In this study, hesperidin (HSP) biological agent, which has strong antioxidant properties, was successfully transferred to ZnO nanoparticles, which were first synthesized by the hydrothermal method. Then, chitosan (CS)/ZnO-HSP nanocomposites were produced by adding different ratios of the ZnO-HSPs to the biodegradable CS biopolymer by hydrothermal method. The resulting materials were characterized using various biophysical strategies, including X-ray diffraction (XRD), Fourier transform infrared spectrometry, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy. The mean particle size of ZnO was estimated to be 29 nm from the XRD calculations and SEM measurements. The effect of the ZnO-HSPs on the thermal properties of pure CS was investigated by thermogravimetric analysis and differential scanning calorimetry techniques, and improvements were noted in the thermal properties of CS. While the Tg value of CS was 81 °C, this value increased by 13-94 °C with the addition of 6 wt% by weight of the ZnO-HSP. The antibacterial effect of materials was determined by the disc diffusion method. The ZnO-HSPs added to the CS caused the nanocomposites to have a remarkable effect against Escherichia coli and Staphylococcus aureus microorganisms. While the inhibition diameter of the CS against E. coli was 18.3, the same value increased to 22.3 for the composite containing 6 wt% the ZnO-HSP. The HSP increased the antioxidant capacity of both the ZnO-HSP particles and the CS/ZnO-HSP nanocomposites, reducing the toxic effects of ZnO nanoparticles. Thus, it was determined that the CS/ZnO-HSP nanocomposites did not have any cytotoxicity in healthy human cells. The fact that the produced nanocomposites exhibit antibacterial activity and do not harm human cells shows that they can be a safe product for health. From all these results, this triple hybrid system is hoped that it will be used in biomedical applications as a naturally-sourced, environmentally friendly, and cost-effective composite biomaterial by combining its antimicrobial and strong antioxidant properties.

Synthesis and characterization of temperature-sensitive microspheres based on acrylamide grafted hydroxypropyl cellulose and chitosan for the controlled release of amoxicillin trihydrate.

This study deals with the preparation of temperature-sensitive chitosan/hydroxypropyl cellulose-graft-polyacrylamide (CS/HPC-g-PAAm) blend microspheres as a controlled drug release system. For this purpose, HPC-g-PAAm copolymers of hydroxypropyl cellulose (HPC) with acrylamide (AAm) were synthesized using cerium (IV) ammonium nitrate as initiator. The HPC-g-PAAm copolymers were characterized by using Fourier transform infrared spectroscopy (FTIR), elemental analysis, and differential scanning calorimetry (DSC). Lower critical solution temperatures (LCST) of the synthesized copolymers were determined. Temperature-sensitive blend microspheres of HPC-g-PAAm and chitosan were prepared by emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker in the hydrochloric acid catalyst (HCl) and they were used to achieve controlled release of amoxicillin trihydrate (AMX), an antibiotic drug. The microspheres were characterized by DSC, X-ray diffraction (X-RD), and FTIR spectroscopy. In addition, surfaces of empty and drug-loaded microspheres were examined by scanning electron microscopy (SEM). The effects of variables such as CS/HPC-g-PAAm ratio, drug/polymer ratio, amount of cross-linker, and reaction time of grafting on AMX release were investigated at three different pH environments (1.2, 6.8, 7.4) at 25 °C, 37 °C, and 50 °C. The release results showed that the microspheres had temperature sensitivity and the AMX release was slightly more controlled by especially increasing graft yield (%).

Development and optimization of Fe3+-crosslinked sodium alginate-methylcellulose semi-interpenetrating polymer network beads for controlled release of ibuprofen.

In this study, ionically crosslinked beads of sodium alginate (NaAlg) and methylcellulose (MC) were prepared as semi-interpenetrating polymer networks (semi-IPN) in the size range of 1.97 ± 0.09-1.22 ± 0.13 mm by crosslinking with FeCl3 and loaded with ibuprofen (IBU), which is a nonsteroidal anti-inflammatory drug. The highest 93.33% entrapment efficiency of IBU was achieved, and the drug release behaviors, mean particle size, and entrapment efficiency of beads were investigated in terms of the polymer composition, a ratio of ibuprofen to polymer, exposure time to crosslinker, and concentration of the crosslinking agent. Semi-IPN formulations prepared were also characterized using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray Diffraction (X-RD), and scanning electron microscopy (SEM). It was observed that IBU-loaded beads displayed better release performance with an increase amount of NaAlg in the structure. Finally, the optimum IBU release was obtained as 93.9% for beads containing 66.7% (w/w) NaAlg, 33.3% (w/w) MC, IBU/polymer ratio of 1/4, FeCl3 concentration of 0.1 M, and crosslinking time of 90 min. The in vitro release rate was fitted to five empirical equations, and the diffusion exponent n, which indicated that the release mechanism of IBU from beads followed the Anomalous and Case II transport mechanism.

Flurbiprofen-loaded interpenetrating polymer network beads based on alginate, polyvinyl alcohol and methylcellulose: design, characterization and in-vitro evaluation.

The main objective of this study was to develop an appropriate interpenetrating polymer network (IPN) particulate system from water-soluble polymers such as sodium alginate (NaAlg), poly (vinyl alcohol) (PVA) and methyl cellulose (MC) for the controlled release of flurbiprofen (FBP), a non-steroidal anti-inflammatory drug. Therefore, polymeric IPN beads containing FBP were prepared by crosslinking with glutaraldehyde (GA) as the crosslinking agent and by varying experimental variables such as polymer ratio, crosslinking time and drug/polymer ratio. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were used to characterize the IPN beads. They were also evaluated with bead diameter, equilibrium swelling degrees, entrapment efficiencies and release profiles. It was observed that the release of FBP from beads was influenced by variables such as NaAlg amount in polymer matrix, crosslinking time and FBP/polymer ratio, and release mechanism of FBP from IPN beads followed non-Fickian transport. As a result of the studies, the highest drug release at the end of 6 h was observed in IPN beads with NaAlg/PVA/MC ratio of 4/1/1, FBP/polymer ratio of 1/4 and crosslinking time of 15 and 30 min.

Novel ionically crosslinked acrylamide-grafted poly(vinyl alcohol)/sodium alginate/sodium carboxymethyl cellulose pH-sensitive microspheres for delivery of Alzheimer's drug donepezil hydrochloride: Preparation and optimization of release conditions.

In this work, the graft copolymer, poly(vinyl alcohol)-grafted polyacrylamide (PVA-g-PAAm), was synthesized and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and elemental analysis. Microspheres of PVA-g-PAAm/sodium alginate (NaAlg)/sodium carboxymethyl cellulose (NaCMC) were prepared by the emulsion-crosslinking method and used for the delivery of an Alzheimer's drug, donepezil hydrochloride (DP). The release of DP increased with the increase in drug/polymer ratio (d/p) and PVA-g-PAAm/NaAlg/NaCMC ratio, while it decreased with the increase in the extent of crosslinking. The optimum DP release was obtained as 92.9% for a PVA-g-PAAm/NaAlg/NaCMC ratio of 1/2/1, d/p ratio of 1/8, and FeCl3 concentration of 7% (w/v).

Controlled delivery of the popular nonsteroidal anti-inflammatory drug, paracetamol, from chitosan-g-polyacrylamide microspheres prepared by the emulsion crosslinking technique.

In this paper, chitosan-graft-polyacrylamide (CS-g-PAAm) microspheres as drug delivery matrices of paracetamol were prepared by the emulsion crosslinking technique, using glutaraldehyde (GA) as a crosslinker. Graft copolymer of chitosan with acrylamide was synthesized using cerium (IV) ammonium nitrate (CAN). The microspheres formed had average particle sizes in the range of 78-252 µm. Paracetamol entrapment efficiency was found to vary between 31.89% and 72.61%, as determined by UV spectroscopy. Drug release in acidic and phosphate buffer solutions (pH 1.2 and 7.4) of the CS-g-PAAm microspheres was influenced by formulation factors such as the concentration of CS-g-PAAm, the paracetamol/polymer ratio (w/w), and the amount of crosslinker.

Ibuprofen microencapsulation within acrylamide-grafted chitosan and methylcellulose interpenetrating polymer network microspheres: Synthesis, characterization, and release studies.

This study deals with the development of interpenetrating polymer network (IPN) microspheres of acrylamide (AAm) grafted onto a chitosan (CS) backbone and methylcellulose (MC). Chitosan-graft-polyacrylamide (CS-g-PAAm) was synthesized by cerium (IV) ammonium nitrate-induced free radical graft polymerization. The grafting percentage was found to be 50.58%. The synthesized graft copolymer and MC were used to prepare microspheres by the water-in-oil (w/o) emulsion-crosslinking method, and crosslinked with glutaraldehyde (GA) as drug delivery matrices of ibuprofen (IBU). The release of IBU from microspheres decreased when the amount of CS-g-PAAm in the polymer matrix and amount of crosslinker added were increased, while it increased with the increase of the IBU/polymer ratio.