Synthesis and Characterization of Acrylamide/Acrylic Acid Co-Polymers and Glutaraldehyde Crosslinked pH-Sensitive Hydrogels

This project aims to synthesize and characterize the pH-sensitive controlled release of 5-fluorouracil (5-FU) loaded hydrogels (5-FULH) by polymerization of acrylamide (AM) and acrylic acid (AA) in the presence of glutaraldehyde (GA) as a crosslinker with ammonium persulphate as an initiator. The formulation’s code is named according to acrylamide (A1, A2, A3), acrylic acid (B1, B2, B3) and glutaraldehyde (C1, C2, C3). The optimized formulations were exposed to various physicochemical tests, namely swelling, diffusion, porosity, sol gel analysis, and attenuated total reflection-Fourier transform infrared (ATR-FTIR). These 5-FULH were subjected to kinetic models for drug release data. The 5-FU were shown to be soluble in distilled water and phosphate buffer media at pH 7.4, and sparingly soluble in an acidic media at pH 1.2. The ATR-FTIR data confirmed that the 5-FU have no interaction with other ingredients. The lowest dynamic (0.98 ± 0.04% to 1.90 ± 0.03%; 1.65 ± 0.01% to 6.88 ± 0.03%) and equilibrium swelling (1.85 ± 0.01% to 6.68 ± 0.03%; 10.12 ± 0.02% to 27.89 ± 0.03%) of formulations was observed at pH 1.2, whereas the higher dynamic (4.33 ± 0.04% to 10.21 ± 0.01%) and equilibrium swelling (22.25 ± 0.03% to 55.48 ± 0.04%) was recorded at pH 7.4. These findings clearly indicated that the synthesized 5-FULH have potential swelling characteristics in pH 6.8 that will enhance the drug’s release in the same pH medium. The porosity values of formulated 5-FULH range from 34% to 62% with different weight ratios of AM, AA, and GA. The gel fractions data showed variations ranging from 74 ± 0.4% (A1) to 94 ± 0.2% (B3). However, formulation A1 reported the highest 24 ± 0.1% and B3 the lowest 09 ± 0.3% sol fractions rate among the formulations. Around 20% drug release from the 5-FULH was found at 1 h in an acidic media (pH1.2), whereas >65% of drug release (pH7.4) was observed at around 25 h. These findings concluded that GA crosslinked 5-FU loaded AM and AA based hydrogels would be a potential pH-sensitive oral controlled colon drug delivery carrier.

Novel Synthesis, Characterization and Amoxicillin Release Study of pH-Sensitive Nanosilica/Poly(acrylic acid) Macroporous Hydrogel with High Swelling

The effect of SiO2 nanoparticles on the formation of PAA (poly acrylic acid) gel structure was investigated with seeded emulsion polymerization method used to prepare SiO2/PAA nanoparticles. The morphologies of the nanocomposite nanoparticles were studied by transmission electron microscopy (TEM). Fourier-transform infrared (FTIR) spectroscopy results indicated that the PAA was chemically bonded to the surface of the SiO2 nanoparticles. Additionally, the resulting morphology of the nanocomposite nanoparticles confirmed the co-crosslinking role of the SiO2 nanoparticles in the formation of the 3D structure and hydrogel of PAA. SiO2/PAA nanocomposite hydrogels were synthesized by in situ solution polymerization with and without toluene. The morphology studies by field emission scanning electron microscopy (FESEM) showed that when the toluene was used as a pore forming agent in the polymerization process, a macroporous hydrogel structure was achieved. The pH-sensitive swelling behaviors of the nanocomposite hydrogels showed that the formation of pores in the gels structure was a dominant factor on the water absorption capacity. In the current research the absorption capacity was changed from about 500 to 4000 g water/g dry hydrogel. Finally, the macroporous nanocomposite hydrogel sample was tested as an amoxicillin release system in buffer solutions with pHs of 3, 7.2, and 9 at 37 °C. The results showed that the percentage cumulative release of amoxicillin from the hydrogels was higher in neutral and basic mediums than in the acidic medium and the amoxicillin release rate was decreased with increasing pH. Additionally, the release results were very similar to swelling results and hence amoxicillin release was a swelling controlled-release system.

Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats

Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate absence seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics in the WAG/Rij rat, an established rodent model of absence epilepsy, we demonstrate that absence seizures are highly sensitive to arterial carbon dioxide, suggesting that seizure-generating circuits are sensitive to pH. Moreover, hyperventilation consistently activated neurons within the intralaminar nuclei of the thalamus, a structure implicated in seizure generation. We show that intralaminar thalamus also contains pH-sensitive neurons. Collectively, these observations suggest that hyperventilation activates pH-sensitive neurons of the intralaminar nuclei to provoke absence seizures.