Unravelling pH/pKa influence on pH-responsive drug carriers: Insights from ibuprofen-silica interactions and comparative analysis with carbon nanotubes, sulfasalazine, and alendronate.

This study employs density functional theory to explore the interaction between ibuprofen (IBU) and silica, emphasizing the influence of the trimethylsilyl (TMS) functional group for designing pH-responsive drug carriers. The surface (S) and drug (D) molecules' neutral (0) or deprotonated (-1) states were taken into consideration during the investigation. The likelihood of these states was determined based on the pKa values and the desired pH conditions. To calculate the pH-dependent interaction energy (EintpH), four different situations have been identified: S0D0, S0D-1, S-1D0, and S-1D-1.The electrostatic component of interaction energy aligns favorably with its theoretical value in both the Debye-Hückel and Grahame models. The investigation has gathered first-hand experimental data on the drug loading and release of pH-responsive mesoporous silica nanoparticles. Effective drug loading was observed in the acidic environment of the stomach (pH 2-5), followed by a release in the slightly basic to neutral pH of the small intestine (pH 7.4), These findings align with existing literature. The results revealed horizontal drug adherence on silica surfaces, improving binding capabilities. Comparisons were made with combinations involving carboxylated carbon nanotubes and ibuprofen, silica, and sulfasalazine, and silica and alendronate, exploring drug loading/release dynamics associated with positive/negative interaction energies. The investigation, supported by experimental data, contributes valuable insights into pH-responsive mesoporous silica nanoparticles, offering new design possibilities for drug carriers.

Theoretical insights and implications of pH-dependent drug delivery systems using silica and carbon nanotube.

In this paper we have studied the density functional theory of four drugs ibuprofen, alendronate, Sulfasalazine and paracetamol with quartz, propylamine, trimethylamine functionalized quartz and carboxyl modified carbon nanotube. The attractive and repulsive interaction energies between drugs and quartz is obtained at various pH values. The attractive and repulsive energies are well correlated with experimental drug loading and releasing behavior by mesoporous silica nanoparticles. Further, a theoretical model is developed that accounts the electrostatic interaction between silica and drug and the model can predict the drug loading and releasing behavior by silica nanoparticles at various pH values. Sulfasalazine can be taken orally and loaded with trimethyl ammonium functionalized mesoporous silica nanoparticles, which keeps the drug in tact with the carrier in the acidic environment of the stomach and releases it into the neutral or basic medium of the small intestine. Alendronate may be loaded and released from propylamine functionalized mesoporous silica nanoparticles in the ranges of 1-5 and > 8, respectively. Ibuprofen is absorbed in an acidic environment and released in basic conditions for carboxyl modified carbon nanotube. The loading and releasing pH ranges for paracetamol in trimethylammonium functionalized mesoporous silica nanoparticles are 4-8 and >8, respectively. We also convert the pH-dependent variant of the diffusion-controlled Higuchi equation. We have changed the original Higuchi equation to produce the pH-dependent variation by incorporating the Nernst-Planck equation into Flick's first law. The updated equation could be used to forecast when medication particles with varying release times will emerge from a nanoparticles matrix.

Plasma Bead Entrapped Liposomes as a Potential Drug Delivery System to Combat Fungal Infections.

Fibrin-based systems offer promises in drug and gene delivery as well as tissue engineering. We established earlier a fibrin-based plasma beads (PB) system as an efficient carrier of drugs and antigens. In the present work, attempts were made to further improve its therapeutic efficacy exploiting innovative ideas, including the use of plasma alginate composite matrices, proteolytic inhibitors, cross linkers, and dual entrapment in various liposomal formulations. In vitro efficacy of the different formulations was examined. Pharmacokinetics of the formulations encapsulating Amphotericin B (AmpB), an antifungal compound, were investigated in Swiss albino mice. While administration of the free AmpB led to its rapid elimination (<72 h), PB/liposome-PB systems were significantly effective in sustaining AmpB release in the circulation (>144 h) and its gradual accumulation in the vital organs, also compared to the liposomal formulations alone. Interestingly, the slow release of AmpB from PB was unusual compared to other small molecules in our earlier findings, suggesting strong interaction with plasma proteins. Molecular interaction studies of bovine serum albumin constituting approximately 60% of plasma with AmpB using isothermal titration calorimetry and in silico docking verify these interactions, explaining the slow release of AmpB entrapped in PB alone. The above findings suggest that PB/liposome-PB could be used as safe and effective delivery systems to combat fungal infections in humans.

Porcine parvovirus VP1/VP2 on a time series epitope mapping: exploring the effects of high hydrostatic pressure on the immune recognition of antigens.

Porcine parvovirus (PPV) is a DNA virus that causes reproductive failure in gilts and sows, resulting in embryonic and fetal losses worldwide. Epitope mapping of PPV is important for developing new vaccines. In this study, we used spot synthesis analysis for epitope mapping of the capsid proteins of PPV (NADL-2 strain) and correlated the findings with predictive data from immunoinformatics. The virus was exposed to three conditions prior to inoculation in pigs: native (untreated), high hydrostatic pressure (350 MPa for 1 h) at room temperature and high hydrostatic pressure (350 MPa for 1 h) at - 18 °C, and was compared with a commercial vaccine produced using inactivated PPV. The screening of serum samples detected 44 positive spots corresponding to 20 antigenic sites. Each type of inoculated antigen elicited a distinct epitope set. In silico prediction located linear and discontinuous epitopes in B cells that coincided with several epitopes detected in spot synthesis of sera from pigs that received different preparations of inoculum. The conditions tested elicited antibodies against the VP1/VP2 antigen that differed in relation to the response time and the profile of structurally available regions that were recognized.

Synergism between high hydrostatic pressure and glutaraldehyde for the inactivation of Staphylococcus aureus at moderate temperature.

The sterilization of transplant and medical devices should be effective but not detrimental to the structural properties of the materials used. In this study, we examined the effectiveness of chemical and physical agents for inactivating Staphylococcus aureus, a gram-positive bacterium and important cause of infections and biofilm production. The treatment conditions in this work were chosen to facilitate their subsequent use with sensitive materials. The effects of temperature, high hydrostatic pressure, and glutaraldehyde disinfectant on the growth of two strains of S. aureus (ATCC 25923 and BEC 9393) were investigated individually and/or in combinations. A low concentration of glutaraldehyde (0.5 mM), high hydrostatic pressure (300 MPa for 10 min), and moderate temperature (50 °C), when used in combination, significantly potentiated the inactivation of both bacterial strains by > 8 orders of magnitude. Transmission electron microscopy revealed structural damage and changes in area that correlated with the use of pressure in the presence of glutaraldehyde at room temperature in both strains. Biofilm from strain ATCC 25923 was particularly susceptible to inactivation. The conditions used here provided effective sterilization that can be applied to sensitive surgical devices and biomaterials, with negligible damage. The use of this experimental approach to investigate other pathogens could lead to the adoption of this procedure for sterilizing sensitive materials.