Background/Objectives: Alginate nanoparticles (NPs) are commonly synthesised using either an emulsion technique that involves organic solvent use or ionotropic gelation utilising multivalent cations, e.g., Ca⁺². However, the extensive use of organic solvents imposes detrimental effects on the ecosystem, and using multivalent cations as crosslinkers could eventually lead to the leakage of these cations, thus disrupting nanoparticle matrices. Therefore, this study aimed to overcome the limitations of these techniques by eliminating the usage of organic solvents and multivalent cations. Methods: In this research, alginate nanoparticles were synthesised using proton gelation by microfluidic technology through protonating alginate carboxylate groups to crosslink alginate chains through H-bond formation. Results: The prepared acid-gelled alginate nanoparticles demonstrated an MHD circa 200 nm and a PDI of less than 0.4 at pH 0.75. Moreover, 5-FU was successfully encapsulated into acid-gelled alginate nanoparticles and displayed a high EE% of around 30%, comparable to the EE% at high alginate concentration and molecular weight (0.4 H-ALG) achieved by Ca⁺²-crosslinked alginate nanoparticles; however, 5-FU NPs had superior characteristics, i.e., a lower MHD (around 500 nm) and PDI (<0.5). The optimum formula (0.4 H-ALG) was explored at various pH values, i.e., low pH of 4.5 and high pH of 10, and alginate NPs produced by acid gelation demonstrated high stability in terms of MHD and PDI, with slight changes at different pH values, indicating stable crosslinking of alginate matrices prepared by technology compared with Ca⁺²-crosslinked alginate NPs. Conclusions: In conclusion, this research has invented an ecologically friendly approach to producing acid-gelled alginate nanoparticles with superior characteristics compared with the conventional methods, and they could be harnessed as nanocarriers for therapeutics delivery (5-FU). Also, this research offers a promising approach for developing eco-friendly and biocompatible drug carriers. The produced nanoparticles have the potential to enhance drug stability, improve controlled release, and minimise toxic effects, making them suitable for pharmaceutical applications.

Objective: Propolis is highly recommended in aphthous stomatitis, a condition that requires a proper delivery tool to achieve an efficient treatment. For this indication, a buccal patch that provides prolonged mucosal contact and protection would be beneficial. Accordingly, in this study, we designed propolis-loaded buccal patches, composed of three polymers (alginate, carboxymethylcellulose, and polyvinylpyrrolidone) of complementary properties, and the proper combination of them to produce the patch of optimum properties. Material and Method: Nine patches of different polymer ratios were prepared by casting method and evaluated by assessing their swelling, adhesion time and strength, and dissolution rate. Then the patches properties were correlated using artificial neural network analysis. Result and Discussion: The results showed that all patches were smooth, translucent, and flexible with surface pH between 6.5 and 7.4. The correlation between polymer composition and measured properties was complex and non-linear. Therefore, an artificial neural network was used to analyze these properties and optimize them. The model of this analysis provides higher weights for favorable tensile and adhesion strengths while considering swelling, rigidity, and fast dissolution rate as unfavorable. According to summation analysis, the combination of CMC% and PVP% of 15.5 and 13, respectively, provides the best score of 3.5.

[This corrects the article DOI: 10.1016/j.ijpx.2019.100036.].

Infectious diseases are a leading cause of death globally. While beta-lactam antibiotics remain highly effective treatments, their efficacy is increasingly threatened by microbial beta-lactamase, an enzyme that deactivates these vital drugs. This escalating antimicrobial resistance has been widely reported internationally. Beta-lactamase inhibitors (BLIs), like clavulanic acid, are co-administered with beta-lactams to mitigate this resistance. However, these inhibitors themselves are becoming susceptible to similar resistance mechanisms. This necessitates the urgent discovery of innovative compounds with potent anti-beta-lactamase activities. This study leveraged in silico docking to design and synthesize novel N,N'-diaroyl-4,4'-methylenedianiline monocyclic azetidinone compounds (which resist the Beta-lactamase hydrolysis). Our docking efforts guided the synthesis of ten new compounds, created by reacting selected acid chlorides with synthesized Schiff bases to form the azetidinone ring. We characterized the structures of these synthesized compounds using physical and spectral data. We then biologically tested the monobactam compounds, determining their Minimum Inhibitory Concentration (MIC) against three strains of beta-lactamase-producing Gram-negative bacteria. Their anti-beta-lactamase activities were subsequently compared to clavulanic acid, used as a co-inhibitor with amoxicillin against the same bacterial strains using disk diffusion method. Our results indicate that all synthesized monobactam compounds exhibited beta-lactamase inhibitory actions. Notably, their activity against Pseudomonas aeruginosa and Escherichia coli was stronger than against Klebsiella pneumoniae. The compounds Az2, Az3, Az6, and Az8 having the stronger activities, they representing 14- and 17-mm inhibition zones (moderate activities) against Pseudomonas aeruginosa and Escherichia coli respectively. While all compounds demonstrated varying degrees of anti-beta-lactamase activity, their potency remained lower than that of the standard, clavulanic acid. Notably, chloride substituents showed promising results. these electronegative atoms facilitate stronger interactions with the enzyme's active sites. The nitro groups and halogen atoms appear to enhance the binding of hydrophobic residues within the beta-lactamase active site, thereby strengthening the overall interaction. This study underscores the critical importance of developing new beta-lactamase inhibitors to overcome the pervasive challenge of bacterial resistance.