Scientia Pharmaceutica

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) with antipyretic, analgesic, and anti-inflammatory activity; however, its low aqueous solubility limits its dissolution rate and, consequently, its oral bioavailability. This study aimed to develop and physicochemically characterize an ibuprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) using a Box–Behnken experimental design. Fifteen formulations were prepared and evaluated based on CQAs: cloud point, robustness to dilution, self-emulsification time, droplet size, zeta potential, and polydispersity index (PDI). The experimental responses were subjected to statistical analysis; robustness to dilution as the only response yielding a statistically valid and predictive model within the studied design space, which was used as the sole optimization criterion. The optimal formulation was evaluated and characterized according to previously established CQAs and subjected to thermodynamic stability testing and stress testing over one month. The optimized formulation exhibited rapid self-emulsification, with a self-emulsification time of 37.02 s, a cloud point of 64.87 °C, and high robustness to dilution across different pH conditions and dilution volumes. Moreover, it exhibited a mean droplet size below 157 nm, a zeta potential of −15.43 ± 0.58 mV, and a PDI of 0.251, suggesting adequate colloidal stability and uniformity of the dispersed system. These physicochemical attributes support the potential of the developed system as a platform for further biopharmaceutical evaluation of ibuprofen oral delivery.

Multidrug resistance (MDR) has become a major global health threat, leading to the emergence of difficult-to-treat bacterial “superbugs” among both Gram-positive and Gram-negative species. In hospital settings, biofilm (BF)-producing staphylococci further aggravate this problem by markedly increasing tolerance to conventional antibiotics, thereby promoting chronic and potentially life-threatening infections. In the present study, previously synthesized and characterized 1,12-bis-triphenyl phosphonium dodecane bromide nanovesicles (BPPB, 45 nm, water) were assayed by DLS in a medium (TSB), which was used for microbiologic tests, to assess the actual particle size (≈65 nm) existing in this biological setting, with PDI (0.37) and zeta potential (+6.1 mV). Although never investigated for its effects on the formation of staphylococcal BF, BPPB was, for the first time, evaluated as a potential novel agent to combat its development. A total of 12 highly BF-producing isolates from our collection, comprising six Staphylococcus aureus and six S. epidermidis strains, were selected because they are strong BF producers. Their full antibiogram was determined, and they were tested against BPPB to determine minimum inhibitory concentrations (MICs). Subsequently, BF inhibition activity was evaluated at ½ MIC, MIC, and 2× MIC concentrations. Vancomycin (V), used as a reference antibiotic, was tested under the same experimental conditions. BPPB exhibited MIC values ranging from 0.125 to 0.250 µg/mL, which were 1–8-fold lower than those of V. V did not inhibit BF formation by S. epidermidis at all and inhibited BF formation by Bam and Aam S. aureus isolates (96–97% inhibition) only at max concentrations (2 × MIC). Conversely, BPPB demonstrated potent and consistent inhibition activity against all strains, irrespective of species or resistance profile, as determined by VITEK. BF inhibition values of 83–99%, 95–>99%, and 98–>99% were observed at ½ MIC, MIC, and 2 × MIC, respectively. To confirm that BF inhibition did not arise from killing bacteria, determinations of bacterial colony count after BPPB treatment at 4 × MIC for 24 h were performed, establishing full vitality and a regrowth of 45% with respect to the inoculum. Once reseeded as in the control, treated bacteria grew exactly as the control. Overall, the findings confirmed the nanosized dimension of BPPB particles, which remained <100 nm, including in the complex biological medium; this highlighted the strong BF-forming capability and MDR phenotype of the selected staphylococcal isolates, as well as the remarkable antibacterial and BF inhibition efficacy of BPPB nanovesicles, significantly outperforming vancomycin. Importantly, the low cytotoxicity previously observed against eukaryotic Cos-7 and HepG2 cells, resulting in high selectivity index (SI) values (23.0–90.5), supports BPPB as a promising candidate for the development of new NM-based therapeutic strategies against MDR staphylococcal BF-associated infections.

Compounds isolated from the macroalga Caulerpa sertularioides have been reported to exhibit cytotoxic activity. The objective of this study was to assess the antioxidant effects of compounds isolated from C. sertularioides as well as their antiproliferative effect against cancerous cell lines and to elucidate their chemical structure. The antiproliferative activity of C. sertularioides extracts was evaluated using the MTT standard assay in cancerous and non-cancerous cell lines. Morphological changes were observed via fluorescence microscopy, and the chemical structure of bioactive compounds was determined by nuclear magnetic resonance. Antioxidant activity was assessed using ABTS and DPPH methods. Among all extracts, the acetone extract exhibited the highest antioxidant activity (IC₅₀ of 27.3 ± 6.1 μg/mL) in the ABTS assay, which classifies it as a very potent antioxidant. Among the tested extracts, the hexane extract showed the strongest antiproliferative activity in breast (MDA-MB-231) and cervical cancer (HeLa) cell lines. The most active fraction (F15), obtained by open-column chromatography of hexane extract, exhibited the highest bioactivity against the MDA-MB-231 cell line (IC₅₀ of 55 ± 3.1 µg/mL); these cells exhibited morphological changes consistent with apoptosis. NMR analysis revealed signals tentatively assigned to 1-monolinolein, glycerol, bis(2-ethylhexyl) phthalate and bis(2-ethylhexyl) terephthalate. These findings support the potential of C. sertularioides as a source of bioactive compounds with antioxidant and antiproliferative properties.