Triple-Emulsion-Based Antibubbles: A Step Forward in Fabricating Novel Multi-Drug Delivery Systems.

Developing carriers capable of efficiently transporting both hydrophilic and lipophilic payloads is a captivating focus within the pharmaceutical and drug delivery research domain. Antibubbles, constituting an innovative encapsulation system designed for drug delivery purposes, have garnered scientific interest thanks to their distinctive water-in-air-in-water (W1/A/W2) structure. However, in contrast to their precursor, i.e., nanoparticle-stabilized W1/O/W2 double emulsion, traditional antibubbles lack the ability to accommodate a lipophilic payload, as the intermediary (volatile) oil layer of the emulsion is replaced by air during the antibubble fabrication process. Therefore, here, we report the fabrication of triple-emulsion-based antibubbles (O1/W1/A/W2), in which the inner aqueous phase was loaded with a nanoemulsion stabilized by various proteins, including whey, soy, or pea protein isolates. As model drugs, we employed the dyes Nile red in the oil phase and methylene blue in the aqueous phase. The produced antibubbles were characterized regarding their size distribution, entrapment efficiency, and stability. The produced antibubbles demonstrated substantial entrapment efficiencies for both lipophilic (ranging from 80% to 90%) and hydrophilic (ranging from 70% to 82%) components while also exhibiting an appreciable degree of stability during an extended rehydration period of two weeks. The observed variations among different antibubble variants were primarily attributed to differences in protein concentration rather than the type of protein used.

Preparation of acid-responsive antibubbles from CaCO3-based Pickering emulsions.

HYPOTHESIS: Hydrophobized fumed silica particles were previously reported for producing antibubbles that are quite stable in neutral as well as in acidic media. To produce acid-responsive antibubbles (e.g., for gastric drug delivery), the silica nanoparticles must be replaced by suitable particles, e.g., calcium carbonate (CaCO3), which can degrade at low pH to release the encapsulated drug. EXPERIMENTS: Two variants of CaCO3-stabilized antibubbles were prepared (by using CaCO3 particles pre-coated with stearic acid, or by using native CaCO3 particles in combination with sodium stearoyl lactylate) and drug release was compared with classic antibubbles produced with hydrophobized fumed silica particles. FINDINGS: CaCO3 particles (pre-coated with stearic acid) can be used to produce stable antibubbles, which provided an entrapment efficiency of a model drug (methylene blue, MB) of around 85%. A burst release of MB (∼60%) from the antibubbles was observed at pH 2 (i.e., the pH of the stomach), which was further increased to 80% during the next 30 min. On the contrary, at neutral pH, about 70% of the drug remained encapsulated for at least 2 h. We further demonstrated that the acidic conditions led to the desorption of CaCO3 particles from the air-liquid interface resulting in the destabilization of the antibubbles and the release of drug-containing cores.

Advances in antibubble formation and potential applications.

Antibubbles are unusual physical objects consisting of a liquid core(s) surrounded by a thin air film/shell while in a bulk liquid. Antibubbles carry two air-liquid interfaces, i.e., one with the inner liquid and the other with the outer liquid. The distinct structure of antibubbles makes them quite attractive for drug and therapeutic delivery, although their potential applications have not been realized so far. The major challenge in this regard is a short-lived span of antibubbles, which is usually in the order of a few minutes to a few hours based on the stabilization mechanism used. We present a critical overview of different techniques that can be used to generate antibubbles. This includes a more commonly applied conventional approach in which the air-film is created through surface entrapment when a liquid jet/drop falls on a bulk liquid. The other available options rely on entirely different mechanisms for antibubble formation, for instance, through drop encapsulation by a submerged air bubble, or through evaporation/sublimation of volatile oil from a W/O/W double emulsion. Furthermore, the mechanisms of antibubble formation and collapse, and the factors affecting their stability have been discussed explicitly; and wherever required, the concept is correlated to other allied physical objects such as bubbles, liquid marbles, etc. Finally, the potential applications, research gaps in the existing knowledge, and some directions for future research are provided towards the end of this article.

Treatment outcomes, antibiotic use and its resistance pattern among neonatal sepsis patients attending Bahawal Victoria Hospital, Pakistan.

BACKGROUND: Sepsis is one of the major causes of neonatal mortality in Pakistan. This study aimed to investigate the treatment outcomes, antibiotic use and its resistance pattern among neonatal sepsis patients attending a tertiary care hospital in Pakistan. We also aimed to identify the factors affecting mortality in neonatal sepsis patients. METHODS: A descriptive, cross-sectional study was conducted in the pediatric wards of the Bahawal Victoria Hospital, Bahawalpur, Pakistan. All eligible neonatal sepsis patients who were registered at the study site from January 1, 2019 to June 30, 2019 were included in the study. The data collection form included information on patient's characteristics, antibiotic use and its sensitivity pattern, laboratory and microbiological data, and final treatment outcomes. Treatment outcomes included, discharged (with treatment success), leave against medical advice (LAMA), discharged on request (DOR) and death. Multivariable binary logistic regression analysis was used to find the independent factors associated with death. A p-value of less than 0.05 was considered statistically significant. RESULTS: Among the total 586 patients, 398 (67.9%) were male, 328 (56%) were preterm, 415 (70.8%) were diagnosed with early onset sepsis, 299 (51%) were born with low birth weight. Most of the patients (n = 484, 82.6%) were treated with amikacin+cefotaxime at the start of treatment. Culture was positive in 52 (8.9%) patients and the most commonly identified bacteria included, Klebsiella species (n = 19, 36.5%) followed by E. coli (n = 15, 28.5%) and Staphylococcus aureus (n = 8, 15.4%). The identified bacterial isolates showed high level of resistance against the antibiotics initiated at the start of the treatment, while resistance against piperacillin+tazobactam, imipenem, vancomycin and linezolid was very low. Just under half of the patients (n = 280, 47.8%) successfully completed the treatment (i.e., discharged with treatment success), while 123 (21%) patients died during treatment. In multivariable binary logistic regression, the factors which still remained significantly associated with neonatal death included, preterm delivery (AOR 9.59; 95% CI 4.41, 20.84), sub-optimal birth weight (AOR 5.13; 95% CI 2.19, 12.04), early onset sepsis (AOR 2.99; 95% CI 1.39, 6.41) and length of hospital stay (AOR 0.76; 95% CI 0.67, 0.88). CONCLUSION: The mortality rate associated with sepsis was high in our study cohort. The bacterial isolates showed high level of resistance against the antibiotics started as the empiric therapy. Rational use of antibiotics can decrease the adverse outcomes in neonatal sepsis patients.